Efficacy and safety of benralizumab for eosinophilic asthma: A systematic review and meta-analysis of randomized controlled trials.

CONTEXT: Benralizumab is a humanized monoclonal antibody that targets the α chain of the IL-5 receptor (IL-5Rα) and is currently being assessed in clinical trials for asthma control. OBJECTIVE: Our systematic review and meta-analysis intends to evaluate the therapeutic efficacy and safety of benralizumab in patients with eosinophilic asthma. DATA SOURCES AND EXTRACTION: Literature searches of PubMed, Embase, and the Cochrane Library were performed to identify randomized controlled trials of benralizumab and clinic outcomes in asthmatics. RESULTS: In total, 7 articles with 2,321 subjects met our inclusion criteria. From this pooled analysis, we found that benralizumab significantly reduces exacerbations (RR: 0.63, 95% CI: 0.52-0.76, p < 0.00001; I2 = 52%, p = 0.06) compared to placebo in eosinophilic asthma. There was no statistical trend for improvement in forced expiratory volume in 1 second or asthma control indices such as Quality of Life Assessment (AQLQ) and Asthma Control Questionnaire score in benralizumab-treated patients. In addition, safety data indicated that benralizumab administration resulted no increasing incidence of adverse events and was well tolerated (RR: 1.00, 95% CI: 0.95-1.05, p = 0.96; I2 = 40%, p = 0.13). CONCLUSION: These results demonstrate the efficacy and safety of benralizumab for asthma patients with severe or uncontrolled symptoms and elevated eosinophils and provide support for benralizumab as an ideal option to treat asthma in this patient population.

Association between SOD2 C47T polymorphism and lung cancer susceptibility: a meta-analysis.

Lung cancer is one of the most common cancers worldwide, but its etiology is still unclear. Superoxide dismutase 2 (SOD2) plays an essential role in oxidative stress and may be involved in the development of lung cancer. The association between SOD2 C47T polymorphism and lung cancer risk has been widely investigated, but the results of previous studies are contradictory. We conducted a meta-analysis to comprehensively assess the association between SOD2 C47T polymorphism and lung cancer. The association was estimated by odds ratio (OR) with 95 % confidence interval (95 % CI). A total of 10 studies with 5,146 cases and 6,173 controls were identified. The results showed that SOD2 C47T polymorphism was significantly associated with lung cancer (T versus C: OR = 0.88, 95 % CI = 0.83-0.93, P < 0.001; TT versus CC: OR = 0.74, 95 % CI = 0.66-0.83, P < 0.001; TT versus CC/CT: OR = 0.81, 95 % CI = 0.73-0.89, P < 0.001). Subgroup analysis by ethnicity suggested that SOD2 C47T polymorphism was significantly associated with lung cancer in both East Asians and Caucasians. Conclusively, this meta-analysis strongly suggests that SOD2 C47T polymorphism is significantly associated with lung cancer.

Global Transformer and Dual Local Attention Network via Deep-Shallow Hierarchical Feature Fusion for Retinal Vessel Segmentation.

Clinically, retinal vessel segmentation is a significant step in the diagnosis of fundus diseases. However, recent methods generally neglect the difference of semantic information between deep and shallow features, which fail to capture the global and local characterizations in fundus images simultaneously, resulting in the limited segmentation performance for fine vessels. In this article, a global transformer (GT) and dual local attention (DLA) network via deep-shallow hierarchical feature fusion (GT-DLA-dsHFF) are investigated to solve the above limitations. First, the GT is developed to integrate the global information in the retinal image, which effectively captures the long-distance dependence between pixels, alleviating the discontinuity of blood vessels in the segmentation results. Second, DLA, which is constructed using dilated convolutions with varied dilation rates, unsupervised edge detection, and squeeze-excitation block, is proposed to extract local vessel information, consolidating the edge details in the segmentation result. Finally, a novel deep-shallow hierarchical feature fusion (dsHFF) algorithm is studied to fuse the features in different scales in the deep learning framework, respectively, which can mitigate the attenuation of valid information in the process of feature fusion. We verified the GT-DLA-dsHFF on four typical fundus image datasets. The experimental results demonstrate our GT-DLA-dsHFF achieves superior performance against the current methods and detailed discussions verify the efficacy of the proposed three modules. Segmentation results of diseased images show the robustness of our proposed GT-DLA-dsHFF. Implementation codes will be available on https://github.com/YangLibuaa/GT-DLA-dsHFF.

[Effect of chronic lead exposure on expression of autophagy-associated proteins in rat hippocampus].

OBJECTIVE: To investigate the effects of chronic lead exposure on expression of autophagy-associated proteins in rat hippocampus. METHODS: SD rats were randomly divided into three groups: control group was given distilled water, lead-exposed groups were given 0.5 g/L (low-dose) or 2.0 g/L(high-dose) lead acetate solution in drinking water. The rat pups started to drink the lead content water until 60 d maturity. The lead contents in blood and brain samples were analyzed by graphite furnace atomic absorption spectrophotometry. The expressions of Beclin 1, LC3, LAMP2 and cathepsin B proteins were detected by Western blot and immunohistochemistry. RESULTS: Compared with control group, the contents of lead were significantly higher in blood and hippocampus samples in chronic lead-exposed rats (P<0.01). Western blot showed that the expression of Beclin 1 and LC3-II/LC3-I increased significantly in high dose lead-exposed group compared with control group (P<0.05 or P<0.001). The confocal laser immunostaining results demonstrated that increased immunofluorescence staining of cathepsin B in hippocampal neurons compared with control animals. CONCLUSION: The disturbance of autophagy-lysosome signaling molecules might be partially contribute to neurotoxicity of chronic lead exposure.

Myosin light chain kinase is necessary for tonic airway smooth muscle contraction.

Different interacting signaling modules involving Ca(2+)/calmodulin-dependent myosin light chain kinase, Ca(2+)-independent regulatory light chain phosphorylation, myosin phosphatase inhibition, and actin filament-based proteins are proposed as specific cellular mechanisms involved in the regulation of smooth muscle contraction. However, the relative importance of specific modules is not well defined. By using tamoxifen-activated and smooth muscle-specific knock-out of myosin light chain kinase in mice, we analyzed its role in tonic airway smooth muscle contraction. Knock-out of the kinase in both tracheal and bronchial smooth muscle significantly reduced contraction and myosin phosphorylation responses to K(+)-depolarization and acetylcholine. Kinase-deficient mice lacked bronchial constrictions in normal and asthmatic airways, whereas the asthmatic inflammation response was not affected. These results indicate that myosin light chain kinase acts as a central participant in the contractile signaling module of tonic smooth muscle. Importantly, contractile airway smooth muscles are necessary for physiological and asthmatic airway resistance.

Melatonin ameliorates ischemic-like injury-evoked nitrosative stress: Involvement of HtrA2/PED pathways in endothelial cells.

Peroxynitrite contributes to diverse cellular stresses in the pathogenesis of ischemic complications. Here, we investigate the downstream effector signaling elements of nitrosative stress which regulate ischemia-like cell death in endothelial cells and protective effect of melatonin. When the mitochondrial membrane potential (ΔΨm) of oxygen-glucose deprivation (OGD)-treated cells was assessed using the fluorescent probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazol -carbocyanine iodide, we observed spontaneous changes in peroxynitrite formation. Concomitantly, western blot and confocal microscopy analyses indicated that prolonged OGD exposure initiates the release of mitochondrial HtrA2 and dramatically decreases phosphoprotein enriched in astrocytes (PED or PEA-15) protein levels. Consistently, cultured endothelial cells treated with peroxynitrite (1-50 µm) exhibited a concentration-dependent release of mitochondrial HtrA2 and concomitant PED degradation in vitro. Notably, HtrA2 activation coincided with increased nitrotyrosine immunoreactivity in microvessels of rats following microsphere embolism. Additionally, the protective effect of PED overexpression in OGD-induced apoptosis was abolished by transfection with the PED(S104A/S116A) mutant. Furthermore, the effect of melatonin, an potential antioxidant, on endothelial apoptotic cascade was examined in OGD-evoked nitrosative stress. Our data showed that the application of melatonin provided significant protection against OGD-induced peroxynitrite formation and mitochondrial HtrA2 release, accompanied with a decrease in degradation PED and x-linked inhibitor of apoptosis protein, which is associated with activation of the caspase cascade. Taken together, the protective effect of melatonin is likely mediated, in part, by inhibition of peroxynitrate-mediated nitrosative stress, which in turn relieves imbalance of mitochondrial HtrA2-PED signaling and endothelial cell death.

Regulation of the ischemia-induced autophagy-lysosome processes by nitrosative stress in endothelial cells.

The cellular mechanisms that underlie the diverse nitrosative stress-mediated cellular events associated with ischemic complications in endothelial cells are not yet clear. To characterize whether autophagic elements are associated with the nitrosative stress that causes endothelial damage after ischemia injury, an in vitro sustained oxygen-glucose deprivation (OGD) and an in vivo microsphere embolism model were used in the present study. Consistent with OGD-induced peroxynitrite formation, a rapid induction of microtubule-associated protein 1 light chain 3 (LC3)-I/II conversion and green fluorescent protein-LC3 puncta accumulation were observed in endothelial cells. The Western blot analyses indicated that OGD induced elevations in lysosome-associated membrane protein 2 and cathepsin B protein levels. Similar results were observed in the microvessel insult model, following occlusion of the microvessels using microsphere injections in rats. Furthermore, cultured endothelial cells treated with peroxynitrite (1-50 µm) exhibited a concentration-dependent change in the pattern of autophagy-lysosome signaling. Intriguingly, OGD-induced autophagy-lysosome processes were attenuated by PEP-19 overexpression and by a small-interfering RNA (siRNA)-mediated knockdown of eNOS. The importance of nitrosative stress in ischemia-induced autophagy-lysosome cascades is further supported by our finding that pharmacological inhibition of nitrosative stress by melatonin partially inhibits the ischemia-induced autophagy-lysosome cascade and the degradation of the tight junction proteins. Taken together, the present results demonstrate that peroxynitrite-mediated nitrosative stress at least partially potentiates autophagy-lysosome signaling during sustained ischemic insult-induced endothelial cell damage.

Do probiotics help prevent ventilator-associated pneumonia in critically ill patients? A systematic review with meta-analysis.

BACKGROUND: Probiotic treatments might contribute to the prevention of ventilator-associated pneumonia (VAP). Due to its unclear clinical effects, here we intend to assess the preventive effect and safety of probiotics on intensive care unit (ICU) patients. METHODS: Eligible randomised controlled trials were selected in databases until 30 September 2019. The characteristics of the studies were extracted, including study design, definition of VAP, probiotics intervention, category of included patients, incidence of VAP, mortality, duration of mechanical ventilation (MV) and ICU stay. Heterogeneity was evaluated by Chi-squared and I2 tests. RESULTS: 15 studies involving 2039 patients were identified for analysis. The pooled analysis suggests significant reduction on VAP (risk ratio, 0.68; 95% Cl, 0.60 to 0.77; p<0.00001) in a fixed-effects model. Subgroup analyses performed on the category of clinical and microbiological criteria both support the above conclusion; however, there were no significant differences in duration of MV or length of ICU stay in a random-effects model. Also, no significant differences in total mortality, overall mortality, 28-day mortality or 90-day mortality were found in the fixed-effects model. CONCLUSIONS: The probiotics helped to prevent VAP without impacting the duration of MV, length of ICU stay or mortality.

[An analysis of the survey data on Hangzhou community physicians' perceptions of asthma knowledge and management].

OBJECTIVE: To evaluate the basic knowledge of asthma, the standardization of treatment and the continuing education with community physicians in Hangzhou. METHODS: The survey investigated a total of 45 community health service centers in Hangzhou, and 2 - 4 western medicine physicians were randomly selected from each centre. A questionnaire was completed by totally 114 doctors under investigation. RESULTS: Eighty-seven percent of the physicians believed asthma was an airway inflammatory disease. Sixty-nine percent chose inhaled glucocorticoids as daily first-line drug for persistent asthma and 55% had read asthma guidelines. However, only 24% had ever heard China Asthma Alliance (CAA) and only 6% had visited its website. Moreover, no one under investigation had participated in the CAA organized talks popularizing the standardization of asthma treatment. Over the past year, 55% of the respondents did not participate in any asthma-related meetings or seminars. Ninety-six percent of those surveyed expressed the hope that higher-level hospital doctors would come to the community hospital for asthma-related seminars. Among the 45 community health service centers, only 2 collected part of the registration data for asthma patients and only one conducted health education seminars for asthma patients during the past year. CONCLUSION: Community physicians need to be provided more continuing education opportunities in order for them to provide standard asthma treatment for patients.

Encephalitis caused by Listeria monocytogenes in a healthy adult male in China: A case report.

RATIONALE: Listeria monocytogenes rarely affects immunocompetent adults, and only a few cases of encephalitis caused by L monocytogenes in humans have been reported in China. PATIENT CONCERNS: A 37-year-old male patient presented with headache and fever of 38°C to 39°C for 2 days and dysphoria and dystrophy for 1 day. DIAGNOSIS: The patient was diagnosed as having encephalitis, and his cerebrospinal fluid (CSF) and blood cultures tested positive for L monocytogenes. INTERVENTIONS: The patient was treated with intravenous vancomycin, meropenem, mannitol, methylprednisolone, and enteral nutrition. The computed tomography (CT) scan showed swelling of the brain and hydrocephalus. The patient was treated with emergent surgery, a ventricular drainage tube was inserted, and the CSF was drained daily. OUTCOMES: Despite adequate therapy, the illness was severe and progressed rapidly. The patient died 2 weeks after admission. LESSONS: We report a rare case of L monocytogenes encephalitis in a previously healthy immunocompetent adult in China. The patient's CT scans showed increasing brain swelling and hydrocephalus, and the patient's condition progressively deteriorated.

The value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure.

OBJECTIVE: To investigate the value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure. METHODS: A single-center, prospective, randomized, controlled pilot trial was conducted between January 2013 and December 2014. Sixty enrolled patients were randomized immediately after extubation into either a high-flow nasal cannula group (n=30) or an air entrainment mask group (n=30) at a fixed inspired oxygen fraction (40%). The success rate of oxygen therapy, respiratory and hemodynamic parameters and subjective discomfort (using a visual analogue scale) were assessed at 24h after extubation. RESULTS: The two groups were comparable at extubation. A total of 46 patients were successfully treated including 27 patients in the high-flow nasal cannula group and 19 patients in the air entrainment mask group. Compared to the air entrainment mask group, the success rate of oxygen therapy and the partial pressure of arterial oxygen were significantly higher and the respiratory rate was lower in the high-flow nasal cannula group. In addition, less discomfort related to interface displacement and airway dryness was observed in the high-flow nasal cannula group than in the air entrainment mask group. CONCLUSIONS: At a fixed inspired oxygen fraction, the application of a high-flow nasal cannula after extubation achieves a higher success rate of oxygen therapy and less discomfort at 24h than an air entrainment mask in patients with acute respiratory failure.

Melatonin Attenuates Pain Hypersensitivity and Decreases Astrocyte-Mediated Spinal Neuroinflammation in a Rat Model of Oxaliplatin-Induced Pain.

Neuroinflammatory response in spinal dorsal horn has been demonstrated to be a critical factor in oxaliplatin-induced pain. Melatonin has been shown to have anti-inflammatory and anti-allodynia effects in both preclinical and clinical studies. In the present study, we investigated the role of systemic administration of melatonin on oxaliplatin-induced pain. Intraperitoneal (i.p.) injection with oxaliplatin induced significantly mechanical allodynia and thermal hyperalgesia. Melatonin (i.p.) significantly alleviated mechanical allodynia and thermal hyperalgesia in the oxaliplatin but not sham-treated rats. The attenuation of nociceptive response persisted at least to 3 days after melatonin injection, throughout the entire observing window. Immunohistochemistry showed that oxaliplatin induced a significant increase of glial fibrillary acidic protein (GFAP) immunodensities, which could be suppressed by melatonin. Western blotting showed that GFAP protein levels were significantly elevated in the oxaliplatin-vehicle group. Melatonin significantly decreased oxaliplatin-induced upregulation of GFAP expressions. Oxaliplatin injection also enhanced the messenger RNA (mRNA) expressions of cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and chemokines including monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1 (MIP-1α) in the spinal dorsal horn, which could be significantly repressed by melatonin. In vitro study showed that mRNA levels of TNF-α, IL-1ß, MCP-1, and MIP-1α in primarily astrocytes were significantly increased after lipopolysaccharide (LPS, 1 µg/ml) stimulation. Melatonin (10 and 100 µM) greatly inhibited synthesis of these inflammatory mediators, in a dose-related manner. Conclusively, our data provide a novel implication of anti-nociceptive mechanism of melatonin in chemotherapy-related pain.

[The preventive effect of bacillus Calmette-Guerin vaccination in early life on airway inflammation and mucus production in a murine model of asthma].

OBJECTIVE: To investigate the preventive effect of bacillus Calmette-Guerin (BCG) vaccination in early life on airway inflammation and mucus production in a murine model of asthma. METHODS: Twenty-five newborn C57BL/6 mice were divided into three groups including group A (saline sensitized/challenged mice, n = 8), group B [ovalbumin (OVA) sensitized/challenged mice, n = 9], group C (OVA sensitized/challenged mice treated by BCG in early life, n = 8). Mice in group C were subcutaneously injected by 25 microl BCG (10(3) CFU) four times at 0 week, 1st week, 2nd week and 3rd week of age respectively, while mice in group A and B were injected by the same volume of saline solution. Mice were sensitized on day 42 and 56 by saline (group A) or OVA (group B and C) and challenged from day 66 to 68 by saline (group A) or OVA (group B and C) repeatedly. Samples were collected at 48 h after the last OVA challenge. The outcome measurements included eosinophil count in bronchoalveolar lavage fluid (BALF), periodic acid-schiff reaction (PAS) staining of lung tissues, the goblet cell hyperplasia ratio (HR) and the epithelial cell mucus occupying ratio (MOR). The mRNA expression of mucus gene (MUC5AC) was measured by reverse trancription-polymerase chain reaction (RT-PCR). RESULTS: The total cells in BALF in group B (123.8 +/- 14.5) x 10(4)/ml] and that in group C [(77.4 +/- 14.1) x 10(4)/ml] were increased significantly as compared with that in group A [(15.0 +/- 1.4) x 10(4)/ml, P < 0.01, P < 0.01], but there was no significant difference between group B and group C (P > 0.05). The number of eosinophils in BALF in group B [(78.220 +/- 11.770) x 10(4)/ml] and that in group C [(24.430 +/- 7.020) x 10(4)/ml] were increased significantly when compared with that in group A [(0.090 +/- 0.020) x 10(4)/ml, P < 0.01, P < 0.05], and that in group C was significantly reduced when compared with that in group B (P < 0.01). The HR and MOR in group B [(41.80 +/- 4.09)/mm, (28.43 +/- 2.75)% respectively] and those in group C [(21.58 +/- 5.09)/mm, (9.43 +/- 2.30)% respectively] were increased significantly when compared with those in group A [(3.00 +/- 1.20)/mm, (0.75 +/- 0.29)% respectively, P < 0.01, P < 0.01], but those in group C were significantly reduced when compared with those in group B (P < 0.01). The mRNA expression of MUC5AC in group B (1.07 +/- 0.03) and that in group C (0.86 +/- 0.05) were increased significantly when compared with that in group A (0.64 +/- 0.08, P < 0.01, P < 0.01), but that in group C were significantly reduced when compared with that in group B (P < 0.01). CONCLUSION: BCG vaccination in early life can inhibit the development of airway inflammation and mucus production in a murine model of asthma.

Effect of 5- AZn-2 '-deoxycytidine on proliferation of human lung adenocarcinoma cell line A549 in vitro.

OBJECTIVE: To explore effect of 5-AZn-2 '-deoxycytidine on proliferation of human lung adenocarcinoma cell line A549 in vitro. METHODS: Superoxide dismutase (SOD) activity was measured by hydroxylamine colorimetric method. Inhibition effect of 5-AZn-2' deoxycytidylic acid at different concentration and different time on growth of A549 cell was determined by MTT assay. Methylene dioxyamphetamine (MDA) was measured by thiobarbituric acid colorimetric method. Effect of 5-AZn-2' deoxycytidylic acid on apoptosis of A549 cell was determined by Hoechst 33258 dyeing detection. RESULTS: 5-AZn-2' deoxycytidylic acid had significant inhibition effect on proliferation of A549 cells in vitro, and the inhibition was notably dependent on time and dosage during 48-72 h; SOD level was significantly lower than those of control group (P<0.05, P<0.01), MDA level was significantly higher than those in the control group (P<0.05, P<0.01). A549 cells began to be in apoptosis after using 5-AZn-2'deoxycytidylic acid. CONCLUSIONS: 5- AZn-2' deoxycytidylic acid has significant inhibition effect on growth of A549 cell, and can lead the change of lipid peroxidation. It indicates that the mechanism has relationship with A549 cell cycle tissue and induction factor of apoptosis.

The γ-secretase blocker DAPT reduces the permeability of the blood-brain barrier by decreasing the ubiquitination and degradation of occludin during permanent brain ischemia.

BACKGROUND: Tight junction protein degradation is a principal characteristic of the blood-brain barrier (BBB) damage that occurs during brain ischemia. AIMS: We investigated the mechanisms of occludin degradation that underlie permanent middle cerebral artery occlusion (pMCAO) in rats. METHODS AND RESULTS: Western blot and Co-immunoprecipitation data indicated ubiquitination and degradation of occludin in brain after pMCAO, which was consistent with ZO-1 degradation in penumbra regions as observed at 24 h after pMCAO. We further investigated candidate protease(s) responsible for the degradation of occludin during pMCAO. The intraventricular administration of γ-secretase blocker DAPT significantly inhibited the pMCAO-induced neurovascular damage, whereas ALLM and Batimastat, which are inhibitors of calpain and metalloproteinase proteases, respectively, were less effective. Notably, we found that DAPT significantly inhibited BBB disruption in comparison with vehicle treatment, as assessed by Evans blue excretion. Interestingly, the confocal immunostaining revealed that activation of the E3 ubiquitin ligase Itch is associated with degradation of occludin in brain microvessels following ischemia. Furthermore, our data demonstrate that the inhibition of γ-secretase signaling and the itch-mediated ubiquitination of occludin likely underlie the vasoprotective effect of DAPT after pMCAO. CONCLUSION: The γ-secretase blocker DAPT reduces the permeability of the BBB by decreasing the ubiquitination and degradation of occludin during permanent brain ischemia, suggesting that γ-secretase may represent a novel therapeutic target for preventing neurovascular damage.

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

BACKGROUND: Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes. AIMS: To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats. METHODS: Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry. RESULTS: Our data showed a pronounced decrease in the phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type 1 and type 2 diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I (Ser 603) and GluR1 (Ser 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP1α and PP2A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up-regulated in type 2 diabetic rats. CONCLUSIONS: The disturbance of CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.

The value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure

OBJECTIVE: To investigate the value of high-flow nasal cannula oxygen therapy after extubation in patients with acute respiratory failure. METHODS: A single-center, prospective, randomized, controlled pilot trial was conducted between January 2013 and December 2014. Sixty enrolled patients were randomized immediately after extubation into either a high-flow nasal cannula group (n=30) or an air entrainment mask group (n=30) at a fixed inspired oxygen fraction (40%). The success rate of oxygen therapy, respiratory and hemodynamic parameters and subjective discomfort (using a visual analogue scale) were assessed at 24h after extubation. RESULTS: The two groups were comparable at extubation. A total of 46 patients were successfully treated including 27 patients in the high-flow nasal cannula group and 19 patients in the air entrainment mask group. Compared to the air entrainment mask group, the success rate of oxygen therapy and the partial pressure of arterial oxygen were significantly higher and the respiratory rate was lower in the high-flow nasal cannula group. In addition, less discomfort related to interface displacement and airway dryness was observed in the high-flow nasal cannula group than in the air entrainment mask group. CONCLUSIONS: At a fixed inspired oxygen fraction, the application of a high-flow nasal cannula after extubation achieves a higher success rate of oxygen therapy and less discomfort at 24h than an air entrainment mask in patients with acute respiratory failure.

Expression profiling of Ca(2+)/calmodulin-dependent signaling molecules in the rat dorsal and ventral hippocampus after acute lead exposure.

The septal and temporal poles of the hippocampus differ markedly in their anatomical organization, but whether these distinct regions exhibit differential neurochemical profiles underlying lead (Pb(2+)) neurotoxicity remains to be determined. In the present study, we examined changes in the expression of Ca(2+)/calmodulin-dependent enzymes, including calpain, calcineurin, phospho-CaMKII (Thr286) and neuronal nitric oxide synthase (nNOS), in the rat dorsal and ventral hippocampus (DH and VH) after acute Pb(2+) exposure. Five days after Pb(2+) exposure, we observed constitutively active forms of calcineurin (45 kDa and 48 kDa) in ventral portions of the hippocampus, a result consistent with the observed calpain activation that is indicated by the breakdown of spectrin in this region. Our data demonstrate that nNOS expression is significantly higher in the ventral region of the hippocampus when compared to the dorsal region, whereas phosphorylation of CaMKII (Thr286) is less pronounced in the ventral portion of the hippocampus and more pronounced in dorsal regions after acute Pb(2+) exposure. Thus, it appears likely that the ventral region of hippocampus is more vulnerable to the neurotoxic effects of Pb(2+) than the dorsal region. Taken together, the present data suggest that acute lead exposure leads to differential expression patterns of Ca(2+)/calmodulin-dependent enzymes along the dorsoventral axis of the hippocampus.