Association between serum albumin creatinine ratio and all-cause mortality in intensive care unit patients with heart failure.

Background: The serum albumin creatinine ratio (sACR) has been established as a potential indicator for heart disease, however, its relationship with prognosis in intensive care unit (ICU) patients with heart failure remains uncertain. This study aimed to investigate the association between sACR levels and all-cause mortality ICU patients with heart failure. Methods: Clinical data from MIMIC-Ⅳ database was utilized for the analysis of ICU patients with heart failure. Patients were categorized into quartiles (Q1-Q4) based on sACR levels. Kaplan-Meier survival analysis and multivariate adjusted Cox regression models were employed to assess the association between sACR levels and mortality outcomes within 365 days. Subgroup analysis was used to evaluate the prognostic impact of sACR across diverse populations. Restricted cubic spline curves and threshold effect analysis were utilized to quantify the dose-response relationship between sACR levels and risk of all-cause mortality. Mediating effects analysis was conducted to present the involvement of albumin and creatinine in the association between sACR and outcomes. Results: The analysis encompassed a cohort of 4,506 patients, with Kaplan-Meier curves indicating that individuals with lower sACR levels exhibited an elevated risk of all-cause mortality (log-rank p < 0.001). Multivariate adjusted Cox regression and subgroup analysis demonstrated that individuals in Q2 [hazard ratio (HR) 0.82, 95%CI 0.71∼0.96], Q3 (HR 0.76, 95%CI 0.64∼0.91) and Q4 (HR 0.62, 95%CI 0.50∼0.76) had a decreased risk of mortality compared to individuals in Q1 (lower levels of sACR) (p for trend < 0.001), and this inverse relationship was consistently observed across various subgroups. Subsequent restricted cubic spline analysis revealed a negative yet nonlinear relationship between sACR and all-cause mortality (p for nonlinear < 0.001), and threshold effect analysis indicated an effect threshold of 3.75. Additionally, mediating effects analysis emphasized that sACR influenced the outcome not only through serum albumin and creatinine pathways, but also through direct mechanisms. Conclusion: The study found that low levels of sACR were independently associated with an increased risk of one-year all-cause mortality in ICU patients with heart failure, with a threshold effect, which could potentially serve as an early warning indicator for high-risk populations.

Glucosamine promotes seizure activity via activation of the PI3K/Akt pathway in epileptic rats.

CONTEXT: Glucosamine is an amino monosaccharide with a small molecular weight and has a protective effect against various neurological diseases including multiple sclerosis and encephalomyelitis. Interestingly, low-dose glucosamine has exhibited anti-epilepsy activity. Recent studies have shown that the activation of the protein kinase B (Akt) signaling pathway may promote epilepsy. Glucosamine can increase the level of Akt phosphorylation in the brain tissue, which may aggravate epilepsy. Hence, we speculate that a higher dose of glucosamine may aggravate epilepsy via AKT signaling. OBJECTIVE: To investigate the effect of glucosamine on the behavior and electrophysiology of epileptic rats through PI3K/Akt pathway. METHODS: Glucose (2.0 g/kg) and glucosamine (0, 0.5, 1.0, and 2.0 g/kg) were added to 2 mL of drinking water, respectively. An acute seizure rat model of lithium-pilocarpine and PTZ-kindling were constructed to observe the effects of different doses of glucosamine on epileptic behavior and hippocampal electrical activity. Meanwhile, the changes in Akt were detected by western blot. RESULTS: Epileptic seizures were induced by a single dose of pilocarpine or PTZ and 2.0 g/kg of glucosamine significantly prolonged the duration and severity of epileptic seizures, enhanced hippocampal electrical activity energy density, and increased phosphorylated AKT levels. A glucosamine dose of 2.0 g/kg also significantly increased the total onset energy density. Furthermore, 2.0 g/kg glucosamine facilitated the development of the chronic PTZ-kindling process. CONCLUSIONS: Glucosamine may exacerbate acute and chronic epileptic seizures via activation of the PI3K/Akt pathway in rats with experimental epilepsy.

Predictors of Outcome in Clinically Diagnosed Viral Encephalitis Patients: A 5-Year Prospective Study.

BACKGROUND: Viral encephalitis is the most common infectious disease of the central nervous system and is associated with high morbidity, mortality, and disability. The objective of this study was to analyze the clinical characteristics, auxiliary examinations, therapeutic management, and outcomes of patients clinically diagnosed with viral encephalitis and identify the outcome predictors. METHODS: We conducted a prospective observational study by collecting information from patients clinically diagnosed with viral encephalitis at the First Affiliated Hospital of Chongqing Medical University and Yongchuan Hospital of Chongqing Medical University from January 2013 to December 2018. Univariate and multivariate analyses were performed to identify factors that influenced good patient outcomes (mRS < 3) and poor patient outcomes (mRS ≥ 3) at discharge. RESULTS: In total, 216 patients were enrolled in the study. The multivariate analysis suggested that the following factors were associated with a poor outcome: Glasgow Coma Scale (GCS) score (OR 0.154, 95% CI (0.078-0.302), and P < 0.001), focal neurological deficits (OR 9.403, 95% CI (1.581-55.928), and P = 0.014), and total length of hospital stay (OR 1.119, 95% CI (1.002-1.250), and P = 0.045). However, neurological intensive care unit (NICU) treatment, status epilepticus, and abnormal electroencephalogram (EEG) findings did not influence the prognosis of patients. CONCLUSION: Our study suggests that low GCS scores at admission, focal neurological deficits at admission, and a prolonged total hospital stay are predictors of a poor outcome at discharge in clinically diagnosed viral encephalitis patients. Whether early and effective neurological rehabilitation can improve the prognosis of viral encephalitis patients with focal neurological deficits remains to be confirmed in further studies.

Prediction and identification of novel HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from endocan.

BACKGROUND: Prediction and identification of cytotoxic T lymphocyte (CTL) epitopes from tumor associated antigens is a crucial step for the development of tumor immunotherapy strategy. Endocan has been identified as antigen overexpressed in various tumors. METHODS: In this experiment, we predicted and identified HLA-A2-restricted CTL epitopes from endocan by using the following procedures. Firstly, we predicted the epitopes from the amino acid sequence of endocan by computer-based methods; Secondly, we determined the affinity of the predicted peptide with HLA-A2.1 molecule by peptide-binding assay; Thirdly, we elicited the primary T cell response against the predicted peptides in vitro; Lastly, we tested the specific CTLs toward endocan and HLA-A2.1 positive target cells. RESULTS: These data demonstrated that peptides of endocan containing residues 4-12 and 9-17 could elicit specific CTLs producing interferon-γ and cytotoxicity. CONCLUSIONS: Therefore, our findings suggested that the predicted peptides were novel HLA-A2.1-restricted CTL epitopes, and might provide promising target for tumor immunotherapy.

Dendritic cells transduced with glioma-expressed antigen 2 recombinant adenovirus induces specific cytotoxic lymphocyte response and anti-tumor effect in mice.

INTRODUCTION: Glioma is an aggressive common cancer with high mortality worldwide. Up to date, the effective medical therapeutical strategy is limited. Numerous previous studies have indicated that glioma-expressed antigen 2 (GLEA2) might be an attractive prognostic glioma biomarker. METHODS: In this experiment, dendritic cells (DCs) transduced with GLEA2 recombinant adenovirus were utilized to generate cytotoxic lymphocytes (CTLs) in vitro. Additionally, trimera mice were immunized with the transduced DCs to generate CTLs in vivo. RESULTS: The data demonstrated that GLEA2 transduced DCs could effectively generate specific CTL response against glioma without lysing autologous lymphocytes. Moreover, GLEA2 transduced DCs significantly attenuated the tumor growth and prolonged the life span of tumor bearing mice. CONCLUSIONS: These findings suggested that DCs transduced with GLEA2 recombinant adenovirus could generate effective CTL mediated anti-tumor response, and might represent insight in glioma therapy.

A novel scoring system to predict the outcomes of adult patients with hypoxic-ischemic encephalopathy.

BACKGROUND: Adult patients with hypoxic-ischemic encephalopathy (HIE) often incur large costs, but their outcomes are poor. Currently, there is lack of a comprehensive quantitative approach to predict patient prognoses. METHODS: A total of 73 adult patients with HIE participated in this prospective, observational study. Clinical assessments, laboratory tests, and electrophysiological examinations were conducted within 3 days after HIE occurred. Logistic regression model was used to identify independent factors associated with patient outcomes. RESULTS: After a 6-month follow-up, 44 (61.1%) patients survived, 28 (38.9%) patients died, and one patient was lost to follow-up. The level of blood calcium and lactate, the presence of electroencephalography reactivity, and Glasgow Coma Scale (GCS) score were significantly associated with the patient's outcome. Based on the regression coefficients from logistic regression analysis, we constructed a scoring system (CEGL; C: calcium, E: EEG reactivity, G: GCS, L: lactate) to predict the possibility of a patient's death. The area under the receiver operating characteristic curve was 0.91 (P < 0.001, 95% CI [0.87-0.95]) with a specificity of 97.7% and a positive predictive value of 97.4%. CONCLUSION: CEGL score can provide clinicians useful information for assessment of patient prognosis within 6 months after HIE.

Low TT4 as a predictor of poor outcomes in severe encephalitis: a multivariate analysis of 94 patients.

BACKGROUND: To investigate the prognostic value of acute thyroid function in patients with severe encephalitis. METHODS: We retrospectively analyzed information from patients with severe encephalitis from June 2012 to June 2017. Using multivariate logistic regression analysis, we examined predictors of poor outcomes in these patients after 6 months. RESULTS: A total of 94 patients with severe encephalitis were included in the study. Univariate analysis showed that patients with good or poor outcomes had significantly different total thyroxine (TT4) (P = 0.012) and free triiodothyronine (FT3) (P = 0.049) levels, mechanical ventilation requirements (P < 0.001), pulmonary infection complications (P = 0.001), lengths of neurological intensive care unit (P = 0.003) and total hospital (P = 0.012) stay, and Acute Physiology and Chronic Health Evaluation (APACHE II) (P = 0.005) and Glasgow Coma Scale (GCS) (P = 0) scores. The results of multivariate analysis suggested the following factors to be associated with a poor outcome: a low TT4 level (OR 0.303, 95% CI 0.100-0.923) and a low GCS score (OR 0.683, 95% CI 0.506-0.923). CONCLUSIONS: Low TT4 has a predictive value for the adverse outcomes of severe encephalitis; further study is needed for verification.

Prognostic value of electroencephalography (EEG) for brain injury after cardiopulmonary resuscitation.

Cardiac arrest (CA) patients can experience neurological sequelae or even death after successful cardiopulmonary resuscitation (CPR) due to cerebral hypoxia- and ischemia-reperfusion-mediated brain injury. Thus, it is important to perform early prognostic evaluations in CA patients. Electroencephalography (EEG) is an important tool for determining the prognosis of hypoxic-ischemic encephalopathy due to its real-time measurement of brain function. Based on EEG, burst suppression, a burst suppression ratio >0.239, periodic discharges, status epilepticus, stimulus-induced rhythmic, periodic or ictal discharges, non-reactive EEG, and the BIS value based on quantitative EEG may be associated with the prognosis of CA after successful CPR. As measures of neural network integrity, the values of small-world characteristics of the neural network derived from EEG patterns have potential applications.

Reduced amount of olfactory receptor neurons in the rat model of depression.

Reduced olfactory sensitivity has been reported in depressive disorder. However, the pathological mechanism is still unclear. The reduced olfactory bulb (OB) volume and reduced hippocampal neurogenesis has been unraveled in major depressive disorder (MDD). However, changes in olfactory epithelium (OE) have not been reported, which might contribute to olfactory deficits in MDD. In the context, we investigated the thickness of OE in a chronic unpredictable mild stress (CUMS) rat model of depression using hematoxylin and eosin (HE) staining. Simultaneously, the basal cells (labeled by nerve growth factor receptor (p75NGFR)), immature olfactory receptor neurons (ORNs) (marked by growth-associated protein 43 (GAP43)) and mature ORNs (labeled by olfactory marker protein (OMP)) in OE were detected by immunohistochemistry. The results showed that the thickness of OE, the number of basal cells, immature ORNs as well as mature ORNs decreased dramatically in the OE of CUMS rats. Those findings indicate that the reduced number of ORNs might induce OE atrophy in CUMS rats and the abnormalities of the OE may be partially responsible for the reduced olfactory sensitivity in MDD.

Altered expression of the small guanosine triphosphatase RhoA in human temporal lobe epilepsy.

The small guanosine triphosphatase RhoA has recently been implicated in the pathogenesis of epilepsy in animals. In this study, we investigated the expression of RhoA in human epilepsy. Brain tissue samples from 40 patients with intractable epilepsy and 14 histologically normal temporal lobes from control patients were used to compare RhoA immunoreactivity using immunohistochemistry, immunofluorescent staining, and western blotting. Immunohistochemical staining and western blot analysis showed that RhoA immunoreactivity was increased in the patient group (p < 0.05). Immunofluorescent staining showed that RhoA was mainly expressed on cell membranes and in the cytoplasm. Our findings demonstrate that upregulation of RhoA immunoreactivity occurs in the brains of patients with intractable epilepsy.

Down-regulation synaptic vesicle protein 2A in the anterior temporal neocortex of patients with intractable epilepsy.

Synaptic vesicle protein 2A (SV2A) involvement has been reported in the animal models of epilepsy. The aim of this study was to investigate the expression of SV2A in human intractable epilepsy (IE) brain tissue. Using immunohistochemistry, immunofluorescence, and Western blot, we detected SV2A expression in tissue samples from the anterior temporal neocortex of 33 patients who had been surgically treated for IE. We compared these tissues with nine histologically normal anterior temporal lobe samples from controls. SV2A immunoreactive staining was 0.1651+/-0.0564 in patient group and 0.2347+/-0.0187 in the control group (p<0.05) using immunohistochemistry, and this finding was consistently observed with Western blot analysis (0.1727 +/- 0.0471 versus 0.3976+/-0.0983, p<0.05). Immunofluorescence staining showed that SV2A was mainly accumulated in neurons. Our findings demonstrate that down-regulation of SV2A is present in patients with temporal lobe epilepsy.