Multiple algorithms highlight key brain genes driven by multiple anesthetics.

Anesthesia serves as a pivotal tool in modern medicine, creating a transient state of sensory deprivation to ensure a pain-free surgical or medical intervention. While proficient in alleviating pain, anesthesia significantly modulates brain dynamics, metabolic processes, and neural signaling, thereby impairing typical cognitive functions. Furthermore, anesthesia can induce notable impacts such as memory impairment, decreased cognitive function, and diminished intelligence, emphasizing the imperative need to explore the concealed repercussions of anesthesia on individuals. In this investigation, we aggregated gene expression profiles (GSE64617, GSE141242, GSE161322, GSE175894, and GSE178995) from public repositories following second-generation sequencing analysis of various anesthetics. Through scrutinizing post-anesthesia brain tissue gene expression utilizing Gene Set Enrichment Analysis (GSEA), Robust Rank Aggregation (RRA), and Weighted Gene Co-expression Network Analysis (WGCNA), this research aims to pinpoint pivotal genes, pathways, and regulatory networks linked to anesthesia. This undertaking not only enhances comprehension of the physiological changes brought about by anesthesia but also lays the groundwork for future investigations, cultivating new insights and innovative perspectives in medical practice.

The cross-sectional correlation between the oxidative balance score and cardiometabolic risk factors and its potential correlation with longitudinal mortality in patients with cardiometabolic risk factors.

BACKGROUND: This study analyzes the correlation between oxidative balance score (OBS), cardiometabolic risk factors (CMRFs), and mortality in individuals with CMRFs. METHODS: Data were chosen from the National Health and Nutrition Examination Survey. The survey-weighted multivariable logistic regression models were implemented to explore the relationship between OBS and the risk of CMRFs. Then, Cox proportional hazard models were employed to estimate the impact of OBS on mortality in individuals with CMRFs. RESULTS: Following multivariate adjustment, the subjects in the highest quartile exhibited a 46% reduction in the risk of CMRFs, a 33% reduction in the risk of diabetes, a 31% reduction in the risk of hypertension, and a 36% reduction in the risk of hyperlipidemia, compared with those in the lowest quartile. Furthermore, each 1-unit increase in OBS was remarkably negatively correlated with the prevalence of CMRFs, diabetes, hypertension, and hyperlipidemia. The correlation between OBS and CMFRs was found to be mediated by serum γ-glutamyltransferase (GGT) and white blood cells (WBC), and the mediation effect of GGT levels and WBC, accounting for 6.90% and 11.51%, respectively. Lastly, the multivariate Cox regression model revealed that elevated OBS, irrespective of whether it was treated as a categorical or continuous variable, exhibited a significant association with decreased mortality from all causes, cardiovascular disease, and cancer. CONCLUSIONS: An increased OBS might reflect a lower risk of CMRFs and a favorable prognosis for individuals with CMRFs. Moreover, WBC and GGT may play a potential mediating role between OBS and CMRFs.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Prognostic implication of lactic dehydrogenase-to-albumin ratio in critically ill patients with acute kidney injury.

BACKGROUND: No studies have been published on the correlation between lactic dehydrogenase-to-albumin ratio (LAR) and poor prognosis of acute kidney injury (AKI) patients, warranting further research. This analysis sought to investigate the prognostic implication of LAR in critically ill patients with AKI. METHODS: The present study enrolled 11,046 and 5180 adults with AKI from the Medical Information Mart for Intensive Care III (MIMIC III) and MIMIC IV, respectively. Data from MIMIC IV were identified as the training cohort, and those from MIMIC III were identified as the validation cohort. We applied multivariate regression analysis to identify the link between LAR and all-cause mortality. Restricted cubic spline (RCS) was conducted to figure out the correlation between LAR and in-hospital mortality. Furthermore, we carried out stratification analyses to examine if the effects of LAR on in-hospital mortality were consistent across various subclasses. RESULTS: The level of LAR was remarkably higher in the in-hospital non-survivor group (p < 0.001). Furthermore, the increased LAR group presented a remarkably higher rate of in-hospital mortality at AKI stages 1, 2, and 3 compared with the decreased LAR group (all p < 0.001). Multivariate regression analyses exhibited the independent prognostic significance of LAR for all-cause mortality (all p < 0.001). MIMIC III observed concordant results. RCS indicated a non-linear correlation between LAR and in-hospital death (P for non-linearity < 0.001). The relationship between LAR and in-hospital mortality was still significant in patients with various subclasses. CONCLUSIONS: Elevated LAR at admission is a prognostic risk factor for critically ill patients with AKI.

Development and Validation of a Nomogram for Predicting Overall Survival in Patients with Second Primary Small Cell Lung Cancer After Non-Small Cell Lung Cancer: A SEER-Based Study.

Background: Non-small cell lung cancer (NSCLC) survivors are at an increased risk of developing second primary malignancies, such as small cell lung cancer. This paper sought to establish a prognostic nomogram to assess overall survival (OS) in patients with second primary small cell lung cancer (SPSCLC) after NSCLC. Methods: 420 patients who developed SPSCLC after NSCLC were randomly split into the training and validation groups. A nomogram was established by stepwise regression. Area under the curve (AUC) and calibration plots were applied to assess the prognostic performance of the nomogram. Concordance index (C-index), integrated discrimination improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA) were performed to compare the nomogram with the American Joint Committee on Cancer (AJCC) 8th staging system. Survival risk classification was constructed based on the nomogram. Results: Five variables were chosen to construct the nomogram. The AUC showed that it had a satisfactory discrimination ability. All calibration plots displayed good concordance between nomogram and observation. The C-index, IDI, NRI and DCA showed the nomogram was superior to the AJCC 8th staging system. The Kaplan-Meier curves suggested huge differences in prognosis among the three risk groups. Conclusion: This study build a nomogram and risk stratification system for predicting probabilities of OS in patients with SPSCLC after NSCLC, which can help clinicians in individualized survival assessment and treatment decisions.

Nutritional indices at admission are associated with mortality rates of patients in the intensive care unit.

BACKGROUND: Malnutrition is a common occurrence in critically ill patients, and has been related to poor prognosis in various diseases. Here, we assess the prognostic value of malnutrition using nutritional indices in intensive care units (ICU) patients. METHODS: We retrieved information on 2060 patients from the Medical Information Mart for Intensive Care III, and randomized the patients into training and validation cohorts, at a ratio of 7:3. We estimated their nutritional indices using prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) score. Both multivariate regression analysis and the Kaplan-Meier (KM) survival curve were used to examine the prognostic role of nutritional indices in ICU mortality. Then we evaluated the additional predictive significance of each nutritional index beyond the baseline model including conventional risk factors. RESULTS: Multivariate regression analysis revealed that PNI, GNRI, and CONUT were independent predictors of in-hospital and 1-year mortality (all P < 0.001). KM curves showed higher 1-year mortality rates in having nutritional risk patients (PNI ≤ 38 or GNRI ≤ 98 or CONUT ≥ 2). Moreover, subgroup analyses revealed a significant association between each nutritional index and 1-year mortality in patients with different comorbidities. We also observed a pronounced additional impact on the predictive value of 1-year mortality when PNI, GNRI, and CONUT were separately added to the baseline model. The additional role of each nutritional index was further verified in the validation cohort. CONCLUSIONS: Our results revealed that the nutritional indices at admission are significantly correlated with increased mortality rates in ICU adult patients.

[Research of different expressions of microRNA in sinus node, atrial myocardium, and ventricular myocardium of mouse].

OBJECTIVE: To study microRNA (miRNA) involved in the regulation of sinus cell differentiation by comparing sinus node, atrial myocardium, and ventricular myocardium specific miRNA expression profile differences in Kunming mice. METHODS: A total of 180 Kunming mice, aged 60-90 days and weighing 35-45 g, were selected without gender differences after the method of anatomical localization for sinus node had been confirmed by preliminary experiments in another 10 Kunming mice. All the sinus node, atrial myocardium, and ventricular myocardium tissue from 180 mice were dissected and frozen by liquid nitrogen. The structure of tissue was observed by HE staining. Total RNA were extracted and quality-controlled before hybridize with miRNA chip. The chips with miRNA were used to screen specific miRNAs; and correlation analysis of gene function was done. RESULTS: The area of mice sinus node located at juncture of the superior vena cava and the right atrium junction with crista as its longitudinal axis, ranged 2.0 mm x 1.5 mm x 1.0 mm. HE staining showed the sinus cells were less, with no stripes, lightly stained cytoplasm, large and round nucleus, and there were much fibrous connective tissue around cells with a visible sinus node artery. The miRNA microarray results showed that compared with atrial myocardium and ventricular myocardium, there were 39 differentially expressed miRNAs in sinus node, including 12 up-regulated miRNAs and 27 down-regulated miRNAs. Based on the regulatory networks of differential miRNA and target gene, the regulatory miRNA was obtained. CONCLUSION: The differentially expressed miRNA in mice sinus node possibly may be involved in the regulation of sinus cell differentiation.

[Experimental research of recombinant lentivirus mediated hyperpolarization-activated cyclic nucleotide-gated cation channel 4 gene transfecting bone mesenchymal stem cells].

OBJECTIVE: To investigate the feasibility of recombinant lentivirus (LVs) mediated hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) gene transfecting rat bone mesenchymal stem cells (BMSCs) so as to construct the biological pacemaker cells. METHODS: Sprague Dawley rats at the age of 3-5 weeks were selected to isolate and culture BMSCs using modified whole bone marrow adherent culture method. LVs was used as carrier, and enhanced green fluorescent protein (EGFP) as marker to build LVs-HCN4-EGFP virus liquid. The BMSCs at passage 3 were transfected with LVs-HCN4-EGFP virus liquid (experimental group) and LVs-EGFP null virus liquid (control group). Fluorescence microscope was used to observe the green fluorescent protein expression after 24, 48, and 72 hours of transfection; Western blot method was used to detect the HCN4 protein expression. The electrophysiology was used to detect the pacemaker current in the experimental group. RESULTS: After transfection, BMSCs in the experimental group showed normal morphology and good growth; scattered green fluorescence could be seen at 48 hours under fluorescence microscope, with a transfection efficiency of about 10%; the fluorescence expression increased slightly, with the transfection efficiency of 20% to 25% at 72 hours. While no expression of green fluorescence was seen in the control group. Western blot results showed that the same band expression as a relative molecular mass of HCN4 protein were found at 72 hours after transfection in the experimental group, only weak expression of protein band was seen in the control group; the gray value of the experimental group (33.75 +/- 0.41) was significantly higher than that of the control group (23.39 +/- 0.33) (t=17.524, P=0.013). In the experimental group, the pacemaker current was recorded, and it could be blocked by CsCl, in accordance with the characteristics of pacemaker current. CONCLUSION: The recombinant LVs mediated HCN4 gene is successfully transfected into rat BMSCs, and the expression of HCN4 protein and the pacemaker current can be detected.