[Nano-silicon Dioxide Affects Apoptosis of Alveolar Macrophages via PI3K/AKt Signaling Pathway].

OBJECTIVE: To investigate the effect of phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKt) signaling pathway on the apoptosis of alveolar macrophages (AM) induced by nano-silica (NS) dust. METHODS: After exposure to different concentrations of NS suspension, CCK-8 assay was used to detect the AM viability; the cellular morphology of apoptotic AM was observed under fluorescence microscopy; the apoptosis rate and mitochondrial transmembrane potential of cells were detected by flow cytometry before and after pretreatment with phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002; Western blot was used to detect the expression of apoptosis-related proteins Bax, Bcl-2, p-PI3K and p-AKt. RESLUTS: The survival rate of AM was decreased in a time-dose relationship after NS exposure. With LY294002 pretreatment, the mitochondrial transmembrane potential level and the expressions of p-PI3K, p-AKt and Bcl-2 were decreased, the expression of Bax and the apoptosis rate were increased. CONCLUSION: Our data suggested that the activation of PI3K/AKt signaling pathway played an important role in NS-induced apoptosis in alveolar macrophages.

[Comparation of Toxic Effect of Silicious Mineral Dusts on Lung Epithelial A549 Cells].

Considering the high contents of minerals and the potential health risk of mineral dusts to human and the environment, this paper was aimed to figure out the toxic effect and mechanism of four common mineral particles (quartz, albite, sericite, and montmorillonite). Cytotoxicity assays for cell viability (MTT assay), membrane integrity (LDH assay), oxidative stress (H2O2 assay) and inflammatory cytokines (TNF-α and IL-6 assay) were applied. The results showed the influence of these mineral particles on A549 cell viability followed the order of momtmorillonite > cericite≥quartz > albite. There was no obvious relation between cell viability and the content of SiO2, however, good linear correlation with the content of iron, and the cytotoxicity of mineral dusts was strengthened with increasing iron content. Mineral dusts generated H2O2 in cell or cell-free systems. In particular, H2O2 exhibited a linear correlation with the iron content, which meant that iron in the mineral dusts played an important role in the generation of reactive radical. Among those samples, oxidative stress induced by montmorillonite was distinctly stronger, while there was negligible influence induced by quartz and albite. Besides, all the tested samples induced damage to A549 cell membrane, and triggered the release of TNF-α or IL-6, but differed by the kinds of mineral dusts. In conclusion, composition and structure directly affected, but were not the only factors that contributed to the biological activity of mineral dusts, the evaluation of cell viability, membrane damage, free radicals and inflammatory reaction induced by mineral dusts should take the external morphology, surface active groups, solubility, adsorption and ion exchange properties into consideration.

Meta-analysis of efficacy and safety of fast-track surgery in gastrectomy for gastric cancer.

BACKGROUND: Fast-track surgery (FTS) is a promising program for surgical patients and has been applied to several surgical diseases. FTS is much superior to conventional perioperative care. Our aim was to evaluate and compare the safety and efficacy of FTS and conventional perioperative care for patients undergoing gastrectomy using a systematic review. METHODS: We searched the literature in PubMed, SCOPUS, and EMBASE up to November 2013. No language restriction was applied. Weighted mean differences (WMDs) and odds ratios (ORs) with their 95 % confidence intervals (CIs) were used for analysis by a fixed or a random effects model according to the heterogeneity assumption. RESULTS: In the present meta-analysis, we included five randomized controlled trials and one controlled clinical trial from five studies. Compared with conventional care, FTS shortened the duration of flatus (WMD -21.08; 95 % CI -27.46 to -14.71, z = 6.48, p < 0.00001 in the open surgery group; WMD -8.20; 95 % CI -12.87 to -3.53, z = 3.44, p = 0.0006 in the laparoscopic surgery group), accelerated the decrease in C-reactive protein (WMD -15.56; 95 % CI 21.28 to 9.83, z = 5.33, p < 0.00001), shortened the postoperative stay (WMD -2.00; 95 % CI -2.69 to -1.30, z = 5.64, p < 0.00001), and reduced hospitalization costs (WMD -447.72; 95 % CI -615.92 to -279.51, z = 5.22, p < 0.00001). FTS made no significant difference in operation times (p = 0.93), intraoperative blood loss (p = 0.79), or postoperative complications (p = 0.07). CONCLUSIONS: Based on current evidence, the FTS protocol was feasible for gastric cancer patients who underwent gastrectomy (distal subtotal gastrectomy, proximal subtotal gastrectomy, or radical total gastrectomy) via open or laparoscopic surgery. Larger studies are needed to validate our findings.

Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats.

BACKGROUND: Sudden cardiac arrest is a leading cause of death worldwide. Three-fourths of cardiac arrest patients die before hospital discharge or experience significant neurological damage. Hydrogen-rich saline, a portable, easily administered, and safe means of delivering hydrogen gas, can exert organ-protective effects through regulating oxidative stress, inflammation, and apoptosis. We designed this study to investigate whether hydrogen-rich saline treatment could improve survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation, and the mechanism responsible for this effect. METHODS: Sprague-Dawley rats were subjected to 8 minutes of cardiac arrest by asphyxia. Different doses of hydrogen-rich saline or normal saline were administered IV at 1 minute before cardiopulmonary resuscitation, followed by injections at 6 and 12 hours after restoration of spontaneous circulation, respectively. We assessed survival, neurological outcome, oxidative stress, inflammation biomarkers, and apoptosis. RESULTS: Hydrogen-rich saline treatment dose dependently improved survival and neurological function after cardiac arrest/resuscitation. Moreover, hydrogen-rich saline treatment dose dependently ameliorated brain injury after cardiac arrest/resuscitation, which was characterized by the increase of survival neurons in hippocampus CA1, reduction of brain edema in cortex and hippocampus, preservation of blood-brain barrier integrity, as well as the decrease of serum S100ß and neuron-specific enolase. Furthermore, we found that the beneficial effects of hydrogen-rich saline treatment were associated with decreased levels of oxidative products (8-iso-prostaglandin F2α and malondialdehyde) and inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and high-mobility group box protein 1), as well as the increased activity of antioxidant enzymes (superoxide dismutase and catalase) in serum and brain tissues. In addition, hydrogen-rich saline treatment reduced caspase-3 activity in cortex and hippocampus after cardiac arrest/resuscitation. CONCLUSIONS: Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.

Effect of dopamine and metaraminol on the renal function of patients with septic shock.

BACKGROUND: Vasoactive drugs are often necessary for reversing hypotension in patients with severe infection. The standard for evaluating effects of vasoactive drugs should not only be based on the increase of arterial blood pressure, but also on the blood flow perfusion of internal organs. The effects of dopamine and metaraminol on the renal function of the patients with septic shock were investigated retrospectively in this study. METHODS: Ninety-eight patients with septic shock were divided into three groups according to the highest infusing rate of metaraminol, with the lightest infusing rate of (0.1 - 0.5, 0.6 - 1.0, > 1.0) microgxkg(-1)xmin(-1) in group A, B and C respectively. Urine output, mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB), urine beta(2)-microglubulin (Ubeta(2)-MG) and Apache III scores were recorded. RESULTS: Before antishock therapy, hypotension, tachycardia and oliguria occurred to all the 98 patients with septic shock and CRE, BUN, U-ALB, Ubeta(2)-MG and Apache III scoring were abnormal in most cases. With the antishock therapy, MAP, HR, urine output, BUN and CRE in all patients returned gradually to normal (P < 0.05 or < 0.01 compared to those before antishock therapy). U-ALB, Ubeta(2)-MG output and Apache III scoring also reverted but remained abnormal (P < 0.01 compared to those before antishock therapy). No statistically significant differences in the changes of these indices with the time existed among the three groups (P > 0.05). CONCLUSION: Dopamine and metaraminol when applied to the patients with septic shock could effectively maintain the circulatory stability and promote restoration of renal function.

[Effect of dopamine combined with norepinephrine on the renal function in patients with septic shock].

OBJECTIVE: To investigate the effects of dopamine and norepinephrine on the renal function in the patients with septic shock. METHODS: Eighty-seven patients with septic shock were divided into three groups (group A, B, C) according to the biggest infusing rate of norepinephrine, with the infusing rate of 0.5 - 0.9, 1.0 - 1.5, 1.6 - 2.0 microg x kg(-1) x min(-1), respectively. Mean arterial blood pressure (MAP), heart rate (HR), urine output, blood urea nitrogen (BUN), creatinine (CRE), urine albumin (U-ALB) and urine beta(2)-microglobulin (Ubeta(2)-MG) as well as APACHE III score in all the patients were detected. RESULTS: Before anti-shock therapy was given, hypotension, tachycardia and oliguria occurred in all the 87 patients, and CRE, BUN, U-ALB, Ubeta(2)-MG and APACHE III score were abnormal in most cases. With the anti-shock therapy, MAP, HR, urine output and BUN, CRE in all patients returned to normal levels gradually, and U-ALB, Ubeta(2)-MG levels and APACHE III score also restored but still remained abnormal. CONCLUSIONS: The first aim of treating septic shock should be restoring the organ blood supply, and based on volume resuscitation, dopamine, noradrenaline and other vasoactive drugs could be combined to maintain circulatory stability.

[Protective effect of shenfu injection against ischemia-reperfusion injury due to pancreas transplantation in rats].

OBJECTIVE: To investigate the protective effect of Shenfu Injection against ischemia-reperfusion (I/R) injury due to pancreas transplantation in rats, and explore its possible mechanism. METHODS: Six normal SD rats with sham operation were taken as the normal control group, 24 steptozozin-induced diabetic SD rats were randomly divided into 4 groups, with 6 in each group. Except I/R group, the rats in the other groups were intravenous injected with Shenfu Injection (SF,10 mg/kg), Hongshen Injection (HS, 9 mg/kg) and Fuzi Injection (FZ 1 mg/kg) respectively at the day and 30 minutes before pancreas transplantation performed in the SF group, HS group and FZ group, respectively. At the same time, rats in the normal control group and in the I/R group were intravenously injected the same volume of normal saline. The blood glucose was detected before and after reperfusion, and 2 hours later after reperfusion, the contents of serum nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha), the concentrations of malondialdehyde (MDA) , superoxide dismutase (SOD) , and myeloperoxidase (MPO) in the transplanted pancreas tissues were detected. The cell apoptosis of the transplanted pancreas tissue was determined by TUNEL, and the bcl-2 and Bax protein expression was determined by Western blot. RESULTS: After reperfusion, the levels of blood glucose and TNF-alpha decreased and the concentration of NO increased in the SF group, HS group and FZ group, compared with those in the I/R group. The activity of SOD, bcl-2 expression and the ratio of bcl-2 and Bax were higher, while the content of MDA, the activity of MPO, apoptotic indexes, and Bax expression were lower in the SF group, HS group and FZ group than those in the I/R group. CONCLUSION: Shenfu Injection can protect L/R injury due to pancreas transplantation in rats, the possible mechanism may be related to promoting activity of SOD, increasing synthesis of endogenous NO, decreasing the excretion of TNF-alpha, alleviating conglutination and aggregation of polymorphonuclear neutrophils (PMNs) in pancreas, as well as up-regulating Bcl-2 gene expression and down-regulating the Bax gene expression.