Objective To investigate the effects of propofol on the spontanous rhythmical respiratory discharges (SRRDs) in the isolated medulla spinal cord preparation of newborn rats and its possible mechanism Methods Newborn SD rats (0 3 days) of either sex were used Isolated medulla spinal cord preparation was made according to the method of Suzue, et al Brain stem was severed between medulla and pons and spinal cord was severed between cervical and thoracic segments Efforts were made to keep the ventral root of the cervical spinal nerves of possible, while the medulla spinal cord preparation was being removed The medulla spinal cord preparation was placed with the ventral side facing up in the bath continuously perfused with modified Krebs solution (MKS)(3 4ml/min,T=27℃, pH=7 3 7 4, 95% O 2 5% CO 2) glass adsorb electrodes containing Ag AgCl needle were attached to the rentral root of C 4 or C 5 spinal nerve SRRD were recorded, Forty eitht isolated medulla spinal cord preparations were divided into 7 groups: groupⅠ: control group in which preparation was perfused with MKS only; groupⅡ Ⅳ: propofol groups in which preparation was perfused continuously for 3 min with different concentrations of propofol (5, 20, 50, 100, 250 ?mol/L); group Ⅶ: bicuculine propofol group in which preparation was continuously perfuse for 3min with a specific GABAA receptor blocker, bicuculine (20?mol/L) followed by perfusion of propofol(20?mol/L) for another 3 min SRRDs were recorded before and 1, 3, 5, 10, 15, and 30 min after propofol or bicuculine propofol perfusion Results 1) In control group, there was no significant change in SRRDs at the designated time internals 2) In group Ⅱ Ⅵ after propofol perfusion, the bursts of SRRDs were inhibited in a concentration dependent manner, but at 1 3 min SRRD showed a temporary excitation (frequency increased and expiratory time became shorter), at 5 min frequency began to slow down and expiratory time became prolonged, at 15 min in 7 out of preparations were stopped in group Ⅵ (propofol 250 ?mol/L) Inspiratory time did not change significantly after propofol in all propofol groups, but integral area of discharge (IAD) of SRRD showed some enlargement until SRRDs stopped 3) with bicuculine(20 ?mol/L) pretreatment, SRRDs did not change significantly after perfusion with propofol (20 ?mol/L) Conclusions Propofol inhibits SRRDs in a conecntration dependent manner as shown by prolongation of expiratory time GABAA receptor may play an important role in inhibitory action of propofol on the isolated medulla spinal cord preparation from newborn rats

Objective To investigate the effects of sufentanil,remifentanil and fentanyl oH cellular immune function in patients undergoing radical resection of esophageal cancer.Methods Forty-five ASA Ⅰ or Ⅱpatients aged 45-64 yr undergoing radical resection of esophageal cancer were randomly divided into 3 groups(n=15 each):sufentanil group(SF);remifentanil group(RF)and fentanyl group(F).The patients were premedicated with iv atropine 0.5 mg.Anesthesia was induced with midazolam 0.04 mg/kg,propofol TCI(CT=3μg/ml)and TCI of sufentanil,remifentanil or fentanyl(CT=0.5,5 and 5 ng,ml respectively in the 3 groups).Endobronchial intubation was facilitated with vecuronium 0.1 mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 30-40 mm Hg.Anesthesia was maintained with inhalation of sevoflurane(0.7-1.5 MAC)and TCI of sufentanil,remifentanil or fentanyl(CT=0.5,5 and 5 ng/ml respectively).Venous blood samples were taken from peripheral vein before anesthesia(T0,baseline),60 min after skin incision(T1),immediately(T2),24 h(T3)and 72 h(T4)after the end of operation for determination of the expression of CD3+,CIM+,CD8+on T cells and CD3-CD16+CD56+on natural killer cells by flow cytometry,CD4+/CD8+ratio,serum concentrations of IL-2 and IL-10 by ELISA.Results Compared with the baseline values,the CD4+T-lymphocytes and CIM+/CD8+ratio were significantly decreased at T2,while the CD3-CD16+CD56+NK cells were significantly increased in all 3 groups.The CD3+T-lymphocytes were significantly decreased at T2 as compared to the baseline value at T0 in SF and RF groups.The CIM+and CD3+T-lymphocytes were significantly decreased at T3 as compared with the baseline value in all 3 groups.Serum IL-2 concentration was significantly higher at T3 in SF group than in RF group.Serum IL-10 concentration was sismficantly higher at T4 in RF group than in SF group.Conclusion Sufentanil,remifentanil and fentanyl can depress cenular immune function to some extent in patients undergoing radical resection of esophageal cancer.

HuR (human antigen R), an mRNA-binding protein responsible for poor prognosis in nearly all kinds of malignancies, is a potential anti-tumor target for drug development. While screening HuR inhibitors with a fluorescence polarization (FP) based high-throughput screening (HTS) system, the clinically used drug eltrombopag was identified. Activity of eltrombopag on molecular level was verified with FP, electrophoretic mobility shift assay (EMSA), simulation docking and surface plasmon resonance (SPR). Further, we showed that eltrombopag inhibited cell proliferation of multiple cancer cell lines and macrophages, and the anti-tumor activity was also demonstrated in a 4T1 tumor-bearing mouse model. The data showed that eltrombopag was efficient in reducing microvessels in tumor tissues. We then confirmed the HuR-dependent anti-angiogenesis effect of eltrombopag in 4T1 cells and RAW264.7 macrophages with qRT-PCR, HuR-overexpression and HuR-silencing assays, RNA stability assays, RNA immunoprecipitation and luciferase assays. Finally, we analyzed the anti-angiogenesis effect of eltrombopag on human umbilical vein endothelial cells (HUVECs) mediated by macrophages with cell scratch assay and Matrigel angiogenesis assay. With these data, we revealed the HuR-dependent anti-angiogenesis effect of eltrombopag in breast tumor, suggesting that the existing drug eltrombopag may be used as an anti-cancer drug.