Objective To evaluate the effects of intensive care unit (ICU)-acquired hypernatremia (IAH) on the outcome of septic shock patients. Methods This retrospective study analyzed 116 septic shock patients admitted to the ICU of the First Affiliated Hospital of Soochow University from August 2018 to December 2022. Patients were divided into two groups: IAH group and normonatremia group. χ2 test, t test and the Mann-Whitney U test of the non-parametric test were used to compare the differences in clinical data between the two groups. Independent risk factors for IAH were identified by unconditioned Logistic regression analysis, and receiver operating characteristic (ROC) curves were constructed to determine their role in predicting IAH. The Kaplan-Meier curve was used to evaluate the effects of IAH and its duration on 28-day survival. Results Renal insufficiency, K+ concentration, body temperature max, mechanical ventilation, chronic critical illness, rapid recovery, sepsis-associated encephalopathy, persistent inflammation, immunosuppression and catabolism syndrome, and the length of stay in ICU had significant differences (P<0.05). Multivariate logistic regression analysis showed: total urine volume in the previous 3 days [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.01 - 1.16, P=0.019] and sodium content in enteral nutrition preparations (670 mg) (OR 6.00, 95%CI 1.61 - 22.42, P=0.006) were independent risk factors for IAH. In addition, the area under the ROC curve of total urine output in the first 3 days was 0.800 (95%CI 0.678 - 0.922, P=0.001). Finally, the duration of IAH was significantly correlated with 28-day survival rate (P=0.020). Conclusions IAH is a common and serious complication in septic shock, and is the main cause of poor prognosis. Sodium status may act as an ideal screening tool for patients with septic shock.
ObjectiveTo observe the influence of heat shock protein 27 (HSP27) sensibilization to retinal ganglion cells (RGC) apoptosis of rats. MethodsThirty-five female Wistar rats were randomly divided into HSP27 sensibilization group (15 rats), borate buffer solution (BBS) control group (15 rats) and normal group (5 rats). The rats in HSP27 sensibilization group were received hypodermic injection in rear limb with 100 μg HSP27 and complete freund adjuvant, intraperitoneal injection with 1 μg pertussis toxin. The BBS control group received the same volume of BBS at the same site. The normal group received no intervention. The intraocular pressure was measured 3 days before injection and 1, 2, 4, 6, 8 weeks after injection. Four, 6 and 8 weeks after injection, the retinal frozen sections was made to observe RGC apoptosis by terminal-deoxynucleoitidyl transferase mediated nick end labeling. The anti-HSP27 level in serum and cerebrospinal fluid were detected by enzyme linked immunosorbent assay. ResultsThere was no obvious change of intraocular pressure in rats in 3 groups before injection (P>0.05). RGC apoptosis was observed in HSP27 sensibilization group 4 weeks after injection, and increased significantly at 6 weeks after injection. There was no RGC apoptosis in BBS control group and normal group. The level of anti-HSP27 in serum and cerebrospinal fluid of HSP27 sensibilization group occurred at 4 and 6 weeks after injection respectively, decreased with prolongation of injection time. Compared with BBS control group and normal group, the RGC apoptosis rate, anti-HSP27 level in serum and cerebrospinal fluid of HSP27 sensibilization group were significantly increased (P<0.05). There was no significant difference of the RGC apoptosis rate, anti-HSP27 level in serum and cerebrospinal fluid between BBS control group and normal group (P>0.05). ConclusionsHSP27 sensibilization could promote the RGC apoptosis. The variation trend of anti-HSP27 level in cerebrospinal fluid is consistent with the RGC apoptosis.
Objective To study the effects of heat shock proteins (HSPs) in the course of hepatic ischemia reperfusion injury (HIRI), and analyze its mechanism. Methods The relationship between HSPs and HIRI was studied by reviewing literatures. Results HSPs was a kind of stress protein induced after cell was sitmulated by the stress. It could improve body′s tolerance to tough situation. Though hepatic ischemia reperfusion usually results in serious hepatic injury, at the same time it could induce can increase the production of HSPs that can protect liver from and lessen ischemia reperfusion injury. Conclusion HSPs can improve the tolerance to HIRI and lessen injury. In addition, HSPs is thought to be markers of HIRI, and can be used as a efficient indicator to test the level of hepatic injury and assess prognosis.
ObjectiveTo investigate the influence of heat shock protein A2 (HSPA2) on the biological behavior of pancreatic adenocarcinoma cells and its mechanism. MethodsThe expressions of HSPA2 were determined in the human pancreatic adenocarcinoma cell lines (PANC-1, BxPC-3, and AsPC-1) using the Western blot. Subsequently, the cells with the lowest and highest HSPA2 expressions among these three lines were selected for conducting overexpression and knockdown experiments targeting HSPA2, respectively. The cellular proliferation, cell clonogenesis, migration, and invasion capabilities were assessed using MTT, clonogenic assay, and Transwell assay, respectively. Additionally, the impact of HSPA2 on the expression of key markers of epithelial-mesenchymal transition (EMT) was examined using the Western blot. The potential target molecules of HSPA2 were identified through immunoprecipitation assay and mass spectrometry. The rescue experiments further explored the regulatory relation between the HSPA2 and its target molecules. The influence of HSPA2 on pancreatic adenocarcinoma growth was investigated through establishment of xenograft tumor model in nude mice. ResultsThe HSPA2 exhibited the lowest expression in the PANC-1 cells and the highest expression in the AsPC-1 cells among the three cell lines. Subsequent functional studies demonstrated that the overexpression of HSPA2 in the PANC-1 cells markedly promoted proliferation, cell clonogenesis, migration, and invasion, while the knockdown of HSPA2 expression in the AsPC-1 cells markedly inhibited these processes. The Western blot analysis further showed that the HSPA2 overexpression downregulated E-cadherin expression and upregulated N-cadherin and Vimentin expressiones, whereas the HSPA2 knockdown produced opposite effects. The rescue experiments indicated that the HSPA2 promoted the EMT in pancreatic adenocarcinoma cells by upregulating Yes associated protein (YAP). The subcutaneous xenograft tumor experiments in the nude mice showed that the HSPA2 knockdown inhibited tumor growth. ConclusionThe results of this study suggest that HSPA2 promotes EMT via upregulating YAP, which facilitates proliferation, migration, and invasion of pancreatic adenocarcinoma cells.
Objective To identify potential hub genes and key pathways in the early period of septic shock via bioinformatics analysis. MethodsThe gene expression profile GSE110487 dataset was downloaded from the Gene Expression Omnibus database. Differentially expressed genes were identified by using DESeq2 package of R project. Then Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were constructed to investigated pathways and biological processes using clusterProfiler package. Subsequently, protein-protein interaction (PPI) network was mapped using ggnetwork package and the molecular complex detection (MCODE) analysis was implemented to further investigate the interactions of differentially expressed genes using Cytoscape software. Results A total of 468 differentially expressed genes were identified in septic shock patients with different responses who accepted early supportive hemodynamic therapy, including 255 upregulated genes and 213 downregulated genes. The results of GO and the KEGG pathway enrichment analysis indicated that these up-regulated genes were highly associated with the immune-related biological processes, and the down-regulated genes are involved in biological processes related to organonitrogen compound, multicellular organismal process, ion transport. Finally, a total of 23 hub genes were identified based on PPI and the subcluster analysis through MCODE software plugin in Cytoscape, which included 19 upregulated hub genes, such as CD28, CD3D, CD8B, CD8A, CD160, CXCR6, CCR3, CCR8, CCR9, TLR3, EOMES, GZMB, PTGDR2, CXCL8, GZMA, FASLG, GPR18, PRF1, IDO1, and additional 4 downregulated hub genes, such as CNR1, GPER1, TMIGD3, GRM2. KEGG pathway enrichment analysis and GO functional annotation showed that differentially expressed genes were primarily associated with the items related to cytokine-cytokine receptor interaction, natural killer cell mediated cytotoxicity, hematopoietic cell lineage, T cell receptor signaling pathway, phospholipase D signaling pathway, cell adhesion molecules, viral protein interaction with cytokine and cytokine receptor, primary immunodeficiency, graft-versus-host disease, type 1 diabetes mellitus. Conclusions Some lymphocytes such as T cells and natural killer cells, cytokines and chemokines participate in the immune process, which plays an important role in the early treatment of septic shock, and CD160, CNR1, GPER1, and GRM2 may be considered as new biomarkers.
Objective To investigate the predictive value of extracorporeal membrane oxygenation (ECMO) pre-computer multiple scoring systems in the mortality of patients with cardiogenic shock. Methods A retrospective analysis was performed on 100 patients with cardiogenic shock due to various reasons who were treated with veno-arterial ECMO (VA-ECMO) from July 2020 to July 2022. The patients were followed up for 30 days and divided into a survival group (35 cases) and a death group (65 cases) according to whether they survived 30 days after withdrawal. General clinical data, blood biochemistry data within 24 hours before ECMO, ventilator parameters, past medical history and other data were collected, and sequential organ failure score (SOFA) before VA-ECMO, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), survival after veno-arterial ECMO (SAVE) score and modified SAVE score were calculated. Blood biochemical indicators and clinical scores related to patient prognosis were screened using two-independent sample t test or Man-Whitney U test. The predictive efficacy of each score on short-term prognosis (30-day post-discharge mortality) was evaluated by receiver operating characteristic curve and area under curve (AUC). Results There were significant differences in APACHEⅡ score, SAVE score and modified SAVE score between two groups (P<0.05). The AUC and its 95%CI of APACHEⅡ score was 0.696 (95%CI 0.592 - 0.801), of SAVE score was 0.617 (95%CI 0.498 - 0.736), and of post SAVE score was 0.664 (95%CI 0.545 - 0.782), respectively. All AUCs were relatively low (<0.75). Conclusion SOFA, APACHEⅡ, SAVE score and modified SAVE score have limited clinical value in the prognosis assessment of ECMO patients, and do not show obvious advantages.