Identification of potential hub genes linked to immune and metabolic alterations in postoperative systemic inflammatory dysregulation.

Background: Postoperative systemic inflammatory dysregulation (PSID) is characterised by strongly interlinked immune and metabolic abnormalities. However, the hub genes responsible for the interconnections between these two systemic alterations remain to be identified. Methods: We analysed differentially expressed genes (DEGs) of individual peripheral blood nucleated cells in patients with PSID (n = 21, CRP > 250 mg/L) and control patients (n = 25, CRP < 75 mg/L) following major abdominal surgery, along with their biological functions. Correlation analyses were conducted to explore the interconnections of immune-related DEGs (irDEGs) and metabolism-related DEGs (mrDEGs). Two methods were used to screen hub genes for irDEGs and mrDEGs: we screened for hub genes among DEGs via 12 algorithms using CytoHubba in Cytoscape, and also screened for hub immune-related and metabolic-related genes using weighted gene co-expression network analysis. The hub genes selected were involved in the interaction between changes in immunity and metabolism in PSID. Finally, we validated our results in mice with PSID to confirm the findings. Results: We identified 512 upregulated and 254 downregulated DEGs in patients with PSID compared with controls. Gene enrichment analysis revealed that DEGs were significantly associated with immune- and metabolism-related biological processes and pathways. Correlation analyses revealed a close association between irDEGs and mrDEGs. Fourteen unique hub genes were identified via 12 screening algorithms using CytoHubba in Cytoscape and via weighted gene co-expression network analysis. Among these, CD28, CD40LG, MAPK14, and S100A12 were identified as hub genes among both immune- and metabolism-related genes; these genes play a critical role in the interaction between alterations in immunity and metabolism in PSID. The experimental results also showed that the expression of these genes was significantly altered in PSID mice. Conclusion: This study identified hub genes associated with immune and metabolic alterations in patients with PSID and hub genes that link these alterations. These findings provide novel insights into the mechanisms underlying immune and metabolic interactions and new targets for clinical treatment can be proposed on this basis.

Automated phenotyping of postoperative delirium-like behaviour in mice reveals the therapeutic efficacy of dexmedetomidine.

Postoperative delirium (POD) is a complicated and harmful clinical syndrome. Traditional behaviour analysis mostly focuses on static parameters. However, animal behaviour is a bottom-up and hierarchical organizational structure composed of time-varying posture dynamics. Spontaneous and task-driven behaviours are used to conduct comprehensive profiling of behavioural data of various aspects of model animals. A machine-learning based method is used to assess the effect of dexmedetomidine. Fourteen statistically different spontaneous behaviours are used to distinguish the non-POD group from the POD group. In the task-driven behaviour, the non-POD group has greater deep versus shallow investigation preference, with no significant preference in the POD group. Hyperactive and hypoactive subtypes can be distinguished through pose evaluation. Dexmedetomidine at a dose of 25 µg kg-1 reduces the severity and incidence of POD. Here we propose a multi-scaled clustering analysis framework that includes pose, behaviour and action sequence evaluation. This may represent the hierarchical dynamics of delirium-like behaviours.

Alterations in smell or taste in individuals infected with SARS-CoV-2 during periods of Omicron variant dominance.

OBJECTIVES: To characterize the prevalence, severity, correlation with initial symptoms, and role of vaccination in patients with COVID-19 with smell or taste alterations (STAs). METHODS: We conducted an observational study of patients infected with SARS-CoV-2 Omicron admitted to three hospitals between May 17 and June 16, 2022. The olfactory and gustatory functions were evaluated using the taste and smell survey and the numerical visual analog scale at two time points. RESULTS: The T1 and T2 time point assessments were completed by 688 and 385 participants, respectively. The prevalence of STAs at two time points was 41.3% vs 42.6%. Furthermore, no difference existed in the severity distribution of taste and smell survey, smell, or taste visual analog scale scores between the groups. Patients with initial symptoms of headache (P = 0.03) and muscle pain (P = 0.04) were more likely to develop STAs, whereas higher education; three-dose vaccination; no symptoms yet; or initial symptoms of cough, throat discomfort, and fever demonstrated protective effects, and the results were statistically significant. CONCLUSION: The prevalence of STAs did not decrease significantly during the Omicron dominance, but the severity was reduced, and vaccination demonstrated a protective effect. In addition, the findings suggest that the presence of STAs is likely to be an important indicator of viral invasion of the nervous system.

Landscape of immune infiltration in entorhinal cortex of patients with Alzheimer's disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and manifests as progressive memory loss and cognitive dysfunction. Neuroinflammation plays an important role in the development of Alzheimer's disease and anti-inflammatory drugs reduce the risk of the disease. However, the immune microenvironment in the brains of patients with Alzheimer's disease remains unclear, and the mechanisms by which anti-inflammatory drugs improve Alzheimer's disease have not been clearly elucidated. This study aimed to provide an overview of the immune cell composition in the entorhinal cortex of patients with Alzheimer's disease based on the transcriptomes and signature genes of different immune cells and to explore potential therapeutic targets based on the relevance of drug targets. Transcriptomics data from the entorhinal cortex tissue, derived from GSE118553, were used to support our study. We compared the immune-related differentially expressed genes (irDEGs) between patients and controls by using the limma R package. The difference in immune cell composition between patients and controls was detected via the xCell algorithm based on the marker genes in immune cells. The correlation between marker genes and immune cells and the interaction between genes and drug targets were evaluated to explore potential therapeutic target genes and drugs. There were 81 irDEGs between patients and controls that participated in several immune-related pathways. xCell analysis showed that most lymphocyte scores decreased in Alzheimer's disease, including CD4+ Tc, CD4+ Te, Th1, natural killer (NK), natural killer T (NKT), pro-B cells, eosinophils, and regulatory T cells, except for Th2 cells. In contrast, most myeloid cell scores increased in patients, except in dendritic cells. They included basophils, mast cells, plasma cells, and macrophages. Correlation analysis suggested that 37 genes were associated with these cells involved in innate immunity, of which eight genes were drug targets. Taken together, these results delineate the profile of the immune components of the entorhinal cortex in Alzheimer's diseases, providing a new perspective on the development and treatment of Alzheimer's disease.

Incidence and Risk Factors for Hypoxia in Deep Sedation of Propofol for Artificial Abortion Patients.

Background: Respiratory depression is a life-threatening adverse effect of deep sedation. This study aimed to investigate the factors related to hypoxia caused by propofol during intravenous anesthesia. Methods: Three hundred and eight patients who underwent painless artificial abortion in the outpatient department of Shanghai Tenth People's Hospital between November 1, 2019 and June 30, 2020 were divided into two groups according to whether the patients experienced hypoxia (SpO2 < 95%). Preoperative anxiety assessments, anesthesia process, and operation-related information of the two groups were analyzed. The univariate analysis results were further incorporated into logistic regression analysis for multivariate analysis to determine the independent risk factors affecting hypoxia. Results: Univariate analysis revealed that body mass index (BMI) (21.80 ± 2.94 vs. 21.01 ± 2.39; P = 0.038, 95% confidence interval (CI) = [-1.54, -0.04]), propofol dose (15.83 ± 3.21 vs. 14.39 ± 3.01; P = 0.002, CI = [-2.34, -0.53]), menopausal days (49.64 ± 6.03 vs. 52.14 ± 5.73; P = 0.004, CI = [0.79, 4.21]), State Anxiety Inventory score (51.19 ± 7.55 vs. 44.49 ± 8.96; P < 0.001, CI = [-9.26, -4.15]), and Self-rating Anxiety Scale score (45.86 ± 9.48 vs. 42.45 ± 9.88; P = 0.021, CI = [-6.30, -0.53]) were statistically significant risk factors for hypoxia during the operation. Logistic regression analysis showed that propofol dosage, menopausal days, and State Anxiety Inventory score were independent risk factors for hypoxia. Conclusion: Patient anxiety affects the incidence of hypoxia when undergoing deep intravenous anesthesia with propofol. We can further speculate that alleviating patient anxiety can reduce the incidence of hypoxia. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR2000032167].

The Effect of Relaxation Therapy on Hypoxia During Intravenous Propofol Anesthesia in Patients With Pre-operative Anxiety: A Prospective Randomized Controlled Trial.

Background: This study aimed to investigate the effect of relaxation therapy on hypoxia during intravenous propofol anesthesia in patients with pre-operative anxiety. Methods: Two-hundred and eighty patients were randomly categorized in the experimental group (relaxation therapy group) and control group. The Spielberger State-Trait Anxiety Inventory (S-STAI) was administered 30 to 60 min pre-operatively to assess the patient's current anxiety status and select appropriate patients. Patients in the experimental group received pre-surgical relaxation therapy. Decrease in oxygen saturation during the procedure was recorded for each patient group, and the relevant data were compared between the two groups. Results: The basic S-STAI scores of the experimental and control groups were 56.88 ± 2.91 and 57.27 ± 3.56, respectively (p = 0.331). The difference was not statistically significant. The incidence of hypoxia in the experimental group during painless artificial abortion [routine blood oxygen saturation (SpO2) <95%, duration >15 s] decreased from 30 to 12.3%. Conclusion: Relaxation therapy may effectively reduce the incidence of hypoxia during painless artificial abortion by using less dose of propofol. It may help patients relieve their anxiety and improve perioperative safety. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000032109).

Integrated Bioinformatics Analysis Identifies Hub Genes Associated with Viral Infection and Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is a fatal neurodegenerative disease, the etiology of which is unclear. Previous studies have suggested that some viruses are neurotropic and associated with AD. OBJECTIVE: By using bioinformatics analysis, we investigated the potential association between viral infection and AD. METHODS: A total of 5,066 differentially expressed genes (DEGs) in the temporal cortex between AD and control samples were identified. These DEGs were then examined via weighted gene co-expression network analysis (WGCNA) and clustered into modules of genes with similar expression patterns. Of identified modules, module turquoise had the highest correlation with AD. The module turquoise was further characterized using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. RESULTS: Our results showed that the KEGG pathways of the module turquoise were mainly associated with viral infection signaling, specifically Herpes simplex virus, Human papillomavirus, and Epstein-Barr virus infections. A total of 126 genes were enriched in viral infection signaling pathways. In addition, based on values of module membership and gene significance, a total of 508 genes within the module were selected for further analysis. By intersecting these 508 genes with those 126 genes enriched in viral infection pathways, we identified 4 hub genes that were associated with both viral infection and AD: TLR2, COL1A2, NOTCH3, and ZNF132. CONCLUSION: Through bioinformatics analysis, we demonstrated a potential link between viral infection and AD. These findings may provide a platform to further our understanding of AD pathogenesis.

A Comprehensive Analysis Identified Hub Genes and Associated Drugs in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly and has become a growing global health problem causing great concern. However, the pathogenesis of AD is unclear and no specific therapeutics are available to provide the sustained remission of the disease. In this study, we used comprehensive bioinformatics to determine 158 potential genes, whose expression levels changed between the entorhinal and temporal lobe cortex samples from cognitively normal individuals and patients with AD. Then, we clustered these genes in the protein-protein interaction analysis and identified six significant genes that had more biological functions. Besides, we conducted a drug-gene interaction analysis of module genes in the drug-gene interaction database and obtained 26 existing drugs that might be applied for the prevention and treatment of AD. In addition, a predictive model was built based on the selected genes using different machine learning algorithms to identify individuals with AD. These findings may provide new insights into AD therapy.