Assessment of extravascular lung water by measuring the number of pulmonary ultrasound B-lines before and after CBP in patients with MODS.

ABSTRACT: To determine whether the change in the number of pulmonary ultrasound B-line can accurately assess the extravascular lung water (EVLW) before and after continuous bedside blood purification (CBP) in patients with multiple organ dysfunction syndrome (MODS).Seventy-six patients with MODS who underwent CBP were examined within 24 hours before and after CBP using pulmonary ultrasound to detect the number of ultrasound B-line or using pulse indicator continuous cardiac output method to examine extravascular lung water, blood oxygenation index, and B-type natriuretic peptide (BNP) content. The correlation of the change in the number of B lines before and after CBP treatment with the negative balance of 24 hours liquid, the change of oxygenation index, and BNP content were analyzed.In the 76 patients, CBP treatment significantly decreased EVLW, the number of B-line, and BNP (P < .05 for all), while it significantly increased the oxygenation index (P < .05). Correlation analysis showed that the decrease in B-line number after CBP treatment was positively correlated with the 24 hours negative lung fluid balance, decrease of EVLW, oxygenation index improvement, and decreased BNP content. The change in the numbers of pulmonary ultrasound B-line can accurately assess the change of EVLW before and after CBP treatment and reflect the efficiency of ventilation in the lungs and the risk of heart failure.Thus, it can replace pulse indicator continuous cardiac output as an indicator for evaluating EVLW in patients with MODS treated with CBP.

L-lysine ameliorates sepsis-induced acute lung injury in a lipopolysaccharide-induced mouse model.

Sepsis is a severe, life-threatening condition caused primarily by the cellular response to infection. Sepsis leads to increased tissue damage and mortality in patients in the intensive care unit. L-Lysine is an essential amino acid required for protein biosynthesis and is abundant in lamb, pork, eggs, red meat, fish oil, cheese, beans, peas, and soy. The present study investigates the protective effect of L-lysine against sepsis-induced acute lung injury (ALI) in a lipopolysaccharide-induced mouse model. In the present study, mice were divided into sham, control, 5 mg/kg body weight L-lysine, and 10 mg/kg body weight L-lysine treatment groups. At the end of the treatment period, we determined the levels of oxidative and inflammatory markers, myeloperoxidase (MPO) and catalase activities, total cell count, the wet/dry ratio of lung tissue, and total protein content. The effects of L-lysine on the cellular architecture of lung tissue were also evaluated. L-Lysine treatment significantly reduced the magnitude of lipid peroxidation; total protein content; wet/dry ratio of lung tissue; tumor necrosis factor alpha, interleukin-8, and macrophage inhibitory factor levels; MPO activity; and total cell, neutrophil, and lymphocyte counts. It also increased the levels of reduced glutathione and the activities of glutathione peroxidase, superoxide dismutase, and catalase. A normal cellular architecture was noted in mice in the sham group, whereas proinflammatory changes such as edema and neutrophilic infiltration were detected in mice in the control group. L-lysine significantly ameliorated these proinflammatory changes. Taking all these data together, it is suggested that the L-lysine was effective against sepsis-induced ALI.

Sirtuin 6 overexpression relieves sepsis-induced acute kidney injury by promoting autophagy.

Sirtuin 6 (SIRT6) has the function of regulating autophagy. The aim of this study was to investigate the mechanism through which SIRT6 relieved acute kidney injury (AKI) caused by sepsis. The AKI model was established with lipopolysaccharides (LPS) using mice. Hematoxylin-eosin (HE) staining and streptavidin-perosidase (SP) staining was used to observe kidney tissue and test SIRT6 and LC3B proteins in kidney. Enzyme-linked immunosorbent assay (ELISA) was performed to detected the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations. Cell counting kit-8 (CCK-8) assay and flow cytometry were carried out to test the cell viability and apoptosis rate respectively. Protein and mRNA were determined by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). AKI induced by LPS had self-repairing ability. At 12 h after modeling, the expression levels of TNF-α, IL-6, SIRT6 and LC3B-II/LC3B-I were first significantly increased and were then significantly decreased at 48 h after modeling. LPS inhibited the growth of HK-2 cells and promoted the expressions of TNF-α, IL-6, SIRT6 and LC3B. Overexpression of SIRT6 down-regulated the secretion of TNF-α and IL-6 induced by LPS. SIRT6 overexpression inhibited apoptosis induced by LPS and promoted autophagy in HK-2 cells. Silencing of the SIRT6 gene not only promoted the secretion of TNF-α and IL-6 by HK-2 cells, but also promoted apoptosis and reduced autophagy. LPS up-regulated the expression of SIRT6 gene in HK-2 cells. Overexpression of the SIRT6 gene could inhibit apoptosis and induce autophagy, which might be involved in repairing kidney damage caused by LPS.

Biological effects of autophagy in mice with sepsis-induced acute kidney injury.

This study investigated whether autophagy is activated after sepsis-induced acute kidney injury (AKI) and explored its biological role. Seventy-two normal C57 mice were randomly divided into sham operation group, cecal ligation and puncture (CLP) group and CLP+3-MA (autophagy inhibitor) group; 24 mice in each group. Mice in CLP and CLP+3-MA group were treated with cecal ligation to establish sepsis, while mice in sham operation group were treated with the same surgical operations, but not cecal ligation. Blood samples were collected from 12 mice of each group and the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were measured. The pathological changes were observed. The remaining 12 mice in each group were kept and the survival rate was recorded. Changes in the expressions of autophagy-related proteins were detected by reverse transcription-semi-quantitative PCR and western blotting. The results revealed that the levels of Cr and BUN in CLP and CLP+3-MA group were significantly higher than those in sham operation group (P<0.05), and the levels of Cr and BUN in CLP+3-MA group were higher than those in CLP group (P<0.05). The pathological score of renal injury in CLP+3-MA group was significantly higher than that of CLP group (P<0.01). The expression levels of Beclin1 and LC3-II/I were significantly increased in CLP group compared to sham operation group (P<0.01), while the expression of p62 was decreased (P<0.01). After 3-MA treatment the expression levels of Beclin1 and LC3-II/I were decreased, compared with CLP group, but accumulation of p62 occurred, and the degree of renal injury was increased. In conclusion, AKI induced by sepsis in mice can induce apoptosis and activate autophagy. The activation of autophagy aggravates the renal injury in mice, which in turn inhibits AKI after sepsis.

Expression changes of autophagy-related proteins in AKI patients treated with CRRT and their effects on prognosis of adult and elderly patients.

BACKGROUND: Sepsis is one of the common death factors in intensive care unit, which refers to the systemic inflammatory response syndrome caused by infection. It has many complications such as acute renal injury, shock, multiple organ dysfunction, and failure. The mortality of acute renal injury is the highest among the complications, which is a serious threat to the safety of patients and affects the quality of life. This study aimed to observe the changes in autophagy-related protein expressions in patients with acute kidney injury (AKI) after continuous renal replacement therapy (CRRT) and their impacts on prognosis. METHODS: 207 AKI patients visiting the Emergency Department of The First People's Hospital of Xuzhou from January 2014 to February 2018 were recruited and treated with CRRT. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to detect the expression of autophagy-related genes, including light chain 3 type II (LC3-II), autophagy-related 5 (Atg-5) and Beclin-1, in the monocytes of the patient's peripheral blood before and after treatment. The levels of inflammatory mediators interleukin (IL)-1ß and IL-6 were determined via enzyme-linked immunosorbent assay before and after treatment. The patient's serum creatinine (Scr) level before and after treatment was measured using a full-automatic biochemistry analyser. Moreover, the treatment effect was graded after CRRT, and the relationship between the prognosis of patients and the autophagy-related proteins was observed. RESULTS: The Scr levels in the patients were significantly decreased after treatment with CRRT. Before treatment, the IL-1ß and IL-6 blood levels were high in the patients, while the amounts were significantly reduced after CRTT. The expressions of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients after treatment were significantly decreased compared with those before treatment. Compared with those in survived patients, the expression of autophagy-related proteins was significantly elevated in in patients died after one to three weeks after the treatment. IL-1ß, IL-6, LC3-II and Beclin-1, but not Atg-5 values were significantly correlated with Scr. CONCLUSION: The expression of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients may change prominently after treatment with CRRT, so they are expected to be regarded as new prognostic indicators for AKI patients.

Comparison of efficiency of inhaled and intravenous corticosteroid on pregnant women with COPD and the effects on the expression of PCT and hs-CRP.

The efficiency of inhaled and systemic corticosteroids on pregnant women with chronic obstructive pulmonary disease (COPD) was investigated. The study also compared the effects of the administration on the expression of inflammatory mediator procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP). A total of 120 pregnant COPD patients were recruited and randomly allocated into the following three groups: Intravenous corticosteroid treatment group (n=42), inhaled corticosteroid treatment group (n=38), and control group (without any corticosteroid treatment, n=40). Patients of the all three groups received symptomatic supportive treatments including oxygen therapy, anti-infection therapy, expectorant, and bronchodilator. The serum PCT and hs-CRP expression levels were measured before treatment and after 7 days of treatment. Moreover, the clinical parameters such as symptoms, blood gas analysis parameters, pulmonary function indexes, fasting blood glucose (FBG) and adverse reactions were recorded. The overall clinical effective rates of the group received budesonide inhalation and the group receiving systemic methylprednisolone treatment were comparable. Both treatments were able to reduce the levels of inflammatory mediators, hs-CRP and PCT. On the other hand, treatments increased PaO2 of arterial blood gas while reducing PaCO2, thereby improving the lung function (FEV1% pred and FEV1/FVC) (P>0.05). The study observed that the FBG levels in COPD patients receiving systemic corticosteroid treatment were significantly increased, while budesonide inhalation did not significantly affect the FBG levels. In addition, rates of adverse events (such as mouth dry, oral ulcers, hoarseness) of systemic corticosteroid treatment group were significantly higher than those in inhaled corticosteroid treatment group and control group (38.1% vs. 17.5% vs. 5.0%, comparison between groups: P<0.05). In conclusion, inhaled and systemic use of corticosteroid both significantly improved dyspnea and other clinical symptoms of pregnant COPD patients by increasing oxygen partial pressure, correcting hypoxemia, and enhancing lung function. Moreover, fewer adverse reactions were observed with inhaled corticosteroid treatment, suggesting that inhaled administration is a relatively good, safe and effective treatment for pregnant COPD patients.

Evaluation of CRRT effects on pyemic secondary AKI by serum cartilage glycoprotein 39 and Annexin A1.

The aim of the present study was to examine the effects of continuous renal replacement therapy (CRRT) on pyemic secondary acute kidney injury (AKI) by serum cartilage glycoprotein 39 (YKL-40) and Annexin A1. From October, 2013 to October, 2015, 45 pyemic secondary AKI cases and 40 pyemic non-secondary AKI cases were selected for the present study. There were also 35 cases of physical examination volunteers. The serum YKL-40 and Annexin A1 levels were compared. CRRT was applied to pyemic secondary AKI patients and based on the obtained results the patients were divided into the success and failure groups. YKL-40, Annexin A1, hs-CRP, creatinine and urea nitrogen levels after 1, 6, 12, 24, 48 and 72 h of AKI were measured. The YKL-40 and Annexin A1 levels in the pyemic secondary AKI group were significantly higher than those in other two groups and differences were statistically significant (P<0.05). There was no statistically significant difference regarding time period for applying CRRT in the success and failure groups (P>0.05). The peak level of YKL-40 and Annexin A1 in the success group decreased more rapidly compared to the failure group and the difference was statistically significant (P<0.05). When the differences in creatinine and urea nitrogen levels at different time points were compared between the success and failure groups, no statistical significance was observed (P>0.05). However, the success group showed a significantly lower level compared to the failure group at 72 h. Comparisons for other time periods showed no statistical significance (P>0.05). Thus, the serum cartilage glycoprotein 39 and Annexin A1 level were able to predict the clinical effects of CRRT on pyemic secondary AKI.

Real-time three-dimensional echocardiographic evaluation of left ventricular systolic synchronicity in patients with chronic heart failure: comparison with tissue Doppler imaging.

BACKGROUND: To investigate the clinical value of real-time three-dimensional echocardiography (RT-3DE) for assessing of left ventricular systolic synchronicity. METHODS: Thirty healthy volunteers and 62 patients with congestive heart failure (CHF) were enrolled. The SD of time to peak systolic motion (TDI-Ts12-SD) was measured with tissue Doppler imaging in 12 myocardial segments. The SD and maximal difference of the time to minimal systolic volume (Tmsv) between 16, 12, or 6 myocardial segments, expressed as a percentage of cardiac cycle duration, were measured with RT-3DE and labeled Tmsv16-SD%, Tmsv12-SD%, Tmsv6-SD%, Tmsv16-D%, Tmsv12-D%, and Tmsv6-D%, respectively. The Spearman coefficient and Kappa value were calculated, and Bland-Altman analysis was performed to investigate the correlation and agreement between the two methods. Tmsv values were compared with ejection fraction (EF). RESULTS: There was a moderately positive (p< 0.01) correlation between TDI-Ts12-SD and Tmsv16-SD%, Tmsv12-SD%, Tmsv16-D%, and Tmsv12-D% (r = 0.65, 0.64, and 0.65, respectively, with Kappa values of 0.66, 0.65, 0.72, and 0.74, respectively, p< 0.01). Tmsv16-SD%, Tmsv12-SD%, and Tmsv12-D% were significantly different between CHF patients with EF ≤ 35% and those with EF > 35%. CONCLUSIONS: RT-3DE can be used in patients with CHF to quantify left ventricular mechanical dyssynchrony. Tmsv12-SD% and Tmsv12-D% were the best indices of left ventricular systolic synchronicity in relation to the severity of CHF as evaluated from EF.