The heart is the most vulnerable target organ in sepsis, and it has been previously reported that hydrogen sulfide (H 2 S) has a protective role in heart dysfunction caused by sepsis. Additionally, studies have demonstrated that the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway has a protective function during sepsis. However, the potential association between H 2 S and PI3K/Akt in sepsis-induced cardiac dysfunction is unclear. Therefore, the PI3K inhibitor LY294002 was used to investigate the role of PI3K/Akt signaling in the protective effects of H 2 S during sepsis-induced myocardial injury. A rat sepsis model was established using cecal ligation and puncture (CLP) surgery. Sodium hydrosulfide, a H 2 S donor, was administered intraperitoneally (8.9 µmol/kg), and serum myocardial enzyme levels, inflammatory cytokine levels, cardiac histology and cardiomyocyte apoptosis were assessed to determine the extent of myocardial damage. The results demonstrated that exogenous H 2 S reduced serum myocardial enzyme levels, decreased the levels of the inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of anti-inflammatory IL-10 following CLP. Staining of histological sections demonstrated that myocardial damage and cardiomyocyte apoptosis were alleviated by the administration of exogenous H 2 S. Western blot analysis was used to detect phosphorylated and total PI3K and Akt levels, as well as NF-κB, B-cell lymphoma-2, Bcl-2-associated X protein (Bax) and caspase levels, and the results demonstrated that H 2 S significantly increased PI3K and Akt phosphorylation. This indicated that the PI3K/Akt signaling pathway was activated by H 2 S. Additionally, H 2 S reduced Bax and caspase expression, indicating that apoptosis was inhibited, and decreased NF-κB levels, indicating that inflammation was reduced. Furthermore, the PI3K inhibitor LY294002 eliminated the protective effects of H 2 S. In conclusion, the results of the current study suggest that exogenous H 2 S activates PI3K/Akt signaling to attenuate myocardial damage in sepsis.
Sepsis-induced myocardial injury is a detrimental disorder for intensive care medicine due to its high rates of morbidity and mortality. Data suggest that nuclear factor (NF)-κB serves a critical role in the pathogenesis of myocardial injury. Hydrogen sulfide (H2S) serves an important role in the physiology and pathophysiology of regulatory mechanisms, particularly during an inflammatory reaction. However, the relationship between NF-κB and H2S in sepsis-induced myocardial injury is not well understood, and the underlying mechanisms remain unclear. In the present study, 60 male Sprague Dawley rats were randomly divided into the following six groups: A sham group, cecal ligation and puncture (CLP) group, sham + propargylglycine (PAG) group, CLP + PAG group, sham + sodium hydrosulfide (NaHS) group and CLP + NaHS group, with 10 rats in each group. The rats in all groups were sacrificed 12 h after surgery for sample collection. Compared with the sham group, it was observed that the concentrations of Creatine Kinase-MB (CK-MB) and cardiac troponin I (cTnI) in the serum, and pathological scores of myocardial tissue were significantly increased in the CLP, CLP + NaHS and CLP + PAG groups (P<0.05). The pathological scores and concentrations of CK-MB and cTnI were significantly higher in the CLP + PAG group (P<0.05) and significantly lower in the CLP + NaHS group (P<0.05) when compared with the CLP group. The expression of cystathionine-γ-lyase (CSE) mRNA and content of interleukin (IL)-10 were significantly higher in the CLP group compared with the CLP + PAG group (P<0.05), while the expression of myocardial NF-κB and content of tumor necrosis factor (TNF)-α in the CLP group were significantly lowered compared with the CLP + PAG group (P<0.05). The expression of NF-κB and content of TNF-α were significantly increased in the CLP group when compared with the CLP + NaHS group (P<0.05), while the content of myocardial IL-10 in the CLP group was significantly lower than in the CLP + NaHS group (P<0.05). In conclusion, H2S acted as an anti-inflammatory cytokine and biomarker in sepsis-induced myocardial injury. Furthermore, H2S may downregulate the NF-κB subunit p65 to mediate inflammatory responses. The present data suggest that myocardial injury in sepsis may be relieved through the regulation of H2S expression, and provide an experimental basis for the treatment of sepsis patients presenting with myocardial injury. In addition, myocardial injury in sepsis may be identified by monitoring changes in the expression of H2S.
Objective To investigate the predictive value of serum neopterin for multiple organ dysfunction syndrome (MODS) in severe burn patients. Methods Seventy-six severe burn patients with burns covering a total body surface area (TBSA) above 70% were included in this study. Of the 76 patients, 29 cases developed MODS (MODS group) and the remaining 47 subjects did not (non-MODS group). From the MODS group, 12 patients died (Death group) and 17 patients survived (Survive group). The serum level of neopterin in the MODS and non-MODS groups were examined by radioimmunoassay on following 1, 3 , 7 , 14 , 21 and 28 post-burn days (PBDs). A receiver operating characteristic (ROC) curve was used to analyse the predictive value of serum neopterin for MODS and death. Results The serum neopterin level in the MODS group was significantly higher than that of non-MODS group between 3~28 PBDs (p<0.001). However, the serum neopterin levels between the MODS and non-MODS groups following 1 PBD were not statistically significant (p>0.05). The best diagnostic performance of serum neopterin for MODS occurred 14 PBDs with the prediction sensitivity and specificity of 75.86% (56.46%~89.70%) and 85.11% (71.69%~93.80%) respectively. However, serum neopterin levels had no clinical value in predicting the death of MODS patients. The area under the ROC curve (AUC) was 0.72 (0.58~0.85), 0.81 (0.71~0.92) and 0.83 (0.72~0.94) for serum neopterin as biomarker in the prediction of MODS after 3, 7 and 14 PBDs, respectively. The AUCs were 0.50 (0.27~0.73), 0.53 (0.30~0.76) and 0.56 (0.33~0.79) for serum neopterin as biomarker in prediction of death for MODS patients after 3, 7 and 14 PBDs, respectively. Conclusion The persistent and significant increase of serum neopterin level is closely related to the development of MODS in patients with severe burns. Serum neopterin is therefore a promising serological marker for MODS early diagnosis, but has little efficacy in the prediction of the likelihood of death in severe burn patients with MODS.
The present study was performed to investigate the prognostic value of coronary computed tomography angiography (CTA) results for asymptomatic patients with coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM). A total of 164 asymptomatic patients with T2DM were enrolled at Weifang Traditional Chinese Hospital (Weifang, China). Coronary plaques and stenosis severity were evaluated after CTA. Structures >1 mm 2 adjacent to or within the coronary artery lumen that could be clearly separated from the vessel lumen, was scored as a coronary plaque. Stenosis of ≥50% was considered as being obstructive. CAD was defined as the presence of any coronary plaque or a coronary artery calcium (CAC) score of >0. A CAC score of 0 and no coronary plaques was considered to indicate the absence of CAD. A 5-year follow-up was performed to determine the impact of the CTA findings and various clinicopathological characteristics on the prognosis of all participants. The primary end-point was any cardiac event. Event-free survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. Based on the coronary CTA results, the patients were classified into 3 groups according to the extent of stenosis: Normal coronary arteries, obstructive CAD and non-obstructive CAD. Significant differences in 5-year event-free survival were identified among the groups with normal coronary arteries, non-obstructive CAD and obstructive CAD (P=0.026). Further analysis indicated that the event-free survival rate of patients with 1-vessel CAD was 94.11%, that of patients with 2-vessel CAD was 73.68% and that associated with 3-vessel CAD was 61.54%. Multivariate Cox regression analysis revealed that non-obstructive as well as obstructive CAD diagnosed by coronary CTA are prognostic indicators for asymptomatic T2DM patients [hazard ratio (HR)=11.132, 95% confidence interval (CI): 1.857-66.742, P=0.008; HR=7.792, 95% CI: 1.750-34.698, P=0.007, respectively]. In conclusion, the present study suggests that coronary CTA may predict the prognosis of asymptomatic patients with T2DM.
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