miR-141 exacerbates lung ischemia-reperfusion injury by targeting EGFR/ß-catenin axis-mediated autophagy.

Some microRNAs (miRNAs) play important roles in lung ischemia-reperfusion injury (LIRI) injury. Here, this study aimed to examine whether miR-141 was related to lung ischemia-reperfusion injury (IRI) via regulating autophagy and the epidermal growth factor receptor (EGFR), and to explore the underlying signal transduction pathways. To this end, we constructed the LIRI cell model and mouse models, separately. According to RT-qPCR and Western blotting (WB) analysis results, miR-141 up-regulation together with ß-catenin and EGFR down-regulation within mouse pulmonary microvascular endothelial cells (PMVECs) or lung tissues was related to lung IRI. Besides, we conducted dual-luciferase reporter assay, which suggested the binding of EGFR to miR-141. In addition, we carried out TUNEL staining, HE staining, and flow cytometric analysis to assess the apoptosis of PMVECs and the injury to mouse lung tissues. Furthermore, we performed light-chain immunofluorescence assay to examine autophagosomes within PMVECs. According to our results, miR-141 suppressed ß-catenin level through reducing EGFR level. Besides, the miR-141/EGFR/ß-catenin axis enhanced autophagy to aggravate LIRI. To sum up, miR-141 suppresses EGFR expression to inhibit ß-catenin level, which subsequently aggravates autophagy and complicates LIRI. The above results offer the candidate therapeutic target for the treatment of lung IRI.

Antimicrobial Coating: Tracheal Tube Application.

Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection in mechanically ventilated patients, increasing mortality, prolonging the patient length of stay, and increasing costs. In recent years, extensive studies on ventilator-associated pneumonia have shown that tracheal intubation plays an essential role in the pathogenesis of VAP, with the primary mechanism being the rapid colonization of the tracheal intubation surface by microbiota. Antibiotics do not combat microbial airway colonization, and antimicrobial coating materials offer new ideas to solve this problem. This paper reviews the current research progress on the role of endotracheal tube (ET) biofilms in the pathogenesis of VAP and antimicrobial coating materials.

Bovine Milk Exosomes Alleviate Cardiac Fibrosis via Enhancing Angiogenesis In Vivo and In Vitro.

Cardiac fibrosis is a difficult clinical puzzle without effective therapy. Exosomes play an important role in alleviating cardiac fibrosis via angiogenesis. This research aimed to assess the effect of bovine milk on cardiac fibrosis. The proangiogenic effect of bovine milk exosomes was analyzed both in isoproterenol (ISO)-induced cardiac fibrosis rats in vivo and in human umbilical vein endothelial cells (HUVECs) after oxygen and glucose deprivation (OGD) in vitro. Results indicated that bovine milk exosomes alleviated the extracellular matrix (ECM) deposition and enhanced the cardiac function in cardiac fibrosis rat. The proangiogenic growth factors were significantly enhanced in rats accepted bovine milk exosomes. Meanwhile, bovine milk exosomes ameliorated the motility, migration, and tube-forming ability of HUVECs after OGD in vitro. Bovine milk exosomes alleviate cardiac fibrosis and enhance cardiac function in cardiac fibrosis rats via enhancing angiogenesis. Bovine milk exosomes may represent a potential strategy for the treatment of cardiac fibrosis.

Safety and Efficacy of a Novel Intubating Laryngeal Mask during the recovery period following Supratentorial Tumour Surgery.

OBJECTIVE: To assess safety and efficacy of a novel intubation laryngeal mask airway (ILMA) during the recovery period following supratentorial tumour surgery. METHODS: Patients who underwent supratentorial tumour surgery at our centre from January 2012 to December 2016 were eligible for this prospective randomised, parallel group study. We developed a novel ILMA using closely fitting laryngeal masks (No. 4/5) with 7.0/7.5 mm endotracheal tubes (ETT) plus screw fixators and anti-pollution sleeves. RESULTS: In total, 100 patients were intubated with the novel ILMA and 100 the ETT. There were no differences between groups in haemodynamic variables, oxygen saturation, exhaled CO2, or bispectral index all recorded during the 72-hour recovery period. However, there were significantly fewer incidences of coughing, less fluid drainage and lower haemoglobin levels in surgical fluid in the ILMA group compared with the ETT group. CONCLUSION: Our novel ILMA device was associated with reduced coughing, fluid drainage and blood in surgical drain during the recovery period following supratentorial tumour surgery.

Correlation between controlled lung collapse and early lung injury in dogs.

A new type of pulmonary sequestration ventilator was used to compare the relationship between controlled lung collapse and early lung injury in thoracic surgery for dogs. Eighteen experimental dogs were randomly divided into three groups (G1-G3 groups). After general anesthesia, the shunt balance in lung was controlled and the pulmonary sequestration tube was placed in the femoral artery and vein, and the Swan-Ganz tube was placed into the right internal jugular vein as well. Two-lung ventilation (TLV) was first performed for 20 min, followed by one-lung ventilation (OLV). The degree of collapse was 100% (G1), 90% (G2), and 50% (G3). Blood samples were extracted from femoral artery and jugular vein prior to collapse (T0), and at 30 (T1), 60 (T2), and 120 (T3) min after collapse for blood gas analysis to determine the shunt ratio (Qs/Qt). Blood samples were also subjected to enzyme linked immunosorbent assay (ELISA) to determine serum tumor necrosis factor-α (TNF-α), intercellular immune adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) levels. Arterial blood pressure, heart rate, pulmonary artery pressure and other physiological indicators were monitored during the experiment. Lung tissues were collected at T3 to calculate the wet/dry weight ratio (W/D). Histopathological changes were observed and compared by microscopic observation and blind scoring of pathological section after hematoxylin and eosin (H&E) staining. There were no significant differences in the physiological indexes between the two groups during TLV (P>0.05). Mean pulmonary arterial pressure (MPAP) in G2 and G3 groups was significantly more stable than that in G1 group after OLV (P<0.05); shunt ratio Qs/Qt, W/D, and serum TNF-α, ICAM-1 and IL-6 levels in the lung were decreased; and the degrees of pulmonary edema, hemorrhage, inflammatory cell infiltration and lung injury were also decreased. There was no statistically significant difference in each index at each time-point between G2 and G3 groups (P>0.05). Compared with complete lung collapse (collapse degree: 100%), controlled lung collapse (collapse degree: 90% and 50%) can better reduce the intraoperative lung injury, but there was no significant difference between the collapse degrees of 90 and 50%.

Effect of Parecoxib as an Adjunct to Patient-Controlled Epidural Analgesia after Abdominal Hysterectomy: A Multicenter, Randomized, Placebo-Controlled Trial.

OBJECTIVE: This multicenter, randomized, placebo-controlled study evaluated the efficacy and side effects of parecoxib during patient-controlled epidural analgesia (PCEA) after abdominal hysterectomy. METHODS: A total of 240 patients who were scheduled for elective abdominal hysterectomy under combined spinal-epidural anesthesia received PCEA plus postoperative intravenous parecoxib 40 mg or saline every 12 h for 48 h after an initial preoperative dose of parecoxib 40 mg or saline. An epidural loading dose of a mixture of 6 mL of 0.25% ropivacaine and 2 mg morphine was administered 30 min before the end of surgery, and PCEA was initiated using 1.25 mg/mL ropivacaine and 0.05 mg/mL morphine with a 2-mL/h background infusion and 2-mL bolus with a 15-min lockout. The primary end point of this study was the quantification of the PCEA-sparing effect of parecoxib. RESULTS: Demographic data were similar between the two groups. Patients in the parecoxib group received significantly fewer self-administrated boluses (0 (0, 3) vs. 7 (2, 15), P < 0.001) and less epidural morphine (5.01 ± 0.44 vs. 5.95 ± 1.29 mg, P < 0.001) but experienced greater pain relief compared with the control group (P < 0.001). Patient global satisfaction was higher in the parecoxib group than the control group (P < 0.001). Length of hospitalization (9.50 ± 2.1, 95% CI 9.12~9.88 vs. 10.41 ± 2.6, 95% CI 9.95~10.87, P = 0.003) and postoperative vomiting (17% vs. 29%, P < 0.05) were also reduced in the parecoxib group. There were no serious adverse effects in either group. CONCLUSION: Our data suggest that adjunctive parecoxib during PCEA following abdominal hysterectomy is safe and efficacious in reducing pain, requirements of epidural analgesics, and side effects. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01566669).

The Effects of Urethane on Rat Outer Hair Cells.

The cochlea converts sound vibration into electrical impulses and amplifies the low-level sound signal. Urethane, a widely used anesthetic in animal research, has been shown to reduce the neural responses to auditory stimuli. However, the effects of urethane on cochlea, especially on the function of outer hair cells, remain largely unknown. In the present study, we compared the cochlear microphonic responses between awake and urethane-anesthetized rats. The results revealed that the amplitude of the cochlear microphonic was decreased by urethane, resulting in an increase in the threshold at all of the sound frequencies examined. To deduce the possible mechanism underlying the urethane-induced decrease in cochlear sensitivity, we examined the electrical response properties of isolated outer hair cells using whole-cell patch-clamp recording. We found that urethane hyperpolarizes the outer hair cell membrane potential in a dose-dependent manner and elicits larger outward current. This urethane-induced outward current was blocked by strychnine, an antagonist of the α9 subunit of the nicotinic acetylcholine receptor. Meanwhile, the function of the outer hair cell motor protein, prestin, was not affected. These results suggest that urethane anesthesia is expected to decrease the responses of outer hair cells, whereas the frequency selectivity of cochlea remains unchanged.

[The effect of dexmedetomidine on autophagy and apoptosis in intestinal ischemia reperfusion-induced lung injury].

OBJECTIVE: To investigate the protective effects of dexmedetomidine against autophagy and apoptosis in intestinal ischemia reperfusion (I/R)-induced lung injury. METHODS: Twenty-four SD rats were randomly and equally divided into 4 groups according to the random number table: control group, I/R group, small dose of dexmedetomidine (D1) group and large dose of dexmedetomidine (D2) group. The model of lung injury was induced by occlusion of the superior mesenteric artery for 60 min followed by 12 h reperfusion. Rats in D1 and D2 groups received intravenous injection of dexmedetomidine at dose of 1 µg/kg and 5 µg/kg respectively. Rats in control and I/R groups were given same volume of normal saline. Pathological changes were detected by hematoxylin-eosin (HE) staining. The microtubule-associated protein 1 light chain 3(LC3)II/I ratio, Beclin-1, Bax and Bcl-2 expression were measured by Western blot. Cell apoptosis was assayed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while caspase-3 activity was evaluated by immunohistochemistry. RESULTS: Significant infiltration of neutrophils and thickened alveolar walls were observed in the I/R group compared to the control group, which were improved by dexmedetomidine (5 µg/kg) treatment. Compared to the control group, the apoptosis cells [(69 ± 8) cells/field], LC3 II/I ratio(57 ± 8), Beclin-1(487%± 45%) and Bax (358% ± 37%) expression were markedly increased (P<0.05), while Bcl-2 (39% ± 5%) expression was decreased (P<0.05) in the I/R group. Compared to the I/R group, the apoptosis cells [(32 ± 5) cells/field], LC3 II/I ratio(27 ± 4), Beclin-1 (285%± 41%) and Bax (181% ± 25%) expression were markedly reduced (P<0.05), while Bcl-2 (91% ± 9%) expression was increased (P<0.05) in the D2 group. CONCLUSIONS: Autophagy and apoptosis were activated in intestinal I/R-induced lung injury. Dexmedetomidine ameliorated intestinal I/R-induced lung injury via reducing autophagy and apoptosis.

[Protective Effect of Ulinastatin against Activation of Tourniquet-Induced Platelet Mitochondria Apoptotic Signaling].

OBJECTIVE: To investigate the protective effect of ulinastatin against the activation of tourniquet-induced platelet mitochondria apoptotic signaling. METHOD: 44 patients with unilateral lower limb operation and tourniquet application were randomly divided into normal saline group and ulinastatin group, and were treated with normal saline and ulinastatin respectively. 12 patents with unilateral lower limb operation but without tourniquet application were enrolled in control group. Lipid hydroperoxide (LPO) in serum was detected by LPO assay kit, the content of ATP was examined by fluorescein-luciferase assay kit; the change of mitochondrial membrane potential (Δ ψm) was detected by JC-1 mitochondrial membrane potential kit; the content of cytoplasmic cytochrome C was examined by Cytochrome C ELISA kit; Caspase-3 activity was detected by Caspase-3 fluorometric assay kit. RESULTS: As compared with control group, the patients in normal saline group exhibited significant platelet mitochondrial dysfunction which characterized by low ATP level and low mitochondrial membrane potential (Δ ψm) (P < 0.05). Tourniquet application resulted in the activation of the mitochondria apoptotic signaling in platelet, displaying increase in the serum LPO level, release of mitochondrial cytochrome C into the cytoplasm, and activation of caspase-3 (P < 0.05). These alterations above-mentioned were obviously improved by ulinastatin treatment (P < 0.05). CONCLUSION: Tourniquet induces platelet mitochondrial dysfunction and mitochondria-dependent apoptotic signaling activation, which can be improved by ulinastatin treatment.

Propofol inhibits lipopolysaccharide-induced tumor necrosis factor-alpha expression and myocardial depression through decreasing the generation of superoxide anion in cardiomyocytes.

TNF-α has been shown to be a major factor responsible for myocardial depression in sepsis. The aim of this study was to investigate the effect of an anesthetic, propofol, on TNF-α expression in cardiomyocytes treated with LPS both in vivo and in vitro. In cultured cardiomyocytes, compared with control group, propofol significantly reduced protein expression of gp91phox and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2) and p38 MAPK, which associates with reduced TNF-α production. In in vivo mice studies, propofol significantly improved myocardial depression and increased survival rate of mice after LPS treatment or during endotoxemia, which associates with reduced myocardial TNF-α production, gp91phox, ERK1/2, and p38 MAPK. It is concluded that propofol abrogates LPS-induced TNF-α production and alleviates cardiac depression through gp91phox/ERK1/2 or p38 MAPK signal pathway. These findings have great clinical importance in the application of propofol for patients enduring sepsis.

Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

BACKGROUND: Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia. METHODS: Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia. RESULTS: Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness. CONCLUSIONS: These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.

The metabolism of trifluoperazine (TFP) exhibits atypical kinetic behavior in both human liver microsomes (HLMs) and monkey liver microsomes (MyLM).

Glucuronidation reaction of trifluoperazine (TFP) is a typical probe reaction to phenotype the activity of UDP-glucuronosyltransferase 1A4. The present study aims to compare the metabolic behavior of TFP in the liver microsomes from human and cynomolgus monkey, including the kinetic type and parameters. In vitro human liver microsome incubation system was used. The Eadie-Hofstee plot was used to determine the kinetic type. The results showed that the data for human liver microsomes (HLMs) and monkey liver microsomes (MyLMs)-catalyzed glucuronidation were best fit to the substrate inhibition model. For the metabolism of TFP in HLMs, the kinetic parameters were calculated to be 40 ± 5 and 140 ± 20 µM for K m and K si values, respectively. For the MyLM-mediated metabolism of TFP, the K m and K si values were calculated to be 108 ± 10 and 250 ± 30 µM, respectively. The same metabolic kinetic type and different kinetic parameters were demonstrated for the metabolism of TFP between HLMs and MyLMs. All these data were helpful for understanding the metabolism difference of TFP between human and monkey.

Propofol inhibits the activation of p38 through up-regulating the expression of annexin A1 to exert its anti-inflammation effect.

Inflammatory response is a kind of nonspecific immune response, with the central link of vascular response, which is mainly manifested by changes in neutrophils and vascular endothelial cells. In recent years, the in vivo and in vitro role of intravenous anesthetic propofol in inhibiting inflammatory response has been attracting more and more attention, but the anti-inflammatory mechanisms of propofol for mononuclear cells still remain undefined. In this study, proteomics analysis was applied to investigate protein expression profile changes in serum mononuclear cells following intervention of rats with endotoxemia using propofol. After two-dimensional electrophoresis and mass spectrometric identification, it has been found that the protein Annexin A1 was up-regulated in the propofol intervention group. Annexin A1 is a glucocorticoid-dependent anti-inflammatory protein. After detection using ELISA and Western blot assays, it has also been found that propofol can not only promote the expression of Annexin A1, but also inhibit the phosphorylation level of p38 and release of inflammatory factors (IL-1ß, IL-6 and TNF-α) in rats with endotoxemia. In order to further determine the role of up-regulated expression of Annexin A1 in anti-inflammation of propofol, this gene was silenced in vitro in human THP-1 cells, to detect the phosphorylation status of p38 and release of inflammatory factors. The results show that Annexin A1 can negatively regulate phosphorylation of p38 and release of IL-1ß, IL-6 and TNF-α in THP-1 cells following propofol intervention and lipopolysaccharide (LPS) stimulation. Our results clearly indicate that propofol can up-regulate Annexin A1 to inhibit the phosphorylation level of p38 and release of IL-1ß, IL-6 and TNF-α, so as to inhibit inflammatory response. Therefore, it can be speculated that Annexin A1 might be the key signaling protein in the in vivo and in vitro anti-inflammatory mechanisms of propofol.

[Effects of parecoxib on morphine dosage in postoperative patient-controlled analgesia following thoracoscope-assisted thoracotomy].

OBJECTIVE: To observe the effect of parecoxib on morphine dosage in patient-controlled analgesia (PCA) following thoracoscope-assisted thoracotomy. METHODS: A consecutive series of 100 patients undergoing thoracoscope-assisted thoracotomy were randomized into 5 groups and received PCA with morphine doses at 0, 5, 10, 15, and 20 mg given in 200 ml saline (groups P(1), P(2), P(3), P(4), and P(5), respectively). Parecoxib (40 mg) was given in all the patients immediately before the operation, and the mixture (4-5 ml) of lidocaine and ropivacaine was administered into the 3 intercostal spaces upper and lower to the incision before chest closure. PCA was administered for each patient. The visual analogue scale (VAS) at rest and coughing and the respiratory functional parameters were recorded at 1, 2, 4, 8, 12, 24, 36, and 48 h after the start of PCA, and the actual and effective button-pressing times (D(1)/D(2)) in PCA were also recorded. RESULTS: No patients showed signs of respiratory inhibition within 24 h after the operation, and the resting VAS was comparable between the groups within the initial 6 postoperative hours. At 8 to 24 h postoperatively, the VAS scores at rest and coughing were significantly higher in P(1) group than in the other groups (P<0.05), and no significant differences were found between the groups at 36 to 48 h. D(1)/D(2) in groups P(1) and P(2) were significantly different from those in the other 3 groups at 4-24 h, but no such difference was found between groups P(3), P(4), and P(5). CONCLUSION: The application of parecoxib may reduce the dosage of morphine in PCA following thoracoscope-assisted thoracotomy and results in good analgesic effect without affecting the patients respiratory function and sputum elimination.

[Effect of propofol on proliferation and differentiation of rat embryonic neural stem cells in vitro].

OBJECTIVE: To investigate the effect of propofol on the proliferation and differentiation of rat embryonic neural stem cells in vitro. METHODS: Embryonic neural stem cells of fetal Wistar rats (gestational age of 14-16 days) in primary culture, after identification for nestin expression, were divided into control group, introlipid group, and propofol groups (treated with propofol at the doses of 5, 25, 50, and 100 µmol/L). The changes in the proliferation of the embryonic neural stem cells after the treatments were observed using Brdu incorporation assay. In the course of induced differentiation of the embryonic neural stem cells, 50 µmol/L propofol was added in the cells to assess its impact on the differentiation of the cells by immunohistochemical detection of NeuN and GFAP expressions. RESULTS: More than 95% of the embryonic neural stem cells in primary culture were Nestin-positive. The percentages of Brdu-positive cells showed no significant changes after treatment with different concentrations of propofol, whereas the addition of 50 µmol/L propofol resulted in a significant increase of NeuN-positive cell percentage to (23.1∓0.9)% as compared with that of (13.4∓0.8)% in the control group (P<0.05) without affecting the GFAP-positive cells. CONCLUSION: Clinically relevant doses of propofol have no obvious effect on the proliferation of rat neural stem cells cultured in vitro, but can induce their differentiation into neuron-like cells.

Rapid UPLC-MS/MS method for the determination of sufentanil in human plasma and its application in target-controlled infusion system.

A rapid, selective and highly sensitive ultra-performance liquid-chromatography mass-spectrometry (UPLC-MS/MS) method has been developed and validated for the determination of sufentanil in human plasma. Sufentanil was separated on an ACQUITY™ UPLC BEH C(18) column (50 mm × 2.1 mm, ID 1.7 µm) and analyzed in positive-ion (PI) electrospray-ionization (ESI) mode. The mobile phase (MP) consisted of acetonitrile:water (45:55, v/v) under isocratic conditions at a flow rate of 0.2 ml/min. Sufentanil and internal-standard (IS) fentanyl were eluted at 1.47 and 1.16 min, respectively, and their responses were optimized at the transitions m/z 387.2>238.0 and m/z 337.2>188.0, respectively. The calibration curve was linear over the range 0.071-4.56 ng/ml, with coefficients of determination >0.999. The accuracy and precision of the method were between 96.49% and 100.37% (RSD<9%), and the mean recovery of sufentanil was 84.08 ± 7.29%. The method was successfully applied to evaluate the predictive accuracy of Gepts pharmacokinetic sets in a target-controlled infusion (TCI) model, and the Gepts parameters were capable of predicting sufentanil plasma concentrations when multi-level target concentrations were acquired during surgery.

Propofol lowers serum PF4 level and partially corrects hypercoagulopathy in endotoxemic rats.

Propofol, an anesthetic drug, has been shown to exhibit antioxidant and anti-inflammatory properties in vitro and in vivo. Hypercoagulopathy is a common clinical feature of sepsis, but the effects of propofol on the coagulation system in septic conditions are unclear. Using the gel-based comparative proteomic approach, together with Western blot analysis, ELISA, antithrombin III activity assay, and blood coagulation test, the effect of propofol on serum proteomic profiles in endotoxemic rats was examined. We identified that serum platelet factor-4 (PF4), an endogenous pro-coagulant, was up-regulated in LPS-challenged rats (p<0.001). Endotoxemia also resulted in hypercoagulopathy as evidenced by the shortening of thromboplastin time and thrombin time. Administration of propofol attenuated LPS-stimulated PF4 release and partially reversed the effect of LPS on thromboplastin time (p=0.0012) and thrombin time (p=0.0072). We demonstrated that propofol reduces serum levels of PF4 and partially corrects the hypercoagulopathy associated with endotoxemia in rats.

The induction of G2/M cell-cycle arrest and apoptosis by cucurbitacin E is associated with increased phosphorylation of eIF2alpha in leukemia cells.

The antiproliferative and apoptotic effects of cucurbitacin E, a natural product isolated from Cucurbitaceae, were determined in human leukemia HL-60 cells. Cucurbitacin E at low concentrations (3-50 nmol/l) inhibited the growth of HL-60 cells, which was associated with G2/M cell-cycle arrest, decrease in the levels of cyclin-dependent kinase1, and increase in the levels of p21. Cucurbitacin E at high concentrations (1-10 mol/l) induced apoptosis of HL-60 cells and activation of caspase-3, caspase-8, and caspase-9. Jurkat leukemia cells with or without caspase-8 expression were nearly equally sensitive to cucurbitacin E-induced apoptosis. Cucurbitacin E did not increase the levels of reactive oxygen species and antioxidants, N-acetylcysteine and catalase, did not block cucurbitacin E-induced apoptosis. Cucurbitacin E decreased the levels of the antiapoptotic proteins XIAP, survivin, and Mcl-1, but increased the level of the proapoptotic protein, Bax. The levels of phosphorylated eukaryotic translation initiation factor 2 subunit (eIF2) were induced in cells undergoing both apoptosis and cell-cycle arrest. As phosphorylated eIF2 is an inhibitor of protein translation initiation, our data suggest that cucurbitacin E induces cell growth arrest and apoptosis through the induction of eIF2 phosphorylation, which leads to the inhibition of cyclin-dependent kinase 1, Mcl-1, survivin, and/or XIAP protein synthesis and that cucurbitacin E induces apoptosis mainly through a mitochondrial-mediated pathway.

[Effect of propofol at different effect-site concentrations on approximate entropy of transient evoked otoacoustic emission signals in adults].

OBJECTIVE: To study the effect of propofol at different effect-site concentrations on approximate entropy (ApEn) of transient evoked otoacoustic emission (TEOAE) signals in adults and investigate the possibility of using ApEn for monitoring anesthesia depth. METHODS: Fifteen ASA class I or II patients (aged 18-49 years with normal hearing) undergoing elective surgery under general anesthesia were enrolled in this study. Anesthesia was maintained with target-controlled infusion of propofol. With the effect-site concentrations of 1, 2, 3 and 4 microg/ml, TEOAE signals were monitored and recorded before and after anesthesia. ApEn of TEOAE in 4 frequency ranges (0-2, 1-3, 2.5-4.5, and 4-6 kHz) were calculated using MATLAB software. RESULTS: The ApEn of TEOAE in different frequency ranges showed no significant differences at the same effect-site concentration of propofol, or at different effect-site concentrations in the same frequency range (P>0.05). CONCLUSION: Anesthesia with propofol at different effect-site concentrations does not obviously affect ApEn of TEOAE signals in adults, and ApEn can not be used as the indicator for evaluating the depth of anesthesia.

[Effects of hypertonic sodium chloride hydroxyethyl starch 40 injection in treatment of acute intracranial hypertension complicated by hemorrhagic shock in dogs].

OBJECTIVE: To observe the effect of hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH) in treatment of acute intracranial hypertension complicated by hemorrhagic shock in dogs, and explore the mechanism of the effects of HSH. METHODS: Twenty dogs were randomized into 4 equal groups, namely the 7.5% NaCl (HS) group, Ringer-Lactates solution (RL) group, hydroxyethyl strarch (HES) group, and HSH group. Canine models of acute intracranial hypertension complicated by hemorrhagic shock were established by epidural balloon inflation with saline and rapid discharge of the arterial blood. One hour after the induced shock, the dogs were given HS (6 ml/kg), RL of 3-fold volume of blood loss, HES of equivalent volume of blood loss, and HSH 8 ml/kg in the 4 groups, respectively. During the shock and resuscitationperiod, the intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) of the dogs were monitored, and the serum sodium level and plasma osmolality were measured at 30 min, 1 h and 4 h after the resuscitation. RESULTS: All dogs had similar MAP, CPP, and ICP before resuscitation (P>0.05). After resuscitation, the MAP was significantly improved (P<0.01), but the dogs in HSH group exhibited the fastest response; with the exception of the dogs in HS group to have significantly decreased MAP 2 h after resuscitation (P<0.01), all the other dogs maintained the MAP for 4 h. The CPP was also significantly increased after resuscitation (P<0.01), and in HS group, CPP decreased significantly after 2 h (P<0.01), and HSH group maintained the high CPP after 4 h. The ICP was increased significantly in RL and HES groups after resuscitation (P<0.01), reaching the peak level at 1 and 3 h, respectively, but in HS and HSH groups, the ICP decreased significantly to the lowest level at 1 h (P<0.01) which was maintained for 4 h. After resuscitation, the plasma sodium and plasma osmolality were significantly increased in HSH and HS groups. CONCLUSION: In dogs with acute intracranial hypertension and hemorrhagic shock, HSH can effectively resuscitate hemorrhagic shock and decrease ICP, and the effect is longer-lasting than that of HS.