Genistein attenuates neuroinflammation and oxidative stress and improves cognitive impairment in a rat model of sepsis-associated encephalopathy: potential role of the Nrf2 signaling pathway.

Oxidative stress and inflammation seem to be the main factors responsible for cognitive impairment in sepsis. Genistein (GEN) is claimed to exert many beneficial effects on health, however, its possible effects on brain sepsis remains unclear. Here, we assess the influence and underling mechanisms of GEN on cognitive impairments in cecal ligation and puncture (CLP)-induced septic model. Rats were randomly divided into Sham, Sham + GEN, CLP, CLP + GEN gropus. Rats were treated with GEN (15 mg/kg at 0 and 12 h after CLP, i.p). Twenty-four hours after CLP, protein levels of cytokines, NF-kB and Nrf2, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins, the activities of antioxidant enzymes and the expression of Nrf2-target genes were evaluated in the hippocampus. At 10 days after sepsis induction, behavioral tests were conducted to evaluate cognitive impairment. The results indicate that GEN can enhance survival percentage and improve cognitive function. Genistein administration significantly reduced TNF-α and IL-1ß levels, MPO activity and protein level of NF-kB in the hippocampus of septic rats. Genistein also decreased the levels of oxidative stress parameters (MDA and protein carbonyls) and elevated the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in septic rats. Furthermore, nuclear Nrf2 and the expression of HO-1 and NQO-1 were also elevated by GEN treatment. These findings suggest that GEN improves cognition impairment in septic rats via decreasing inflammatory responses and oxidative stress, and activation of the Nrf2 pathway.

Electroacupuncture alleviates cognitive dysfunction and neuronal pyroptosis in septic mice.

BACKGROUND: Sepsis is defined as organ dysfunction caused by an uncontrolled response to infection and is followed by a high incidence of cognitive dysfunction, which can severely affect patients' quality of life. Previous studies have suggested that electroacupuncture (EA) is protective against sepsis-associated cognitive dysfunction and that pyroptosis plays a vital role in cognitive function. The aim of this study was to investigate the effect of EA on cognition and neuronal pyroptosis in a mouse model of sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) surgery. Mice were randomly divided into three groups (control, CLP and CLP + EA). EA was performed at bilateral ST36 for three consecutive days after the surgery. The 7-day survival rate of each group was observed on the seventh day after the surgery. The Morris water maze (MWM) was used to test cognitive function from the 8th to 12th day after the surgery. We used transmission electron microscopy (TEM) and transferase dUTP nick-end labeling (TUNEL) staining to determine the structural integrity of hippocampal neuronal membranes and the number of surviving neurons in the hippocampal tissues, respectively. Expression of nucleotide-binding domain-like receptor protein 1 (NLRP1), caspase-1 and gasdermin-D (GSDM D) in hippocampal CA1 neurons was detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and caspase-1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the CLP group, 7-day survival rates and cognitive function were significantly improved in the CLP + EA group. After EA treatment, the integrity of the hippocampal CA1 neuronal membrane and mortality of hippocampal neurons were significantly decreased, and expression of NLRP1, caspase-1 and GSDM D was downregulated. CONCLUSION: EA can alleviate cognitive dysfunction and neuronal pyroptosis in septic mice.

Clinical, Laboratory, Radiological, Bronchoscopic, and Outcome Characteristics of Pulmonary Fungal Infection in Children in PICU in Central China: A Case Series.

Objective: Fungal infections are common in pediatric intensive care units (PICUs), but the monitoring methods are limited. This study analyzed the differences in clinical features, diagnosis, and treatment between PICU patients with and without fungal infection. Methods: This retrospective study analyzed PICU patients at the Maternal and Child Health Hospital of Hubei Province diagnosed with severe pneumonia between January 2015 and January 2020. The patients were divided into the fungal (F) and non-fungal (NF) infection groups. Levels of 1,3-beta-D-glucan (BDG) and galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) were analyzed. Chest computed tomography (CT) images were reviewed. Results: A total of 357 patients were included. In the F group, fever, moist rales, coarse rales, shortness of breath, and sepsis were more common (all P < 0.05); PICU time, hospitalization duration, and BDG- and GM-positive rates in serum and BALF were all significantly higher than in the NF group (all P < 0.05). The BDG- and GM-positive rates in serum and BALF were higher in the F than in the NF group (all P < 0.05). The abnormal lymphocyte ratios in serum were higher in the F group (all P < 0.05). Wedge-shaped, patchy, streaky shadows and subpleural reticulation were higher in CT images of the F group (all P < 0.05). Tracheobronchial stenosis was more common in pulmonary fibroscopy results of the F group (P = 0.04). Conclusion: PICU pneumonia patients with fungal infection have specific clinical and laboratory features compared with those without fungal infection, including higher rates of BALF, serum BDG, GM positivity and tracheobronchial stenosis.

Effect of Thiopental on Ischemic Stroke in Rat Brain in Spontaneously Hypertensive Rats.

Motivation and Problem Statement. Thiopental is an anesthetic drug related to the condition of controlling the area of neurological contexts. This study is related to the analysis of effectiveness for the condition of thiopental application on spontaneously hypertensive rats. Methodology. We have evaluated the thiopental induction as the anesthetic agent. The hypertensive rats were selected to administer thiopental in the form of anesthesia. The selection and application of hypertensive strokes are related to the derivation of an inducible model to assess the efficacy for analyzing the ischemic stroke parameters which relate to the human body. We used middle cerebral artery occlusion (MCAO) models related to spontaneous hypertension with the area of examining the complications in ischemic stroke. Results and Conclusion. The study focused on the experimental analysis based on the selection of spontaneously hypertensive rats associated with the incidence of ischemic stroke. Application of thiopental has reported the weak functionality and mechanism on the relaxation of neuronal activity in the case of rat brain. The considered population of the spontaneously hypertensive rats is evaluated based on the condition of effectiveness as well as the duration of the medication effects within the rat brain. Involvement of thiopental in the case of ischemic stroke has provided the area of risk development for high rate of death incidences after occurrence of acute ischemic stroke. A complication in the area of defining neuroprotective actions provides difficulty in drawing an appropriate conclusion of the study.

Diagnostic value of ONSD in sepsis associated encephalopathy of New Zealand rabbits.

OBJECTIVE: The purpose of the present study was to assess whether optic nerve sheath diameter (ONSD) measured by ultrasound could predict brain injury in sepsis associated encephalopathy (SAE). METHODS: A total of 48 male New Zealand White rabbits were used to establish sepsis model. The levels of neuro-specific enolase (NSE), S100B, myeloperoxidase (MPO), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immuno sorbent assay and ONSD were measured before modeling, 6 h, 12 h and 24 h after modeling. Sixteen rabbits were sacrificed for hematoxylin-eosin (HE) staining of brain tissue and the brain water content at above time points. Rabbits demonstrated brain injury by HE staining were included in the SAE group, the others were enrolled in the control group. The correlation between ONSD and MPO, NSE and S100B in the SAE group were analyzed. Receiver operator characteristic curves were generated to analyze the area under the curve (AUC), specificity and sensitivity of ONSD values for SAE. RESULTS: Twenty-nine of 48 rabbits had brain injury, while 19 cases were enrolled in the control group. The level of MPO, NSE, S100B, TNF-α at 6 h, 12 h and 24 h in SAE group were all higher than those of the control group with statistical significance. The ONSD in SAE group increased with time and significantly wider than those in the control group. Correlation analysis revealed that ONSD was positively correlated with MPO, NSE and S100B in the SAE group. The AUCs for the ONSD value in diagnosing SAE at 6 h, 12 h and 24 h were 0.864, 0.957, 0.877, respectively. CONCLUSIONS: Alterations in ONSD strongly correlated with MPO, NSE and S100B among SAE rabbits. Monitoring of ONSD exhibited a high predictive value for SAE.

Propofol Alleviates Neuropathic Pain Induced by Chronic Contractile Injury by Regulating the Spinal glun2b-p38mapkepac1 Pathway.

BACKGROUND: Propofol acts as an intravenous anesthetic cure which is widely used as a therapy for the craniocerebral injury that comprised surgical anesthesia as well as the sedation done in the intensive care units. Propofol is one of the most commonly used and efficient anesthetics where the painful effects are followed by an injection of propofol. In many cases, patients experience pain followed by anxiety, boredom, fear, and even myocardial ischemia. OBJECTIVE: This study was performed to investigate the underlying mechanism of propofol and its effect on regulating spinal glun2b-p38mapkepac1 pathways in chronic contractile injury. Material and Methods. Contractile injury was performed by ligation around the nerve of the thigh region postanesthesia. Rats were divided into three groups to analyze the changes like mechanical allodynia by the paw withdrawal threshold and histopathological analysis for assessing cellular degradation. L4-L6 from the spinal dorsal horns were isolated and harvested for studying protein expression, by the method of western blotting and immunofluorescence analysis. RESULTS: The pain caused due to mechanical allodynia in the paw region was highest at 1 hour postinduction and lasted for three days postinjury. Pain was significantly less in the group receiving propofol when compared with the isoflurane group for the first two hours of injury. In the propofol group, EPAC1, GluN2B, and p38 MAP K were significantly lower. CONCLUSION: In the rat model of induced chronic contractile injury, postsurgery there was a suppression of the GluN2B-p38MAPK/EPAC1 signaling pathway in the propofol group. As the p38MAPK/EPAC pathway has a significant role in the postoperative hyperalgesia, thus our experiment suggests that propofol has analgesic effects.

Molecular Mechanism of Gas Anesthetics on the Invasion, Metastasis, and Chemosensitivity of Osteosarcoma Cells.

BACKGROUND: Osteosarcoma is one of the most prominent bone cancers which has a predominant occurrence in children and adolescents. This study is focused on determining the effects of treatment of gas anesthetics on invasion, metastasis, and chemosensitivity in the progression of osteosarcoma cells. Material and Methods. The biological effects of the common gas anesthetics-desflurane, isoflurane, and sevoflurane-on osteosarcoma cells were studied and compared. The biological assays were performed for analysis of cell migration and proliferation. RESULTS: Isoflurane and sevoflurane have shown significant inhibition in the osteosarcoma cells at clinically relevant concentrations. Desflurane has shown less potent action on cell migration and inhibition. All three gas anesthetics have shown inhibition in cell proliferation. The effective antiproliferative action was at a clinically significant dose. At low millimolar concentrations, cell apoptosis was moderately affected. Drug combination analysis with chemotherapeutic drugs showed relevant inhibition in cell migration. All three agents showed significant augmentation of chemotherapeutic drugs in suppression and inhibition of inducing apoptosis. The antimigration action is likely to affect the PI3K/AKT pathway and IGF-1. CONCLUSION: The study demonstrates the proposed mechanisms of gas anesthetics and their differential effects on osteosarcoma cells and their survival, migration, growth, and chemosensitivity.

Application of neurally adjusted ventilatory assist in ventilator weaning of infants ventilator weaning.

BACKGROUND: To analyze the application of neurally adjusted ventilatory assist in ventilator weaning of infants. METHODS: A total of 25 infants (15 boys and 10 girls) who were mechanically ventilated by PICU in Hubei Maternal and Child Health Hospital were selected as the study subjects. After the improvement of the basic disease, regular spontaneous breathing, and the withdrawal of the ventilator, all the children obtained the electrical activity of the diaphragm (EAdi) signal. Then, each child was given CPAP and NAVA mode mechanical ventilation 1 h before the withdrawal of the ventilator. Each detection index was recorded 30 min after each mode of ventilation. RESULTS: Two of the 25 children were tracheotomized because of respiratory muscle weakness and could not be converted to NAVA mode without the EAdi signal. Hemodynamic indexes were not statistically different between the two groups of CPAP and NAVA. PaCO2 is not significantly different in the two modes, and both were at normal levels. The PIP in NAVA mode is lower than that in CPAP mode (p < .05), and its EAdi signal was correspondingly low. There were significant differences in the peak pressure (Ppeak), mean pressure (Pmean), and compliance and mean arterial pressure (p < .01) between the CPAP and NAVA model ventilation in 23 patients. CONCLUSION: NAVA can significantly improve the coordination of patients. The therapeutic effect of NAVA was better, which was beneficial to the prognosis of patients and had positive application value in the withdrawal of ventilators in patients.

The Diagnostic Value of Plasma miRNA-497, cTnI, FABP3 and GPBB in Pediatric Sepsis Complicated with Myocardial Injury.

OBJECTIVE: To investigate the diagnostic value of plasma miRNA-497, cardiac troponin I (cTnI), fatty acid binding protein 3 (FABP3), glycogen phosphorylase isoenzyme BB (GPBB) in pediatric sepsis complicated with myocardial injury. METHODS: From August 2018 to February 2020, 82 children with sepsis admitted to our hospital and 50 health children who came for physical examination (defined as control group) were enrolled in this study. Children with sepsis and myocardial injury were enrolled in the combined group (n=35), and those without myocardial injury were enrolled in the sepsis group (n=47). General data of three groups were collected, and the levels of miRNA-497, FABP3, GPBB, creatine kinase isoenzyme MB (CK-MB), procalcitonin (PCT), C-reactive protein (CRP), cTnI and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected and the cardiac function was measured. The diagnostic value of plasma miRNA-497, cTnI, FABP3 and GPBB in pediatric sepsis complicated with myocardial injury was analyzed. RESULTS: The infection site of the combined group was not significantly different from that of the sepsis group. The levels of miRNA-497, FABP3, GPBB, CK-MB, PCT, CRP, cTnI, NT-proBNP in the combined group were all higher than those in the sepsis group and the control group (P<0.05), and the left ventricular ejection fraction (LVEF) in the combined group was significantly lower than that in the other two group (P<0.05). The area under the curve (AUC) of the combination of miRNA-497, FABP3, GPBB, and cTnI in the diagnosis of sepsis complicated with myocardial injury was significantly higher than that of CK-MB, PCT, CRP, NT-proBNP alone (P<0.05), but there was no significant difference when compared with miRNA-497, FABP3, GPBB and cTnI alone (P>0.05). When the optimal thresholds of miRNA-497, FABP3, GPBB, and cTnI were set to 2.03, 6.23ng/mL, 4.01ng/mL, 1.23ng/mL, respectively, the sensitivity was 95.65%, 88.89%, 82.61%, 87.50%, respectively; the specificity was 83.33%, 94.12%, 83.33%, 90.91%, respectively; and the accuracy was 91.43%, 91.43%, 82.86%, 88.57%, respectively. Pearson correlation analysis indicating that miRNA-497 was positively correlated with the levels of FABP3, GPBB, and cTnI in the combined group (r=0.821, 0.621, 0.782, P<0.05). CONCLUSION: Plasma miRNA-497, cTnI, FABP3, and GPBB levels were increased in pediatric sepsis complicated with myocardial injury, and their combination had high diagnostic value, which was of great clinical significance for early diagnosis and early treatment of pediatric sepsis complicated with myocardial injury.

Rapid Diagnosis of IPA Relied on Calcofluor White Fluorescence Staining: Two Cases Report.

Invasive pulmonary aspergillosis (IPA) is a serious infectious disease with high mortality. However, the rapid diagnosis of IPA remains difficult since the microbiological evidence is difficult to obtain or time-consuming. Thus, we attempted to rapidly diagnose two pediatric cases with respiratory failure due to IPA via bronchoalveolar lavage fluid with Calcofluor White fluorescence staining, which has rarely been used before.

Hemophagocytic syndrome associated with Mycobacterium bovis in a patient with X-SCID: a case report.

BACKGROUND: Mycobacterium bovis could infect patients with immunodeficiency or immunosuppressive conditions via Bacillus Calmette-Guérin (BCG) vaccination. Tuberculosis-related hemophagocytic syndrome (HPS) is reported, but not HPS caused by Mycobacterium bovis in children. CASE PRESENTATION: A 4-month Chinese boy presented fever and cough. The initial laboratory investigation showed the lymphocyte count of 0.97 × 109/L, which decreased gradually. HPS was diagnosed based on the test results that fulfilled the HLH-2004 criteria. In addition, Mycobacterium tuberculosis complex was detected from his peripheral blood via metagenomic next-generation sequencing (mNGS) and M. bovis was identified by polymerase chain reaction-reverse dot blot (PCR-RDB). Thus, the patient was treated with Isoniazid, Rifampin, and Pyrazinamide, but not improved. However, parents refused to accept further therapy, and was discharged on the day 12 of admission. To confirm the pathogenesis, genetic analysis was performed. Mutation in the interleukin-2 receptor subunit gamma gene: Exon 6: c.854G > A; p. Arg285Gln was detected in the patient and the mother, which could underlie X-linked severe combined immunodeficiency. CONCLUSIONS: A boy with X-SCID was diagnosed with M. bovis-associated HPS, emphasizing that X-SCID should be considered when M. bovis is detected in a male infant with low lymphocyte counts.

Intraoperative Dexmedetomidine Versus Midazolam in Patients Undergoing Peripheral Surgery With Mild Traumatic Brain Injuries: A Retrospective Cohort Analysis.

BACKGROUND: The intra- and postoperative effects of dexmedetomidine are not completely consistent and midazolam/fentanyl is most widely used in peripheral surgeries. The objectives of the study were to evaluate the sedative, analgesic, hemodynamic, anti-inflammatory, and antioxidant effects of dexmedetomidine against midazolam in patients undergoing peripheral surgeries with mild traumatic brain injuries. METHODS: Medical records of patients who underwent peripheral surgeries with mild traumatic brain injury were included in the analysis. Patients received intraoperative midazolam (MDZ cohort, n = 225) or dexmedetomidine (DEX cohort, n = 231). Pre-, intra-, and postoperative characteristics of patients were collected and analyzed. RESULTS: After administration of anesthesia, up to 40 minutes, patients of the MDZ group had lower modified observer's assessment of alertness/sedation score than those of the DEX group (P = .041), but after 40 minutes, patients of the MDZ group had a higher score than those of the DEX group throughout surgeries (P = 0.048). The DEX group has less requirements of postoperative morphine/equivalent doses than the MDZ group (4 ± 1 vs 5 ± 1, P < .0001, q = 18.451). CONCLUSIONS: Intraoperative DEX offers better sedation, postoperative analgesia, and clinical recovery for peripheral surgeries and suppresses inflammatory response. LEVEL OF EVIDENCE: III.