Artesunate alleviates the inflammatory response of ulcerative colitis by regulating the expression of miR-155.

CONTEXT: Ulcerative colitis (UC) is a recrudescent and chronic inflammatory disease. Artesunate (ART) has shown its anti-inflammatory and antioxidative properties in severe diseases, including UC. OBJECTIVE: The present study investigates the molecular mechanisms for effects of ART on UC, and the role of miR-155 in this process. MATERIALS AND METHODS: The in vitro UC model was established by using lipopolysaccharide (LPS)-induced RAW264.7 cells. For BALB/c mice model, different concentrations/doses of ART were treated once a day for 7 days. The apoptosis and viability were measured by CCK-8 and flow cytometry assay, respectively. The expressions and concentrations of inflammatory factors were detected by qRT-PCR and ELISA, respectively. Colon tissues of mice were used for detecting the activity of MPO, and the histological changes were observed by H&E staining. RESULTS: The IC50 of ART for RAW264.7 cells was 107.3 µg/mL. In LPS-induced cells, ART treatment inhibited the cell apoptosis and promoted cell viability compared with the model group. Besides, ART treatment also reduced the expressions of pro-inflammatory factors and miR-155. However, overexpression of miR-155 showed opposite effects and attenuated the effects of ART. Meanwhile, inhibiting miR-155 expression also improved the inflammatory response induced by LPS. In UC mice model, ART treatment also alleviated the mice's survival and alleviated the inflammatory response. In addition, the expression of p-NF-κB was suppressed by ART. CONCLUSION: ART reduced the inflammatory response by inhibiting the expression of miR-155 in UC to inhibit the NF-κB pathway. This research showed ART might have potential in UC treatment.

MiR-155 aggravated septic liver injury by oxidative stress-mediated ER stress and mitochondrial dysfunction via targeting Nrf-2.

OBJECTIVE: Liver is uniquely vulnerable during sepsis. MicroRNA-155 (miR-155) is confirmed to play crucial roles in septic liver injury. The present study aims to investigate the mechanisms of miR-155 in septic liver injury. METHODS: The sepsis model was established by intraperitoneal injection of lipopolysaccharide (LPS) in mice. Mice were divided into four groups: Vehicle, miR-155 antagomir, LPS, LPS+ miR-155 antagomir. The survival rate and body weight were monitored. Liver injury was assessed by H&E staining. The levels of serum ALT and inflammatory cytokines were determined by ELISA kits. Oxidative stress was detected by MDA and SOD detection kits. The miR-155, Nrf-2, and markers related to oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial injury and apoptosis were detected by western blotting and qPCR. Apoptosis in liver tissues was detected by TUNELstaining. RESULTS: MiR-155 antagomir alleviated liver injury as evidenced by enhancing survival rate and body weight, inhibiting inflammatory cell infiltration, liver cells necrosis and decreasing ALT level. The productions of TNF-α, IL-6 were suppressed, while anti-inflammatory cytokine IL-10 was promoted by miR-155 antagomir. Oxidative stress was inhibited by miR-155 antagomir via enhancing nuclear factor, erythroid 2-like 2 (Nrf-2) expression. ER stress and Cytochrome C (Cyto-C) release were restrained by miR-155 antagomir. Sepsis-induced apoptosis was repressed by miR-155 antagomir as manifested by the decreased levels of Bax, cleaved caspase-12, 9 and 3, and increased levels of Bcl-2 and uncleaved PARP. CONCLUSION: MiR-155 antagomir relieved septic liver injury through inhibiting oxidative stress-mediated ER stress, mitochondrial dysfunction and apoptosis via targeting Nrf-2, suggesting miR-155 as a therapeutic target for septic liver injury.

PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in Non-small cell lung cancer.

AIM: This study intented to clarify the intracellular effect of PAI-1 on Non-small cell lung cancer (NSCLC) metastasis and the precise mechanism involved. METHODS: The metastatic properties of NSCLC cells were determined by transwell assays and wound-healing assay in vitro. The mRNA and protein expressions of genes were analyzed by Real-time qPCR and western blot, respectively. Pulmonary metastasis model of NSCLC cells was established to evaluate the pro-metastasis effect of PAI-1 and anti-metastatic effect of miR-34a in vivo. The gene targets of miR-34a were confirmed by luciferase reporter assays. Chromatin immunoprecipitation assay was employed to detect the transcriptional regulation of miR-34a. Co-immunoprecipitation assay was performed to observe the interaction of proteins. RESULTS: PAI-1, which was elevated in NSCLC patients with recurrence and metastasis, augmented NSCLC metastasis and was negatively related to the prognosis of NSCLC. miR-34a, which was decreased in NSCLC patients with metastasis, attenuated NSCLC metastasis and was positively correlated with the prognosis of NSCLC. Moreover, PAI-1 was identified as the target gene of miR-34a and activated the Stat3 signaling pathway to promote epithelial-mesenchymal transition (EMT) in NSCLC cells. PAI-1 interacted with PIAS3 to regulate Stat3-dependent gene expression and miR-34a was transcriptionally suppressed by Stat3 to form a positive regulatory loop through Stat3 signaling. CONCLUSION: Our findings suggest that PAI-1 and miR-34a, which can be clinically utilized as biomarkers for the clinical prognosis or diagnosis of NSCLC, are potential targets for the treatment of NSCLC.

Use of noninvasive ventilation in immunocompromised patients with acute respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory failure (ARF) remains a common hazardous complication in immunocompromised patients and is associated with increased mortality rates when endotracheal intubation is needed. We aimed to evaluate the effect of early noninvasive ventilation (NIV) compared with oxygen therapy alone in this patient population. METHODS: We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane database up to 25 July 2016. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in immunocompromised patients managed with NIV or oxygen therapy alone. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS: Five RCTs with 592 patients were included. Early NIV significantly reduced short-term mortality (RR 0.62, 95% CI 0.40 to 0.97, p = 0.04) and intubation rate (RR 0.52, 95% CI 0.32 to 0.85, p = 0.01) when compared with oxygen therapy alone, with significant heterogeneity in these two outcomes between the pooled studies. In addition, early NIV was associated with a shorter length of ICU stay (MD -1.71 days, 95% CI -2.98 to 1.44, p = 0.008) but not long-term mortality (RR 0.92, 95% CI 0.74 to 1.15, p = 0.46). CONCLUSIONS: The limited evidence indicates that early use of NIV could reduce short-term mortality in selected immunocompromised patients with ARF. Further studies are needed to identify in which selected patients NIV could be more beneficial, before wider application of this ventilator strategy.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

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.

Dehydrogenation of Formic Acid at Room Temperature: Boosting Palladium Nanoparticle Efficiency by Coupling with Pyridinic-Nitrogen-Doped Carbon.

The use of formic acid (FA) to produce molecular H2 is a promising means of efficient energy storage in a fuel-cell-based hydrogen economy. To date, there has been a lack of heterogeneous catalyst systems that are sufficiently active, selective, and stable for clean H2 production by FA decomposition at room temperature. For the first time, we report that flexible pyridinic-N-doped carbon hybrids as support materials can significantly boost the efficiency of palladium nanoparticle for H2 generation; this is due to prominent surface electronic modulation. Under mild conditions, the optimized engineered Pd/CN0.25 catalyst exhibited high performance in both FA dehydrogenation (achieving almost full conversion, and a turnover frequency of 5530 h(-1) at 25 °C) and the reversible process of CO2 hydrogenation into FA. This system can lead to a full carbon-neutral energy cycle.

An aqueous rechargeable formate-based hydrogen battery driven by heterogeneous Pd catalysis.

The formate-based rechargeable hydrogen battery (RHB) promises high reversible capacity to meet the need for safe, reliable, and sustainable H2 storage used in fuel cell applications. Described herein is an additive-free RHB which is based on repetitive cycles operated between aqueous formate dehydrogenation (discharging) and bicarbonate hydrogenation (charging). Key to this truly efficient and durable H2 handling system is the use of highly strained Pd nanoparticles anchored on graphite oxide nanosheets as a robust and efficient solid catalyst, which can facilitate both the discharging and charging processes in a reversible and highly facile manner. Up to six repeated discharging/charging cycles can be performed without noticeable degradation in the storage capacity.

Development of a nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis.

In this study, we aimed to investigate the risk factors associated with in-hospital mortality in patients with cirrhosis and sepsis, establish and validate the nomogram. This retrospective study included patients diagnosed with liver cirrhosis and sepsis in the Medical Information Mart for Intensive Care IV (MIMIC-IV). Models were compared by the area under the curve (AUC), integrated discriminant improvement (IDI), net reclassification index (NRI) and decision curve analysis (DCA). A total of 1,696 patients with cirrhosis and sepsis were included in the final cohort. Our final model included the following 9 variables: age, heartrate, total bilirubin (TBIL), glucose, sodium, anion gap (AG), fungal infections, mechanical ventilation, and vasopressin. The nomogram were constructed based on these variables. The AUC values of the nomograms were 0.805 (95% CI 0.776-0.833), which provided significantly higher discrimination compared to that of SOFA score [0.684 (95% CI 0.647-0.720)], MELD-Na [0.672 (95% CI 0.636-0.709)] and ABIC [0.674(95% CI 0.638-0.710)]. We established the first nomogram for predicting in-hospital mortality in patients with liver cirrhosis and sepsis based on these factors. This nomogram can performs well and facilitates clinicians to identify people at high risk of in-hospital mortality.

High-Q modes in defected microcircular resonator confined by metal layer for unidirectional emission.

Defected circular resonators laterally confined by a metal layer with a flat side as an emitting window are numerically investigated based on the boundary element method for realizing unidirectional emission microlasers. The results indicate that Fabry-Pérot (FP) modes become high Q confined modes in the defected circular resonator with a metallic layer. The mode coupling between the FP mode and chaotic-like mode can result in high Q confined mode for unidirectional emission with a narrow far field pattern.

New Attempts to Inhibit Methicillin-Resistant Staphylococcus aureus Biofilm? A Combination of Daptomycin and Azithromycin.

Objective: To investigate the antibacterial impact of daptomycin and azithromycin in vitro on methicillin-resistant Staphylococcus aureus (MRSA) biofilm. Methods: (1) Measure the strain growth curve and the biofilm formation curve. (2) Determine the minimum inhibitory concentrations (MICs) of daptomycin and azithromycin. (3) Investigate the antibacterial impact of the combination of daptomycin and azithromycin. (4) Perform the evaluation of the intervention impact of antimicrobial agents on MRSA biofilm. (5) Observe the biofilm after intervention with the antibacterial agent. Results: (1) MRSA exhibited three phases: lag phase (0-4 h), logarithmic growth (4-8 h) and stationary phase after 18 h; its biofilm began to form at 6 h, semi-matured at 24 h, and reached maturity after 48 h. (2) The MICs of daptomycin and azithromycin were 8 µg/mL and greater than 256 µg/mL, respectively. (3) The combination of daptomycin and azithromycin has an additive effect on MRSA (Fractional Inhibitory Concentration Index [FICI] 0.625) (FICI = MIC of drug A in combination/MIC of drug A alone + MIC of drug B in combination/MIC of drug B alone). Evaluation criteria: Synergistic effect is considered when FICI ≤ 0.5; additive effect is considered when 0.5 < FICI ≤ 1; irrelevant effect is considered when 1 < FICI ≤ 2; antagonistic effect is considered when FICI > 2). (4) Daptomycin or azithromycin at MICs inhibited not only the growth of planktonic bacteria but also the formation of biofilm. (5) The combination of both, in which group the ratio of live/dead bacteria is low and the biofilm morphology was incomplete, was more productive than monotherapy in against biofilm. Conclusion: Both daptomycin and azithromycin have anti-MRSA biofilm activity, and daptomycin is dominant. The fact that the combination of both can significantly inhibit the further maturation of MRSA biofilm and destroy already formed biofilm demonstrates the superiority of the combination over the monotherapy.

Coherence of a single mode InAlGaAs/InP cylinderical microlaser with two output ports.

We experimentally investigate the coherence of a single mode InAlGaAs/InP cylindrical microlaser with two output waveguides. For a cylindrical microlaser with a radius of 15 µm and two 2 µm-wide output waveguides, single mode operation with a side mode suppression ratio of 30 dB is realized, and a far-field interferometric pattern similar to a Young's interferometer is observed. The results indicate that the microlasers with two output waveguides can be used as the light source for an optical sensor by monitoring the phase change of the output emission from one port versus that of the other port.

Wide-angle emission and single-mode deformed circular microlasers with a flat side.

We demonstrate wide-angle emission and single mode operation in deformed circular microlasers with a flat side. The mode characteristics of a metallic confined deformed circular resonator with a flat side are investigated by finite-difference time-domain simulation. The numerical results indicate that this structure is suitable to realize wide-angle emission. Furthermore, metallic confined deformed circular microlasers with a flat side are fabricated using common photolithography and inductively coupled-plasma etching techniques. A continuous-wave single-mode operation with a side mode suppression ratio of 25 dB is achieved at an injection current of 4 mA for an 8 µm radius microlaser with a flat side. Additionally, wide angle emission over 120° is observed from the far-field pattern.

Optical bistability in GaInAsP/InP coupled-circular resonator microlasers.

Optical bistability is realized in GaInAsP/InP coupled-circular resonator microlasers, which are fabricated by planar technology. For a coupled-circular resonator microlaser with the radius of 20 µm and a 2 µm-wide bus waveguide, hysteresis loops are observed for the output power coupling into an optical fiber versus the cw injection current at room temperature. The laser output spectra of the upper and lower states of the hysteresis loop indicate that the bistability is related to mode competitions. The optical bistability can be explained as the mode competition between the symmetry and antisymmetry coupled modes relative to the bus waveguide.

[The effect of ulinastatin on gene expression of brain tissue in septic rat].

OBJECTIVE: To detect the differences in gene expression of brain tissue in septic rats with ulinastatin (UTI) preconditioning with DNA microarray. METHODS: Forty-five male Wistar rats were equally divided into control group, sepsis group, and UTI group by means of random number table. In UTI group the rats were treated with intramuscular injection of UTI (100 kU/kg) 1 hour before cecal ligation and puncture (CLP). In sepsis group and control group intramuscular balanced solution (5 ml/kg) instead of UTI was given. Septic rat model was reproduced by CLP. The control group underwent a simulated operation without CLP. Gene expression profile was studied by using RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat brain tissue after CLP. Then related computer software was used to screen and analyze the relationship between the sepsis/UTI group and control group. Finally, the difference between the sepsis group and UTI group was analyzed. RESULTS: In 22 523 genes, 55 differential genes were found between sepsis group and control group, accounting for 0.244%. Among them 47 genes showed down-regulation, with 23 known functional genes; 8 genes showed up-regulation, with 6 known functional genes. Eighty-two differential genes were found between UTI group and control group, accounting for 0.364%. Among them 66 genes showed down-regulation, with 39 known functional genes; 16 genes showed up-regulation, with 8 known functional genes. When sepsis group and UTI group compared with control group, 19 genes showed the same degree of regulation,with 18 genes (Adora2a, Avp, Cart, Gng7, Myh7, Oxt, Pde1b, Pdyn, Prkcd, Prkch, Rgs9, Rxrg, Six3, Slc17a6, Slco1a5, Sostdc1, Tac1, Ttr) showed down-regulation and 1 gene (S100a8) showed up-regulation. CONCLUSION: UTI preconditioning can partly adjust abnormal expression of genes in the brain tissue of rat with sepsis in the presence of excessive inflammation and immune suppression. UTI has some degree of protective effect on brain at the genetic level. Meanwhile, there is certain self regulation in the body during sepsis.

[Effect of ulinastatin preconditioning on gene expression profile of heart tissue in a rat sepsis model].

OBJECTIVE: To observe the regulatory effect of ulinastatin (UTI) preconditioning on gene expression of heart tissue in septic rats by DNA microarrays. METHODS: Forty-five male Wistar rats were equally divided into control group, sepsis group and UTI group by means of random number table. Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model. The control group only experienced a simulated operation without CLP. In UTI group the rats were treated with intramuscular injection of UTI 100 kU/kg 1 hour before CLP. In sepsis group and control group balanced electrolyte solution (5 ml/kg) was given. Gene expression spectrum was studied with RatRef-12 rat gene expression profile microarray to detect the changes in gene expression pattern of rat heart tissue after CLP. Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)>2.0 or RA<0.5 were identified as differential genes, and those highly correlated to sepsis and UTI groups were screened by means of related computer software to analyze their relationship. RESULTS: In 22 523 genes, 418 differential genes were found in sepsis group compared with control group, accounting for 1.856%, and among them 200 genes showed up-regulation, with 84 known functional genes, and 43 of which only showed up-regulation in sepsis group, but normal in UTI group. Two hundred and eighteen genes showed down-regulation, with 74 known functional genes, 37 of which only showed down-regulation in sepsis group, but normal in UTI group. Two hundred and two differential genes were found in UTI group compared with control group, accounting for 0.897%, and among them 111 genes showed up-regulation, with 57 known functional genes, and 17 of which only showed up-regulation in UTI group, but normal in sepsis group. Ninety-one genes showed down-regulation, with 48 known functional genes, 18 of which only showed down-regulation in UTI group, but normal in sepsis group. Compared with the control group, in both UTI group and sepsis group, 41 of known functional genes showed up-regulation, and 37 showed down-regulation. CONCLUSION: UTI preconditioning can ameliorate the damage to heart tissue in rat sepsis model, thus it has a protective effect on heart, and its mechanism may be attributable to regulatory effect of UTI on expression of stress reaction, cell signal transduction, energy metabolism, immune reaction and other related genes.

[Effects of reduced glutathione on plasma level of cytokines and pulmonary ultrastructure in rats with sepsis].

OBJECTIVE: To investigate the protection mechanism of reduced glutathione (GSH) in acute lung injury in rats with sepsis. METHODS: Sepsis in Sprague-Dawley (SD) rats were reproduced by cecal ligation and puncture (CLP). They were randomly divided into four groups, sham-operated group, model group, GSH treatment group and levofloxacin (LEV) treatment group. Heart blood of 7 rats in all groups was collected at 3, 6, 12, 24 hours after operation. The plasma levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. The lung ultrastructure changes were observed with electron microscope at 24 hours in all groups. RESULTS: Compared with the sham-operated group, the plasma level of TNF-alpha increased more obviously at 6 hours of the model group [(227+/-28) microg/L vs. (132+/-9) microg/L, P<0.01]. Compared with the model group, the plasma level of TNF-alpha in the GSH treatment group decreased obviously [(144+/-28) microg/L], and it was obviously lower than that of LEV treatment group [(214+/-48) microg/L , both P<0.01] . No obvious difference of plasma level of TNF-alpha was found at 3, 12, 24 hours among all the groups. Compared with the sham-operated group, the plasma level of IL-6 of the model group raised obviously at 3 hours [(267.65+/-72.87) microg/L vs. (135.43+/-40.08) microg/L, P<0.01]. In the GSH treatment group, the plasma level of IL-6 [(191.97+/-62.98) microg/L] was lower than that of the model group and the LEV treatment group [(268.75+/-74.67) microg/L, both P<0.05]. The plasma level of IL-6 was not obviously different among all groups at 6, 12, 24 hours. In the model group, the injury of pulmonary ultrastructure was obvious, especially in the mitochondria of the pulmonary cells. In the GSH treatment group, the change in ultrastructure of the lung was slight. CONCLUSION: TNF-alpha and IL-6 play significant role in the development of pulmonary ultrastructure injury in acute lung injury of septic rats. Treatment with GSH was effective in preventing such injury.

[Effect of ulinastatin preconditioning on gene expression profile of kidney tissue in a rat sepsis model].

OBJECTIVE: To investigate the modulation effect of ulinastatin (UTI) preconditioning on gene expression of kidney tissue in septic rats by DNA microarrays. METHODS: Forty-five male Wistar rats were divided into control group, sepsis group and UTI group, with 15 rats in each group by means of random number table. Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model. The control group only experienced a simulated operation without CLP. In UTI group the rats were treated with intramuscular injection of UTI (100 kU/kg). In sepsis group and control group intramuscular balanced solution (5 ml/kg) was given. Gene expression spectrum was studied with oligonucleotide gene expression profile microarray that contained 22 523 rat cDNA clones to detect the changes in gene expression pattern of rat kidney tissue 24 hours after CLP. Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)>2.0 or RA<0.5 were identified as differential genes, then those highly correlated to sepsis and UTI were screened by means of related computer software, and their relationship was analyzed. RESULTS: Three hundred and twenty-seven differential genes were found in sepsis group/control group, accounting for 1.45%, and among them 181 genes showed up-regulation,with 78 known functional genes, and 146 genes showed down-regulation, with 51 known functional genes. One hundred and twenty-seven differential genes were found in UTI group/sepsis group, accounting for 0.56%, and among them 41 genes showed up-regulation, with 14 known functional genes, and 86 genes showed down-regulation, with 37 known functional genes. Twenty-two genes were down-regulated in sepsis group/control group but up-regulated in UTI group/sepsis group, with 11 known functional genes, 51 genes were up-regulated in sepsis group/control group but down-regulated in UTI group/sepsis group, with 24 known functional genes. CONCLUSION: UTI preconditioning can alleviate the damage of kidney tissue in rat sepsis model, thus showing a protective effect on kidney, and the mechanism may be attributable to effect of UTI on modulation of immune reaction, energy metabolism, inflammatory reaction, signal transduction, defense reaction, oxidation-reduction reaction, DNA replication, and transcription related genes.

[An investigation of changes in gene expression profile of heart tissue in a rat sepsis model].

OBJECTIVE: To investigate the changes in gene expression spectrum of heart tissue in septic rats by DNA microarrays. METHODS: Thirty male Wistar rats were randomly divided into sepsis group and control group with 15 rats in each group. Cecal ligation and puncture (CLP) was used to reproduce rat sepsis model, and the success of reproduction was confirmed by examining the heart tissue with transmission electron microscope. Gene expression spectrum was studied with oligonucleotide gene expression profile microarray that contained 22 523 rat cDNA clones to detect the changes in gene expression pattern of rat heart tissue 24 hours after CLP. Genes with fluorescent signal of Cy3/Cy5 of ratio average (RA)>2.0 or RA<0.5 were identified as differential genes, then those that high correlated to sepsis were screened by means of related computer software, and their relationship was analyzed. RESULTS: Electron microscopic examination of heart tissue demonstrated that the sepsis model was successfully reproduced. Compared to the controls, gene expression of 418 genes of heart tissue of septic rat were changed 24 hours after CLP, accounting for 1.86%, and among them 200 genes showed up-regulation, 218 genes with down-regulation. Among known functional genes, 84 genes up-regulated and 74 genes down-regulated. They were related with a range of genetic functions, such as acute stress reaction, signal transduction, immune response, energy metabolism related genes etc. CONCLUSION: There are a series of changes in gene expression in heart tissue apparently induced by sepsis rat. DNA microarray technology provides a new tool for rapidly analyzing them.

Effects of different ascorbic acid doses on the mortality of critically ill patients: a meta-analysis.

BACKGROUND: Low levels of ascorbic acid (AA) have been detected in critically ill patients in which AA supplementation leads to promising outcomes. However, the ability of AA to reduce mortality in critically ill patients remains controversial. In this study, we have performed a meta-analysis to evaluate the effects of AA dose on the mortality of critically ill adults. METHODS: Electronic databases were searched for trials in which AA had been intravenously administered to critically ill patients regardless of the dose or the co-administration of antioxidant agents. The predefined primary outcome included all-cause mortality at final follow-up. RESULTS: The included trials enrolled a total of 1210 patients. Intravenous (IV) AA doses of 3-10 g/d reduced the mortality of critically ill patients (OR 0.25; 95% CI (0.14-0.46); p < 0.001; I2 = 0.0%), while low (< 3 g/d) and high AA doses (≥ 10 g/d) had no effect (OR 1.44; 95% CI (0.79-2.61); p = 0.234; I2 = 0.0% versus OR 1.12; 95% CI (0.62-2.03); p = 0.700; I2 = 0.0%). AA was associated with a decreased duration of vasopressor support and mechanical ventilation, but did not influence fluid requirement or urine output during the first 24 h of admission. The number of patients suffering from acute kidney injury and the length of intensive care unit or hospital stays were also unaffected by the AA. CONCLUSION: Intravenous AA reduces the duration of vasopressor support and mechanical ventilation; 3-10 g AA results in lower overall mortality rates. Given the limitations of the primary literature, further studies are required to fully clarify the effectiveness of AA during the management of critically ill patients.

Value of Kidney Disease Improving Global Outcomes Urine Output Criteria in Critically Ill Patients: A Secondary Analysis of a Multicenter Prospective Cohort Study.

BACKGROUND: Urine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr). METHODS: We conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses. RESULTS: The prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality. CONCLUSION: UO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.