The efficacy of stem cells for the treatment of renal failure is widely recognized; however, an excessive volume of stem cells can block the capillaries; thus, the potential risks should not be ignored. Stem cell exosomes are secretory extracellular vesicles with a size of 30–150 nm, which have similar functions to stem cells but are much smaller in size. This study aims to investigate the role of human umbilical cord mesenchymal stem cells (UCMSCs)-derived exosomes in the treatment of renal failure caused by ischemia-reperfusion. Fifty 8-week-old female C57 mice underwent bilateral renal ischemia-reperfusion surgery for 30 minutes. After 4 weeks, the treated group received UCMSCs-derived exosomes treatment, and the control group was solely injected with the same amount of PBS. At the age of 16 weeks, the kidney function, kidney damage, inflammatory responses and oxidative stress were measured. Moreover, the effect of UCMSCs-derived exosomes on the phenotype of M1 macrophages was also tested. The results showed that UCMSCsderived exosomes significantly reduced the levels of blood urea nitrogen (BUN), serum creatinine (SCR), and urinary albumin and creatinine (ACR) and 8-isoprostane. UCMSCs-derived exosomes also improved the atrophy of the kidney and glomerulus, decreased kidney pro-inflammatory factors expression (mRNA of II-1β, II-6, Tnf-α, and Mcp-1) and oxidative stress (malondialdehyde), and increased glutathione level. However, F4/80 immunohistochemistry did not show significant differences between the two groups. In systemic inflammation measurement, UCMSCs-derived exosomes decreased proinflammatory factors TNF-α, IL-6, and IL-1β levels, and increased anti-inflammatory factor IL-10 level. In vitro experiments showed that UCMSCs-derived exosomes decreased the protein expression level of TNF-α and increased the protein expression level of IL-10 in M1 macrophages. UCMSCs-derived exosomes reduce kidney inflammation and oxidative stress by improving systemic inflammation, and thus reduce kidney damage and improve kidney function. This study shows the potential application value of exosomes in the treatment of renal failure.

Abstract.Patients with acute pulmonary thromboembolism (APTE) have a high short-term mortality rate. The current study aimed to investigate the use of D-dimer in the diagnosis of APTE in suspected APTE patients. All suspected APTE patients were classified into diagnosis or control groups according to the results of a computed tomography pulmonary angiogram. Mann-Whitney U and Kruskal-Wallis H tests were used to evaluate the association between D-dimer values and APTE. Area under the curve (AUC) values and the Youden Index were used to determine D-dimer cut-off levels for the prediction of APTE. The data of 112 suspected APTE patients (54.8% women; mean age, 70.5 years) were analyzed prospectively. There were no significant differences in age (74.5 vs. 73.5 years, P=0.538) or gender distribution (female ratio 56.5 vs. 53.0%, P=0.847) between the diagnosis and control groups. The incidence of symptoms including dyspnea (67.4 vs. 33.3%; P<0.01), chest distress (47.8 vs. 25.8%; P<0.05) and elevated D-dimer (8.49 vs. 0.97 mg/l; P<0.001) were significantly higher in patients with APTE compared with the control group. D-dimer values >3.32 mg/l fibrinogen equivalent units (FEU) were indicative of APTE and the Youden Index was 0.69. The maximum AUC was 0.87 (95% CI: 0.79-0.92), the sensitivity and specificity were 89.13 and 80.30%, respectively, the positive and negative likelihood ratios were 4.53 and 0.14, respectively, and the positive and negative predictive values were 75.90 and 91.40%, respectively. A D-dimer value <0.60 mg/l FEU was the optimal threshold for excluding APTE diagnosis, with a sensitivity of 100.0% and a specificity of 28.79%. The positive and negative likelihood ratios were 1.40 and 0.00, respectively, and the positive and negative predictive values were 49.50 and 100.00%, respectively. Thus, D-dimer levels, combined with clinical assessment, yield high sensitivity and specificity in diagnosing APTE. IntroductionPulmonary thromboembolism (PTE) is a pulmonary circulation dysfunction caused by thrombotic occlusion of the pulmonary artery (1-3). Acute PTE (APTE) is a cardiovascular emergency associated with high morbidity and mortality (4-9). Computed tomography pulmonary angiogram (CTPA) is the gold standard for APTE diagnosis, with a sensitivity of 90% and a specificity of 78-100% (10-12). However, CTPA is an expensive procedure and has some technical limitations, which restrains its clinical application in many hospitals. A plasma D-dimer test is commonly the first step in patient APTE risk assessment, and is considered to have clinical value (13-15).D-dimer is a soluble degradation product of crosslinked fibrin under the action of the fibrinolytic system. An elevated concentration of D-dimer is often suggestive of secondary fibrinolytic hyperthyroidism (15). The high negative predictive value of plasma D-dimer makes it an important criterion for excluding PTE diagnosis. However, since elevated concentrations of D-dimer are associated with a variety of diseases, its diagnosis specificity for PTE is ...