OBJECTIVE: To assess the prognostic value of Charlson weighted index of comorbidities (WIC) combined with sequential organ failure assessment (SOFA) score and procalcitonin (PCT) in sepsis patients in intensive care unit (ICU). METHODS: A prospective cohort study was conducted. 118 patients with sepsis admitted to ICU of Sichuan Provincial People's Hospital from July 2015 to June 2018 were enrolled. The clinical data of the patients including gender, age, pathogenic factors, site of infection, underlying diseases and 28-day prognosis were collected, while the WIC score at ICU admission, the acute physiology and chronic health evaluation II (APACHE II) score and SOFA score within 24 hours after ICU admission, serum PCT level within 1 hour after ICU admission were recorded. The patients were divided into survival group and death group according to 28-day prognosis, and the clinical data of patients with different prognosis were compared. Multivariate Logistic regression model was used to analyze the relationship between WIC score, SOFA score, PCT level and the outcomes of patients. The receiver operating characteristic (ROC) curve was drawn to evaluate the value of WIC score, SOFA score, and PCT level for predicting the prognosis of patients with sepsis. RESULTS: In this study, 118 eligible sepsis patients were enrolled, and 94 patients survived at 28 days, and 24 patients died with a 28-day mortality of 20.3%. Compared with the survival group, the patients in the death group were older and had higher APACHE II score, WIC score, SOFA score, and serum PCT levels. Pathogenic factors analysis showed that the proportion of pulmonary infection in the death group was the highest (62.5%), while in the survival group the main cause was multiple injury (36.2%), followed by pulmonary infection (30.9%). Basic diseases analysis showed that the proportions of tumor, type 2 diabetes, chronic lung disease, cerebrovascular disease, chronic kidney disease, chronic liver disease, and chronic cardiac insufficiency in the death group were significantly higher than those in the survival group. The age [odds ratio (OR) = 1.279, 95% confidence interval (95%CI) was 1.065-1.536], APACHE II score (OR = 1.255, 95%CI was 1.083-1.455), WIC score (OR = 1.429, 95%CI was 1.304-1.568), SOFA score (OR = 1.331, 95%CI was 1.456-1.545), and serum PCT level (OR = 1.497, 95%CI was 1.146-1.547) were related to the 28-day prognosis of patients with sepsis, and were independent predictors of 28-day prognosis in patients with sepsis (all P < 0.01). ROC curve analysis showed that the area under ROC curve (AUC) of WIC score, SOFA score, serum PCT level and combined prediction probability was 0.712 (95%CI was 0.588-0.836), 0.801 (95%CI was 0.695-0.908), 0.889 (95%CI was 0.798-0.979), 0.943 (95%CI was 0.884-1.000), respectively, indicating that the accuracy of combined parameters to predict survival outcome was higher than that of any single parameter with the sensitivity of 91.7% and the specificity of 83.0%. CONCLUSIONS WIC score, SOFA score combined with serum PCT level can improve the accuracy of predicting the 28-day prognosis in patients with sepsis.
Humans ; Intensive Care Units ; Organ Dysfunction Scores ; Procalcitonin/metabolism* ; Prognosis ; Prospective Studies ; ROC Curve ; Retrospective Studies ; Sepsis/metabolism*

OBJECTIVES: To study the effect of procalcitonin (PCT) on lipopolysaccharide (LPS)-induced expression of the pyroptosis-related proteins nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and caspase-1 in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were induced by LPS to establish a model of sepsis-induced inflammatory endothelial cell injury. The experiment was divided into two parts. In the first part, HUVECs were randomly divided into four groups: normal control, LPS (1 μg/mL), PCT (10 ng/mL), and LPS+PCT (n=3 each). In the second part, HUVECs were randomly grouped: normal control, LPS, and LPS+PCT of different concentrations (0.1, 1, 10, and 100 ng/mL) (n=3 each). Quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NLRP3 and caspase-1 in each group. RESULTS: In the first experiment: compared with the normal control group, the PCT, LPS, and LPS+PCT groups had significantly upregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05); compared with the LPS group, the LPS+PCT group had significantly downregulated mRNA and protein expression levels of NLRP3 and caspase-1 (P<0.05). In the second experiment: compared with those in the LPS group, the mRNA and protein expression levels of NLRP3 and caspase-1 in the LPS+PCT of different concentrations groups were significantly downregulated in a concentration-dependent manner (P<0.05). CONCLUSIONS LPS can promote the expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs, while PCT can inhibit the LPS-induced expression of the pyroptosis-related proteins NLRP3 and caspase-1 in HUVECs in a concentration-dependent manner.
Humans ; Caspase 1/metabolism* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Lipopolysaccharides/pharmacology* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Procalcitonin ; Nucleotides/pharmacology*

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.
Animals ; Anti-Inflammatory Agents/therapeutic use* ; C-Reactive Protein ; Caspase 3/metabolism* ; Interleukin-10 ; Interleukin-6/metabolism* ; Lactate Dehydrogenases/metabolism* ; Myeloblastin/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; NF-kappa B/metabolism* ; Network Pharmacology ; Procalcitonin/therapeutic use* ; Sepsis/genetics* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; bcl-2-Associated X Protein/metabolism*

OBJECTIVETo study the expression of serum cytokines, interleukin-38 (IL-38) and interleukin-1β (IL-1β) in the acute phase of Kawasaki disease (KD) in children and the association of IL-38 and IL-1β with inflammatory response in the acute phase and the development of coronary artery lesion (CAL).

METHODSA total of 40 children with KD who were hospitalized in the hospital between July 2015 and June 2016 were enrolled, with 21 children in the CAL group and 19 in the non-CAL (NCAL) group. Thirty healthy children and 19 children with infection and pyrexia, who were matched for sex and age, were enrolled as healthy control group and pyrexia control group respectively. ELISA was used to measure the serum levels of IL-38 and IL-1β in the 40 children in the acute phase of KD. Spearman's rank correlation analysis was used to investigate the correlations of IL-1β and IL-38 with interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), triglyceride (TG), and total cholesterol (TC).

RESULTSThe serum level of IL-38 in the children in the acute phase of KD was significantly lower than that in the healthy control group (P<0.05), but significantly higher than that in the pyrexia control group (P<0.05). There was no significant difference in the level of IL-38 between the CAL and NCAL groups (P>0.05). The children in the acute phase of KD had a significantly higher level of IL-1β than the healthy control group (P<0.05), while there was no significant difference between this group and the pyrexia control group (P>0.05). There was also no significant difference in the level of IL-1β between the CAL and NCAL groups (P>0.05). Serum IL-1β and IL-38 levels were not correlated with serum levels of CRP, ESR, PCT, IL-6, and NT-ProBNP or blood lipids (TG and TC) (P>0.05).

CONCLUSIONSIL-38 is involved in an inflammatory response in the acute phase of KD and may exert an anti-inflammatory effect, which is opposite to the effect of IL-1β to promote inflammatory response. However, there is no significant correlation between these two cytokines and the development of CAL in KD.

Acute Disease ; Atrial Natriuretic Factor ; blood ; Blood Sedimentation ; C-Reactive Protein ; metabolism ; Case-Control Studies ; Child ; Child, Preschool ; Cholesterol ; blood ; Coronary Artery Disease ; blood ; etiology ; pathology ; Coronary Vessels ; pathology ; Female ; Humans ; Infant ; Interleukin-1beta ; blood ; Interleukins ; blood ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; complications ; Procalcitonin ; blood ; Protein Precursors ; blood ; Triglycerides ; blood