| Objective: Lable-free proteomics and bioinformatics analysis techniques were used to screen differential proteins related to the occurrence of mental cognitive dysfunction in viral encephalitis,and differentially expressed proteins(DEPs)were used as bearing points to search for perioperative neurocognitive dysfunction(PND)biological targets,which provide new research strategies and data bases.Methods:(1)From December 2020 to February 2021,the cerebrospinal fluid(CSF)within 24 hours after admission was selected from 5 patients in the viral encephalitis with mental cognitive disorders(EM group),6 patients in the viral encephalitis without mental cognitive disorders group(NED group)and 5 patients in the non-encephalitis(N group)in the affiliated hospital of Zunyi Medical University as the preliminary experiment.Label-free proteomics technology was used to conduct quality inspection,enzymatic hydrolysis,mass spectrometry detection and data analysis of proteins in CSF,enrich DEPs by GO and KEGG pathways,and analyze and screen DEPs in mental and cognitive functions.(2)CSF samples of 20 cases in EM,20 cases in NED and 20 cases in N group collected in the same period were collected.ELISA method was used to detect the expression changes of DPEs related to mental and cognitive dysfunction for sample size calculation,and the e xpanding the sample size to require 50 tests per group.(3)Basic information such as the patient’s age,gender,hospital stay,and routine CSF biochemistry at the time of admission were collected.(4)The patients were scored with the mini-mental state examination scale(MMSE),and the correlation between the expression of mental and cognitive function DEPs in CSF and the MMSE score was analyzed.Results:1.Proteomic detection of DEPs,(1)EM and N groups: a total of 1274 were identified,(2)NED and N groups: a total of 1223 were identified,(3)EM and NED groups: a total of 1337 were identified.(1)GO analysis in biological process(BP),cellular composition(CC),molecular function(MF)process: DEPs are mainly concentrated in biological synapses,neural development,angiogenesis,etc.(2)KEGG analysis found that DEPs were mainly enriched in the pathways of propionate metabolism,galactose metabolism,and cytokine-cytokine receptor interaction.(3)Through GO and KEGG enrichment,the protein genes that may be mental cognition disorders are finally screened out,which are: vascular cell adhesion molecule 1(VCAM1),insulin-like growth factor binding protein 4(IGFBP4),colony stimulating factor 1 receptor(CSF1R),cytokine-like protein(CYTL1),triggering receptor expressed on myeloid cells 2(TREM2)granulocyte macrophage colony stimulating factor 2 receptor α(CSF2RA),beta-1,3-glucuronyltransferase 3(B3GAT3),plexin domain-containing protein 2(PLXDC2),neuroligin-1(NLGN1),C-type natriuretic peptide(NPPC).(4)The number of articles and research fields of the above 10 targets were searched through the Pub Med website,and it was finally speculated that CSF1 R,TREM2,and VCAM1 may be the targets of viral encephalitis with mental and cognitive dysfunction.2.(1)Calculation of sample size: Detect CSF1 R,TREM2,VCAM1 proteins in 20 CSF samples in each of the three groups and calculate the sample size required for the experiment.The calculation result is 50 cases in each group,a total of 150 cases.(2)The protein expression levels of CSF1 R,TREM2 and VCAM1 in CSF of the three groups: the protein expression level of CSF1 R in the EM group was higher than that in the NED group(p < 0.001),the expression levels of TREM2 and VCAM1 proteins in the EM group were higher than those in the NED group,and the NED group was higher In group N,there was statistical significance among the three groups(p < 0.001).3.Basic information of the three groups of patients:(1)There was no significant difference in age and gender between groups(p(29)0.05).(2)The number of days in hospital,the hospitalization days of EM group and NED group were longer than those of N group,and the difference was statistically significant(p < 0.05).(3)CSF routine biochemistry: EM and N groups had lower CSF Leuk than NED group,and the difference was statistically significant(p < 0.05).There was no significant difference in CSF Cl between groups(p < 0.05).The CSF Glu in the EM group was higher than that in the NED group,and the difference was statistically significant(p <0.05).The CSF Pro of the EM and NED groups was higher than that of the N group,and the difference was statistically significant(p < 0.05).4.(1)MMSE score: the score of EM group was lower than that of NED and N groups,and the difference was statistically significant(p < 0.05).2)Correlation analysis: TREM2 and VCAM1 were negatively correlated with MMSE.The correlation coefficient between TREM2 and MMSE was-0.226(p < 0.05).The correlation coefficient between VCAM1 and MMSE was-0.245(p < 0.05).Conclusion: The differential proteins related to mental cognitive dysfunction in viral encephalitis are CSF1 R,TREM2 and VCAM1.Combined with mini-mental state examination scale,the bearing points TREM2 and VCAM1 may be the biological targets of PND.Objective: Combined network pharmacology and bioinformatics analysis to explore the expression and regulation of biological targets in perioperative neurological dysfunction(PND)and viral encephalitis with mental cognitive disorder,and find their common targets and pathways.The underlying mechanism of PND is then explored.Methods: PND-related genes were searched in Online Mendelian Inheritance in Man(OMIM)database,Gene Cards database,Des Ge NET database and Therapeutic Target Database(TTD)database,respectively.The retrieved genes were intersected with the biological targets of viral encephalitis with mental cognitive disorder,and the obtained intersected target proteins were amplified on the STRING website.The protein interaction network(PPI)was constructed with the help of the STRING platform,and the key targets were visualized and screened with Cytoscape 3.7.1 software.The Cytoscape platform was used to perform GO biological process(BP),cellular component(CC),molecular function(MF)enrichment for key target genes and analyze the KEGG signaling pathway enrichment of key targets.Results: A total of 2575 PND targets were retrieved from 4 databases,and 7 targets intersected with viral encephalitis with mental cognitive disorder,they were VCAM1,NPPC,NLGN1,IGFBP4,CSF2 RA,TREM2 and CSF1 R.The analysis showed that the key targets mainly involve 2189 items such as cell response to peptide,peptide tyrosine phosphorylation,insulin-like growth factor I binding,integrin binding,complex,synaptic membrane,etc.They were mainly enriched in 161 significantly related pathways such as PI3K-Akt signaling pathway,Rap1 signaling pathway,Ras signaling pathway,and MAPK signaling pathway.PI3K-Akt signaling pathway was the most important one.Conclusion: Target enrichment analysis of viral encephalitis with mental cognitive disorder revealed that VCAM1,TREM2,CSF1 R and NLGN1 are disease targets of PND,and PI3K-Akt signaling pathway may be a mechanism pathway of PND. |
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