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Su L.,Chinese People's Liberation Army | Su L.,Nankai University | Zhou R.,CAS Beijing Institute of Genomics | Liu C.,Chinese People's Liberation Army | And 8 more authors.
Journal of Trauma and Acute Care Surgery | Year: 2013

Background: Proteomics has only recently been applied to the field of critical care research. Sepsis is a major factor contributing to intensive care unit admissions and deaths. The purpose of this study was to screen potential urinary biomarkers for sepsis using A proteomics approach. Methods: Fifteen sepsis and 15 systemic inflammatory response syndrome patients were involved in this study. Urinary proteins were identified by isobaric tag for relative and absolute quantitation coupled with liquid chromatography-tandem mass spectrometry. Mass spectroscopy analysis was performed with the Mascot software and the International Protein Index. Bioinformatics analyses were performed using the hierarchy cluster analysis, the STRING software, the Gene Ontology, and the Kyoto Encyclopedia of Genes and Genome database. Results: One hundred thirty proteins were identified, and 34 differentially expressed proteins were selected (fold change, >1.5). On the basis of the Gene Ontology and the Kyoto Encyclopedia of Genes and Genome database, these 34 proteins were identified to be involved in inflammation, immunity, and structural or cytoskeletal processes. Five proteins were selected by a protein-protein interaction network for sepsis differentiation: cadherin 1, haptoglobin, complement 3, alpha-1-antitrypsin, and ceruloplasmin. Conclusion: Urinary proteomics may represent a suitable approach for sepsis-related research. The detection of urinary biomarkers is expected to become a noninvasive and acceptable method, which facilitates the close surveillance of diseases and reduces medical costs. LEVELS OF EVIDENCE: Diagnostic study, level IV. Copyright © 2013 by Lippincott Williams & Wilkins.


Su L.,Chinese PLA General Hospital | Su L.,Nankai University | Cao L.,Shenzhen Proteome Engineering Laboratory | Zhou R.,Shenzhen Proteome Engineering Laboratory | And 11 more authors.
PLoS ONE | Year: 2013

Objectives: Sepsis is the major cause of death for critically ill patients. Recent progress in proteomics permits a thorough characterization of the mechanisms associated with critical illness. The purpose of this study was to screen potential biomarkers for early prognostic assessment of patients with sepsis. Methods: For the discovery stage, 30 sepsis patients with different prognoses were selected. Urinary proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ) coupled with LC-MS/MS. Mass spec instrument analysis were performed with Mascot software and the International Protein Index (IPI); bioinformatic analyses were used by the algorithm of set and the Gene Ontology (GO) Database. For the verification stage, the study involved another 54 sepsis-hospitalized patients, with equal numbers of patients in survivor and non-survivor groups based on 28-day survival. Differentially expressed proteins were verified by Western Blot. Results: A total of 232 unique proteins were identified. Proteins that were differentially expressed were further analyzed based on the pathophysiology of sepsis and biomathematics. For sepsis prognosis, five proteins were significantly up-regulated: selenium binding protein-1, heparan sulfate proteoglycan-2, alpha-1-B glycoprotein, haptoglobin, and lipocalin; two proteins were significantly down-regulated: lysosome-associated membrane proteins-1 and dipeptidyl peptidase-4. Based on gene ontology clustering, these proteins were associated with the biological processes of lipid homeostasis, cartilage development, iron ion transport, and certain metabolic processes. Urinary LAMP-1 was down-regulated, consistent with the Western Blot validation. Conclusion: This study provides the proteomic analysis of urine to identify prognostic biomarkers of sepsis. The seven identified proteins provide insight into the mechanism of sepsis. Low urinary LAMP-1 levels may be useful for early prognostic assessment of sepsis. Trial Registration: ClinicalTrial.gov NCT01493492. © 2013 Su et al.


Su L.-X.,Chinese People's Liberation Army | Su L.-X.,Nankai University | Jiang Z.-X.,Tianjin Chest Hospital | Cao L.-C.,Shenzhen Proteome Engineering Laboratory | And 9 more authors.
Chinese Medical Journal | Year: 2013

Background Hospitalized patients often have higher rate of vitamin D deficiency than healthy people. Vitamin D levels below normal are associated with hospital stay, increased incidence of adverse prognosis and increased mortality of a number of diseases. Whether there is a relationship between vitamin D levels and infection or sepsis in the critically ill is still unclear. This study will explore the relationship between vitamin D levels and risk of infection, assessment for disease severity, and predictor of mortality. Methods To evaluate the value of vitamin D in intensive care unit (ICU) cases to sepsis, severity and prognosis assessment, high performance liquid chromatography and tandem mass spectrometry were used to measure the concentrations of vitamin D in sera of critically ill patients. The serum samples were drawn within the first 24 hours of ICU admission. Results The study included 206 people, 50 healthy controls, 51 ICU control patients and 105 ICU diagnosed with sepsis. Critically ill ICU patients (ICU sepsis and ICU control group) had lower vitamin D concentration than normal people, but septic patients showed no significant reduction of vitamin D concentration when compared with critically ill patients with no positive etiological evidence. For assessment of disease severity, there were very low negative correlations between APACHE II, SAPS II and SOFA scores and vitamin D level. Additionally, patients of different 25-(OH)D levels showed no difference whether in terms of 28-day survival (Χ2=1.78, P=0.776) or 90-day survival (Χ2=4.12, P=0.389). Multivariate Logistic regression demonstrated that APECHE II and SAPS II scores were independent risk factors to deaths caused by sepsis. Conclusion Clinically, serum concentration of vitamin D is not an indicator for diagnosis and assessment in critically ill patients (ClinicalTrial.gov identifier NCT01636232).


PubMed | Chinese PLA General Hospital and Shenzhen Proteome Engineering Laboratory
Type: Journal Article | Journal: BMJ open respiratory research | Year: 2015

To identify metabolic biomarkers that can be used to differentiate sepsis from systemic inflammatory response syndrome (SIRS), assess severity and predict outcomes.65 patients were involved in this study, including 35 patients with sepsis, 15 patients with SIRS and 15 normal patients. Small metabolites that were present in patient serum samples were measured by liquid chromatography mass spectrometry techniques and analysed using multivariate statistical methods.The metabolic profiling of normal patients and patients with SIRS or sepsis was markedly different. A significant decrease in the levels of lactitol dehydrate and S-phenyl-d-cysteine and an increase in the levels of S-(3-methylbutanoyl)-dihydrolipoamide-E and N-nonanoyl glycine were observed in patients with sepsis in comparison to patients with SIRS (p<0.05). Patients with severe sepsis and septic shock displayed lower levels of glyceryl-phosphoryl-ethanolamine, Ne, Ne dimethyllysine, phenylacetamide and d-cysteine (p<0.05) in their sera. The profiles of patients with sepsis 48h before death illustrated an obvious state of metabolic disorder, such that S-(3-methylbutanoyl)-dihydrolipoamide-E, phosphatidylglycerol (22:2 (13Z, 16Z)/0:0), glycerophosphocholine and S-succinyl glutathione were significantly decreased (p<0.05). The receiver operating characteristic curve of the differential expression of these metabolites was also performed.The body produces significant evidence of metabolic disorder during SIRS or sepsis. Seven metabolites may potentially be used to diagnose sepsis.ClinicalTrial.gov identifier NCT01649440.

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