[Value of urine soluble triggering receptor expressed on myeloid cells-1 in the early diagnosis of sepsis associated acute kidney injury].

Objective: To assess the value of urine soluble triggering receptor expressed on myeloid cells-1(sTREM-1) in early diagnosis and prognosis of sepsis associated acute kidney injury (AKI). Methods: This was a case-control study. A total of 62 patients with sepsis during November 2016 to June 2017 were collected, who were divided into non-AKI sepsis (n= 49) and AKI sepsis (n=13) groups according to the serum creatinine (SCr) or urine output, sepsis with shock (n=22) and sepsis without shock (n=40) groups according to the presence of shock, survival (n=47) and death (n=15) groups according to the mortality. Twenty healthy children were recruited in control group, whose urine sTREM-1 were used as reference value. Urine and blood specimens were detected on admission (within 12 h), at 24 h and 48 h after admission. Student's t-test and Mann-Whitney U test were used for statistical analysis. Results: On admission, the level of urine sTREM-1 were significantly higher in sepsis patients than in healthy controls (96.8 (71.3, 105.8) vs. 68.6 (60.6, 71.1)ng/L, Z=4.708, P<0.05). Comparing of sTREM-1 in different groups showed that the levels were higher in AKI sepsis patients than in the non-AKI ones ((106±5) vs. (86±18) ng/L, t=6.670, P<0.05), higher in the sepsis with shock group than in sepsis without shock group ((98±11) vs. (86± 20) ng/L, t=3.059, P<0.05), and also higher in death group than in survival group ((101±12) vs. (87±18) ng/L, t=3.615, P<0.05). The area under the receiver operating characteristic (AUROC) of urine sTREM-1 in predicting sepsis associated AKI was 0.814 (95%CI: 0.708-0.920), which was higher than that in predicting shock, increased serum creatinine, hyperlipidemia or hyperbilirubinemia (0.530, 0.425, 0.429 and 0.443, respectively). The optimal sTREM-1 cut-off point for predicting sepsis associated kidney injury was 96.5 ng/L, with specificity and sensitivity of 100% and 57.1%. The odds ratio(OR) of urine sTREM-1 was 0.879 with a significance of 0.005 after adjusting shock, prognosis, serum creatinine, lactate and total bilirubin level, indicating that the urine sTREM-1 was an independent risk factor of sepsis associated AKI. Conclusion: Urine sTREM-1 can be used as an early diagnostic biomarker for sepsis associated AKI, with advantage of noninvasiveness and convenience. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-DDD-17010743.

Quercetin decreased heart rate and cardiomyocyte Ca2+ oscillation frequency in rats and prevented cardiac hypertrophy in mice.

AIM: To study the effects of quercetin (Que) on myocardial excitation-contraction coupling and cardiac remodeling. METHODS: Left ventricles and femoral arteries of rats were cannulated for hemodynamic recording. Mouse cardiac hypertrophy was induced by abdominal aortic coarctation (AAC). Cultured myocardial cells in neonatal rats were loaded with Fura 2-AM. The intracellular calcium ([Ca2+]i) and spontaneous [Ca2+]i oscillations ([Ca2+]i-SO) were tested by AR-CM-MIC cation measurement system. RESULTS: Que 3 or 25 mg.kg-1 i.v. in rats decreased heart rate from (420 +/- 19) to (390 +/- 15) and (314 +/- 18) beat.min-1, respectively, companied with very modest changes in both left ventricular pressures (LVP) and its differential dpLV/dtmax. Que 10, 50, 250 mumol.L-1 concentration-dependently slowed the frequency of [Ca2+]i-SO in cultured myocardial cells from (26 +/- 4) to (25 +/- 3), (18 +/- 4), and (12 +/- 3) time.min-1, respectively, but did not change their resting [Ca2+]i or amplitudes of [Ca2+]i-SO. Similarly, the increases in frequency of [Ca2+]i-SO caused by either isoproterenol (Iso) or ouabain (Oua) were prevented by Que 100 mumol.L-1, while the simultaneous increases in amplitude of [Ca2+]i-SO remained. Besides, [Ca2+]i rises excited by angiotensin II (Ang II) but not high [K+]o were prevented by Que 100 mumol.L-1. Daily administration of Que 120 mg.kg-1 i.g. for 5 d markedly prevented the cardiac hypertrophy in AAC mice, without effects on the ventricular mass to body weight ratio (VM/BW) in sham-operated mice. CONCLUSION: Que decreased myocardial [Ca2+]i-oscillation frequency and prevented cardiac remodeling, but had no direct effect on cardiac excitation-contraction coupling.

[Determination of the thickness of the wall of portal vein trunk in patients of schistosomiasis japonica with hepatic fibrosis and its clinical significance].

The thickness of the wall of the portal vein trunk (PVT) was determined with B-mode ultrasonography in 82 patients of schistosomiasis, with hepatic fibrosis, 35 cases of schistosomiasis without hepatic fibrosis, 30 cases of post-hepatitis cirrhosis and 32 healthy subjects. It was shown that the wall thickness of PVT increased in all the patients with schistosomiasis. The thickness in patients of schistosomiasis with hepatic fibrosis was markedly increased as compared with the other three groups (P < 0.01 in all). The magnitude of increase of the wall thickness correlated well with the severity of the pathological change of hepatic fibrosis. It was also noted that change of wall thickness of PVT was not only accompanied by change in hyaluronate and hydroxyproline estimation, but also closely correlated with the international criteria of ultrasound parameters for assessment of pathological changes of schistosomiasis (rs = 0.839, rs = 0.748). Measurement of the wall thickness of PVT is, therefore, a valuable clinical method for diagnosing schistosomiasis with hepatic fibrosis and determining the severity of its pathological change.

Doxorubicin-induced DNA breaks, topoisomerase II activity and gene expression in human melanoma cells.

We have analyzed five human melanoma cell lines, displaying variable doxorubicin resistance (1- to 6-fold), for drug-induced DNA breaks, topoisomerase II activity and mRNA expression. Enhanced drug efflux was not the reason for doxorubicin resistance of these tumor cells although they overexpressed the transmembrane 170 kDa P-glycoprotein. Doxorubicin-induced DNA lesions (2-fold) and topoisomerase II activity (7-fold) were higher in HM-1 and G361 cells than in the less doxorubicin-sensitive NH and FCCM-9 cells. Topoisomerase II mRNA expression was also 2-fold higher in HM-1 and G361 cells. Doxorubicin-induced DNA breaks and topoisomerase II activity inversely correlated with the degree of doxorubicin sensitivity. Southern blot analysis showed variation in the hybridization pattern of topoisomerase II gene in doxorubicin-resistant cells when compared to sensitive cells. This study portrays the low doxorubicin sensitivity of NH and FCCM-9 cells as "atypical" and emphasizes the importance of DNA damage and topoisomerase II activity in cellular low doxorubicin resistance.

Doxorubicin resistance in human melanoma cells: MDR-1 and glutathione S-transferase pi gene expression.

Cellular drug resistance is believed to involve P-glycoprotein-related drug efflux as well as xenobiotic detoxification. In the present study, we analyzed five human melanoma cell lines with 1- to 6-fold doxorubicin resistance for doxorubicin retention and MDR-1 and GST pi gene expression. All the cell lines had high doxorubicin retention, and efflux blockers such as trifluoperazine and verapamil did not have a major effect on drug retention or cytotoxicity. Even though all the cell lines carried the MDR-1 and GST pi genes, gene amplification was not associated with drug resistance. Both laser flow cytometry and immunoperoxidase staining showed high expression of C-219 reactive P-glycoprotein in some of the resistant cells which was not accompanied by either high drug efflux or sensitivity to doxorubicin efflux blockers.