BACKGROUND: In clinical, propofol can contract cerebral vessels, decrease cerebral blood flow, decrease brain metabolic oxygen consumption,which can decrease pressure in brain. Studies prove that propofol can protect endothelial cell that may be injuried by active oxygen injury and also decrease nerves injury of experimental rats with cerebral ischemia.OBJECTIVE: To investigate the protective effects of propofol on cerebral ischemia-reperfusion injury in rat and its mechanism.DESIGN: Randomized and controlled study.SETTING:Anesthesiological Department of the Second Affiliated Hospital of Xi'an Jiaotong University.PARTICIPANTS: The experiment was conducted at Pharmacological Laboratory of Medical College of Xi' an Jiaotong University in 2004. Totally 40 healthy male SD rats, aged 3-4 months, weighting 200-300 g, were divided randomly into four groups: Model group, control group, nimodipine group and propofol group, with 10 in each group.METHODS: The rats were anesthetized by intraperitoneal methods with ketamine and propofol separately. When righting reflex was abolished, external carotid artery was separated and ligated. A nylon thread was put at the stump site of external carotid artery without ligation. Model group: 10 mL normal saline was injected into intraperitone in 10 minutes before ischemia.Control group: 10 mL normal saline was injected into intraperitone at the end of operation. Nimodipine group: 10 g/L nimodipine (1 mg/kg) was injected into intraperitone in10 minutes before ischemia. Propofol group: 10 g/L propofol (110 mg/Kg) was injected into intraperitone in 10 minutes before ischemia. When ischemia was lasted for 3 hours, nylon thread was with drawed for reperfusion. When reperfusion was lasted for 3 hours, blood samples were obtained from orbit. Skulls were opened and brains were removed.Effect of propofol on cerebral ischemia-reperfusion injury was observed.MAIN OUTCOME MEASURES: Infarction area, cerebral water content,serum lactate dehydrogenase (LDH) and creatine kinase (CK) levels, brain superoxide dismutase (SOD) activity, malondialdehyde (MDA) and Ca2+levels were measured. Ultrastructure of brain tissue was examined under electron microscope.RESULTS: ①Infarct area in propofol group was significantly smaller than that in model group [(10.45±3.65, 19.68±4.03)%, (t=3.493,P ＜ 0.01)]. ② CK level was lower in propofol group than that in model group [(471±200,1 930±917) IU/L, (t=3.493, P ＜ 0.01)]; and LDH level in propofol group [(8 240±2 580) U/L] was significantly different from that in model group [(15 470±2 680) U/L, (t=3.441, P ＜ 0.01)]; And water content in brain tissue was lower in propofol group than that in model group [(78.2±2.4,82.9±2.9)%, (t=3.321, P ＜ 0.01)]. ③ The death rate of rats was 13.6%in propofol group, and 47.6% in model group, the former was decreased obviously as compared with the latter, and the difference was significant (t=6.21,P ＜ 0.05). ④ SOD activity was (1 690±780) U/g in propofol group and (830±110) U/g in model group, the difference was significant (t=3.420, P ＜ 0.01); but MDA content was obviously lower in propofol group than that in model group [(0.058±0.014, 0.115±0.047) μmol/g, (t=3.336, P ＜ 0.01)].CONCLUSION: Propofol has protective effect on cerebral ischemia-reper fusion injury in rats, and the mechanism is related with inhibition of Ca2+overloading and lipid peroxidation.

Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".

In this study, the buffering capacity of amphiphilic pH-sensitivity copolymer poly(2-ethyl-2-oxazoline)-cholesteryl methyl carbonate (PEOZ-CHMC) was evaluated. The ammonium sulfate gradient method was used to prepare doxorubicin hydrochloride (DOX x HCl)-loaded liposomes (DOX-L), and then the post-insertion method was used to prepare PEOZ-CHMC and polyethylene glycol-distearoyl phosphatidyl ethanolamine (PEG-DSPE) modified DOX x HCl-loaded liposomes (PEOZ-DOX-L and PEG-DOX-L). The physico-chemical properties, in vitro drugs release behavior, cellular toxicity and intracellular delivery of liposomes were evaluated, separately. The results showed that PEOZ-CHMC has a satisfactory buffering capacity. The sephadex G-50 column centrifugation method and dynamic light scattering were used to determine the encapsulation efficiency (EE) and particle size of liposomes. The EE and particle size of DOX-L were (97.3 ± 1.4) % and 120 nm, respectively, and the addition of PEOZ-CHMC or PEG-DSPE had no influence on EE and particle size. The zeta potentials of three kinds of liposomes were negative. The release behavior of various DOX liposomes in vitro was investigated by dialysis method. In phosphate buffer solution (PBS) at pH 7.4, DOX x HCl was released from PEOZ-DOX-L in a sustained manner. While in PBS at pH 5.0, the release rate of DOX x HCl from PEOZ-DOX-L increased significantly, which suggested DOX x HCl was released from PEOZ-DOX-L in a pH-dependent manner. The intracellular delivery of liposomes was investigated by confocal laser scanning microscopy (CLSM). The CLSM images indicated that PEOZ-DOX-L showed efficient intracellular trafficking including endosomal escape and release DOX x HCl into nucleus, as well as the DOX-L and PEG-DOX-L had no this effect. The cytotoxicity of liposomes against MCF-7 cells was detected by using MTT assay. The results showed that antiproliferative effects of PEOZ-DOX-L enhanced with pH value decreased, whereas DOX-L and PEG-DOX-L did not have any significant difference in inhibitions at different pH conditions. Therefore, the problems of the inhibition of cellular uptake of liposomes and the failed endosomal escape of pH-sensitive liposomes by PEG chain can be overcome by the pH-sensitive liposomes constructed by PEOZ-CHMC.

OBJECTIVE: We compared the shear bond strength (SBS) of lingual retainers bonded to bovine enamel with three different resins using direct and indirect methods. METHODS: Both ends of pre-fabricated twisted ligature wires were bonded to bovine enamel surfaces using Light-Core, Tetric N-Flow, or Transbond XT. Phosphoric acid-etched enamel surfaces were primed with One-Step prior to bonding with Light-Core or Tetric N-Flow. Transbond XT primer was used prior to bonding with Transbond XT. After 24 hours in water at 37degrees C, we performed SBS tests on the samples. We also assigned adhesive remnant index (ARI) scores after debonding and predicted the clinical performance of materials and bonding techniques from Weibull analyses. RESULTS: Direct bonding produced significantly higher SBS values than indirect bonding for all materials. The SBS for Light-Core was significantly higher than that for Tetric N-Flow, and there was no significant difference between the direct bonding SBS of Transbond XT and that of Light-Core. Weibull analysis indicated Light-Core performed better than other indirectly bonded resins. CONCLUSIONS: When the SBS of a wire retainer is of primary concern, direct bonding methods are superior to indirect bonding methods. Light-Core may perform better than Transbond XT or Tetric N-Flow when bonded indirectly.
Adhesives ; Composite Resins ; Dental Enamel ; Ligation ; Resin Cements ; Water

Objective To analyze the risk factors of stillbirth in third trimester.Methods Clinical data of 649 cases of stillbirth in third trimester were analyzed retrospectively in 22 hospitals of Haidian district from October 2011 to September 2016, including the incidence, the maternal profile, the perinatal care during pregnancy and the causes of stillbirth.Results (1)The incidence of stillbirth in third trimester in Haidian district from October 2011 to September 2016 was 0.293%(649/221 845).While the incidence in floating pregnant women(0.349%,342/97 939)was higher than that in the residence(0.248%,307/123 906), with statistically significant difference(χ2=19.178,P<0.01).The incidence of stillbirth in multiple pregnancy (0.201%, 89/4 264) was higher than that in singleton pregnancy (0.257%, 560/217 581), with statistically significant difference(χ2=4.690,P<0.01).There was no statistically significant difference in the incidence of stillbirth between male (0.300%, 347/115 632) and female fetuses (0.284%, 302/106 205; χ2=0.467,P>0.05).(2)Among the 649 cases, the floating population accounted for the majority of those who never had prenatal visit (84.0%, 21/25), or less than 5 visits (80.7%, 125/155), or the first visit was beyond 13 gestational weeks(66.0%, 165/649). The causes of stillbirth in order were fetal factors (30.7%, 199/649), maternal factors(28.0%,182/649),umbilical cord factors(20.0%,130/649),unexplained factors(17.6%,114/649) and placental factors (3.7%, 24/649). Birth defects, pregnancy hypertensive disorders, umbilical cord entanglement or torsion were the most important factors, accounting for 22.8%(148/649), 17.4%(113/649), 17.3%(112/649), respectively. Conclusions The floating pregnant women are key population of stillbirth in third trimester.Maternal care and education should be strengthened in this population.The prevention of birth defect, better prenatal care in women with complications, and close monitor during labor are the key measures to reduce the incidence of stillbirth in third trimester.

Objective:To investigate the effects of TNF-α knockout on liver and spleen neutrophil responses to Vibrio vulnificus bloodstream infection in a mouse model. Methods:(1) TNF-α-knockout (TNF-α -/-) and wild-type (WT) C57BL/6J mice aged 6-8 weeks were randomly divided into four groups with six in each group: uninfected WT group, infected WT group, uninfected TNF-α -/- group and infected TNF-α -/- group. The mouse model of bloodstream infection was constructed by intraperitoneal injection of Vibrio vulnificus CGMCC1.1758 (2×10 8 CFU/200 μl), while the mice in the uninfected groups were injected intraperitoneally with equal amount of PBS. (2) Liver immune cells and splenocytes were isolated 4 h after infection and subjected to analyze the percentages and numbers of neutrophils, and the changes in cell viability, cellular reactive oxygen species (ROS) level and phagocytosis by flow cytometry. In addition, effects of Vibrio vulnificus bloodstream infection on mTOR signaling pathway in murine neutrophils were evaluated in vivo. Results:(1)Compared with the uninfected WT group, the percentages and numbers of neutrophils in liver and spleen tissues of the infected WT group increased significantly. The percentage and number of liver neutrophils were significantly higher in the infected TNF-α -/- group than in the infected WT group, but no significant difference in spleen neutrophils was detected between the two groups. (2) Compared with the infected WT group, the phagocytosis of liver neutrophils rather than that of spleen neutrophils was enhanced in the infected TNF-α -/- group. (3) The survival rates of neutrophils in both liver and spleen were decreased, while the cellular ROS level was significantly increased in the infected WT group compared with those of the uninfected WT group. Compared with the infected WT group, the infected TNF-α -/- group had increased survival rates of both liver and spleen neutrophils, but decreased level of ROS. (4) The levels of p-AKT (S473) in liver and spleen neutrophils of the infected WT group were lower than those of the uninfected WT group. Compared with the infected WT group, the infected TNF-α -/- group had lower level of p-AKT (S473) in liver neutrophils, but higher p-AKT (S473) level in spleen neutrophils. There were no significant differences in p-4E-BP1(T37/46) levels between the uninfected WT group and the infected WT group. The p-4E-BP1 (T37/46) level in liver neutrophils was lower in the infected TNF-α -/- group than in the infected WT group, but no significant difference in p-4E-BP1 (T37/46) levels in spleen neutrophils was observed between the two groups. Conclusions:TNF-α had different effects on the neutrophils in spleen and liver tissues of mice with Vibrio vulnificus bloodstream infection. It played a critical role in regulating the recruitment, phagocytic function and mTOR signaling of liver neutrophils after Vibrio vulnificus infection in vivo.