Background Sepsis is a highly heterogeneous syndrome with stratified severity levels and immune states. Even in patients with similar clinical appearances, the underlying signal transduction pathways are significantly different. To identify the heterogeneities of sepsis from multiple angles, we aimed to establish a combined risk model including the molecular risk score for rapid mortality prediction, pathway risk score for the identification of biological pathway variations, and immunity risk score for guidance with immune-modulation therapy. Methods We systematically searched and screened the mRNA expression profiles of patients with sepsis in the Gene Expression Omnibus public database. The screened datasets were divided into a training cohort and a validation cohort. In the training cohort, authentic prognostic predictor characteristics (differentially expressed mRNAs, pathway activity variations and immune cells) were screened for model construction through bioinformatics analysis and univariate Cox regression, and a P value less than 0.05 of univariate Cox regression on 28-day mortality was set as the cut-off value. The combined risk model was finally established by the decision tree algorithm. In the validation cohort, the model performance was assessed and validated by C statistics and the area under the receiver operating characteristic curve (AUC). Additionally, the current models were further compared in clinical value with traditional indicators, including procalcitonin (PCT) and interleukin-8 (IL-8). Results Datasets from two sepsis cohort studies with a total of 585 consecutive sepsis patients admitted to two intensive care units were downloaded as the training cohort (n = 479) and external validation cohort (n = 106). In the training cohort, 15 molecules, 20 pathways and 4 immune cells were eventually enrolled in model construction. These prognostic factors mainly reflected hypoxia, cellular injury, metabolic disorders and immune dysregulation in sepsis patients. In the validation cohort, the AUCs of the molecular model, pathway model, immune model, and combined model were 0.81, 0.82, 0.62 and 0.873, respectively. The AUCs of the traditional biomarkers (PCT and IL-8) were 0.565 and 0.585, respectively. The survival analysis indicated that patients in the high-risk group identified by models in the current study had a poor prognosis (P < 0.05). The above results indicated that the models in this study are all superior to the traditional biomarkers for the predicting the prognosis of sepsis patients. Furthermore, the current study provides some therapeutic recommendations for patients with high risk scores identified by the three submodels. Conclusions In summary, the present study provides opportunities for bedside tests that could quantitatively and rapidly measure heterogeneous prognosis, underlying biological pathway variations and immune dysfunction in sepsis patients. Further therapeutic recommendations for patients with high risk scores could improve the therapeutic system for sepsis.
Background: Cervical vertigo commonly concurs in patients with neck pain, but the concurrent mechanism of these 2 symptoms still remains unclear. We previously reported a bidirectional segmental nerve fiber connection between cervical spinal and sympathetic ganglia, which provided a hypothesis that this connection between the 2 ganglia may be the anatomic basis for the concurrence of neck pain and cervical vertigo. However, this concurrent mechanism needs biochemical and functional evidence. Objectives: This study aimed to investigate a possible noradrenergic pathway between cervical spinal and sympathetic ganglia. Study Design: We performed both clinical and laboratory research. Clinical observation was a prospective case–control study. Setting: Clinical study took place in our hospital; laboratory study was in an orthopedic laboratory. Methods: Cervical lamina block therapy used in patients with cervical vertigo was clinically evaluated; norepinephrine (NE) expressions in cervical sympathetic ganglia were analyzed using immunohistochemical staining after electrical stimulation to the cervical spinal ganglia; the influence of phentolamine local injection to the vertebrobasilar artery flow was experimentally measured. Results: Cervical lamina block therapy could significantly shorten the clinical hospital stays of patients with cervical vertigo (P = 0.000) and improve vertebral artery flow (P < 0.05). NE expressions in superior cervical sympathetic ganglia (SCG) or inferior cervical sympathetic ganglia (ICG) increased significantly when ipsilateral C2 to C3 or C6 to C8 spinal ganglia were electrically stimulated, respectively. Adrenergic receptor block with phentolamine significantly inhibited the decrease of basilar artery (BA) flow induced by electrical stimulation of the cervical spinal ganglia. The change range of BA flow caused by stimulations of C2 to C3 and C6 to C8 spinal ganglia was more than that of C4 and C5. Limitations: The inpatients observed in this clinical study might be influenced by some factors including emotion, diet, sleep, and others. The limitations of the laboratory study included animal species and small sample size. Conclusions: Adrenergic system could play a part in cervical spinal ganglia altering the vertebrobasilar artery system. It could provide a neurochemical foundation between neck pain and vertigo, and that segmental functional connections exist between cervical spinal and sympathetic ganglia.
The role of CD8 + T cells in asthma has not been fully discussed. The mechanisms of CD4 + and CD8 + cells in severe asthma (SA) development were compared. The microarray data (GSE31773) was down loaded from the Gene Expression Omnibus (GEO) database, including 20 samples of CD4 + and CD8 + T cells, which were collected from 8 health controls (HC), 4 non severe asthma (NSA) and 8 SA patients. DEGs of CD4 + and CD8+ T cells in the HC vs. NSA and HC vs. SA groups were identified using the limma package in R. GO and pathway enrichment analysis of the common DEGs between the two groups were ana lyzed using DAVID. The interactive network of DEGs and significant modules were further explored. In CD4 + cells, there were 168 DEGs in HC vs. NSA group and 685 DEGs in HC vs. SA group, while for CD8 + T cells there were 719 DEGs in the HC vs. NSA groups and 1255 DEGs in the HC vs. SA groups. Besides, 80 common DEGs from CD4 + samples were enriched in the MAPKKK cascade and molecular metabolism, and 385 common DEGs of CD8 + T cells were significantly related with cell apoptosis and transformation. Moreover, two significant modules of DEGs in CD4 + were found to be involved with MPO and BPI. One module of CD8 + T cells containing PDHA1 and MRPL42 was identified to be related with glycolysis. In con clusion, MPO and BPI in CD4 + , and PDHA1 and MRPL42 in CD8 + T cells might be used as specific biom arkers of SA progression. Therapy targeting the functions of CD4 + and CD8 + T cells may provide a novel per spective for SA treatment.
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