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This retrospective cohort study aimed to evaluate the association between pre-existing heart failure and both mortality and the recurrence of sepsis. A total of 16,092 sepsis patients without a history of heart failure and 841 sepsis patients with pre-existing heart failure were identified from the Medical Information Mart for Intensive Care version IV (MIMIC-IV) database. All patients were adults admitted to intensive care units, and no specific interventions were applied. After matching, Kaplan–Meier survival analysis showed significantly poorer long-term survival rates in patients with heart failure, both in the original (p < 0.0001) and the matched cohort (p = 0.00059). Mortality rates were tracked over different time periods, revealing that the mortality disparity became evident after the first year (p = 0.029). Besides, the cumulative incidence of sepsis recurrence was substantially higher in patients with a history of heart failure (p < 0.001) when deaths without recurrence were treated as competing events. Moreover, there was no statistically significant difference observed in the deaths without recurrence between the two groups (p = 0.251). In conclusion, pre-existing heart failure is associated with an increased risk of long-term mortality, which may be partly explained by a higher incidence of recurrent sepsis in this population. [ABSTRACT FROM AUTHOR]

Field experiments were conducted to study the effects of nitrogen application rates and straw returning on grain yield, nutrient accumulation, nutrient release from straw and nutrient balance in late sowing wheat. The results showed that straw returning together with appropriate application of nitrogen fertilizer improved the grain yield. Dry matter, nitrogen, phosphorus and potassium accumulation increased significantly as the nitrogen application rate increased. At the same nitrogen application rate (270 kg N·hm–2), the dry matter, phosphorus and potassium accumulation of the treatment with straw returning were higher than that without straw returning, but the nitrogen accumulation was lower. Higher-rate nitrogen application promoted straw decomposition and nutrient release, and decreased the proportion of the nutrient released from straw after jointing. The dry matter, phosphorus and potassium release from straw showed a reverse 'N' type change with the wheat growing, while nitrogen release showed a 'V' type change. The nutrient surplus increased significantly with the nitrogen application rate. At the nitrogen application rate for the highest grain yield, nitrogen and potassium were surplus significantly, and phosphorus input could keep balance. It could be concluded that as to late sowing wheat with straw returning, applying nitrogen at 257 kg·hm–2 and reducing potassium fertilizer application could improve grain yield and reduce nutrients loss. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCF Fbxw7α from Fn14, dismantles Lys 48 -linked polyubiquitination of Fn14 and stabilizes it. Pharmacological deactivation of Fn14 with monoclonal antibody ITEM-2 provides effective protection against lethal sepsis and AKI in mice. Our study underscores an adaptive mechanism whereby TLR4 regulates SCF Fbxw7α -dependent Fn14 stabilization during inflammatory tubular damage and further supports investigation of targeting Fn14 in clinical trials of patients with septic AKI.

Background: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis., Methods: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs., Results: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470)., Conclusions: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force., Trial Registration: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

Field experiments were conducted to study the effects of nitrogen application rates and straw returning on grain yield, nutrient accumulation, nutrient release from straw and nutrient balance in late sowing wheat. The results showed that straw returning together with appropriate application of nitrogen fertilizer improved the grain yield. Dry matter, nitrogen, phosphorus and potassium accumulation increased significantly as the nitrogen application rate increased. At the same nitrogen application rate (270 kg N · hm(-2)), the dry matter, phosphorus and potassium accumulation of the treatment with straw returning were higher than that without straw returning, but the nitrogen accumulation was lower. Higher-rate nitrogen application promoted straw decomposition and nutrient release, and decreased the proportion of the nutrient released from straw after jointing. The dry matter, phosphorus and potassium release from straw showed a reverse 'N' type change with the wheat growing, while nitrogen release showed a 'V' type change. The nutrient surplus increased significantly with the nitrogen application rate. At the nitrogen application rate for the highest grain yield, nitrogen and potassium were surplus significantly, and phosphorus input could keep balance. It could be concluded that as to late sowing wheat with straw returning, applying nitrogen at 257 kg · hm(-2) and reducing potassium fertilizer application could improve grain yield and reduce nutrients loss.

Tanshinone IIA is a lipophilic abietane diterpene compound, which exhibits protective effects against ischaemia/reperfusion injury; however, the pathways responsible for the myocardial protective activities of tanshinone IIA remain to be elucidated. The aim of the present study was to investigate the effect of tanshinone IIA on the Janus‑activated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, which is associated with cardiac dysfunction during ischemia/reperfusion. The results demonstrated that tanshinone IIA protected myocardial cells from hypoxia/ischemia‑induced injury in vitro and recovered decreased cell viability due to activation of the JAK2/STAT3 pathway, with 10 µM tanshinone IIA exhibiting the most potent protective effects. Flow cytometric analysis revealed that tanshinone IIA reversed the apoptotic aggravation induced by JAK2/STAT3 inhibitors following hypoxic ischemia. However, JAK2 inhibitors promoted the myocardial protective effect of tanshinone IIA from hypoxic‑ischemic injury. Furthermore, tanshinone IIA and JAK2/STAT3 inhibitors in combination augmented the protection of myocardial cells from apoptosis induced by ischemia/reperfusion preconditioning in vivo. In conclusion, the results of the present study indicated that JAK2/STAT3 inhibitors may enhance the protective effect of tanshinone IIA on cardiac myocytes from hypoxic ischemia-induced injury, therefore suggesting that JAK2/STAT3 inhibitors may have a potential application in combination therapies with tanshinone IIA.

Objective: To investigate the cAMP response element binding protein (CREB) expression and activity in acute lung injury induced by endotoxinemia following hemorrhagic shock., Methods: Thirty-six rabbits were randomly divided into 3 equal groups: 2 hours after the endotoxinemia following hemorrhagic shock group that underwent exsanguination, injected intraperitoneally with lipopolysaccharide (LPS) after the blood pressure became stable, and then underwent extraction of carotid blood for blood gas test and killed 2 hours later; 12 hours after the endotoxinemia following hemorrhagic shock (two hits) group: undergoing the above mentioned management and being killed 12 hours later; and control group, undergoing sham operation. The lungs were taken out to undergo histological examination. The partial arterial blood pressure of oxygen (PaO2) and wet lung weight to dry lung weight ratio (W/D) were measured. The concentration of tumor necrosis factor (TNF)-alpha in the lung homogenate was measured by enzyme-linked immunosorbent assay (ELISA). The expression of CREB in the lung was assessed by Western blotting and the CREB/DNA binding activity was assayed with electrophoretic mobility shift assay (EMSA)., Results: Pathological examination of the lung tissues showed that the alveolar structures were severely destroyed and large number of WBC infiltrating in both alveolar sacs and pulmonary interstitial with RBC leakage the 12 hours after the endotoxinemia following hemorrhagic shock group, and the changes were mild in the 2 hours after two hits group. The PaO2 was significantly reduced in the 12 hour after endotoxinemia following hemorrhagic shock group compared with the control group (P < 0.01). The lung W/D and the concentration of TNF-alpha in lung homogenate were significantly increased in the 12 hours after endotoxinemia following hemorrhagic shock group compared with the control group (both P < 0.01). Nevertheless there were not significant differences in the PaO2, W/D and TNF-alpha between the 2 hours after two hits group and the control group. The expression level and DNA binding activity of CREB in the lung were significantly higher in both 2 and 12 hours after endotoxinemia following hemorrhagic shock groups than those in the control group (all P < 0.01)., Conclusion: CREB in the lung is activated by endotoxinemia following hemorrhagic shock and may participate in the inflammatory response in acute lung injury by regulating the expression of inflammatory factors.