Design, synthesis and biological evaluation of indole derivatives as novel cholesteryl ester transfer protein inhibitors
Chinese Journal of Medicinal Chemistry,Vol 28,No. 02
CETP facilitates the movement of cholesteryl esters (CEs) from HDL to LDL and VLDL, which leads to lower levels of HDL-C. So developing high efficient and low side effect CETP inhibitors will be another strategy in treatment of atherosclerotic cardiovascular disease. According to our previous study, we used compound Ⅰ as a lead compound for further optimization. Structure optimization was divided into two parts: Firstly, replacing the H atom by different substituent groups at the 5-position and 1-position. Furthermore, we moved the side chain from the 2-position to 3-position and modified the 1 and 2-positions of indole. Compounds 10a– 10h were obtained via reduction, oxidation, reductive amination, substitution, Suzuki coupling reaction and nucleophilic substitution, using indol-2-carboxylic acid ethyl ester derivatives as starting material. Based on indole or ethyl indole-2-carboxylate, the formal group was introduced by Vilsmeier reaction. The aldehyde intermediates underwent reductive amination, substitution, Suzuki coupling reaction and nucleophilic substitution to provide compounds 15a– 15g. The other two compounds ( 15h, 15i) were obtained from compound 15c. Seventeen compounds were obtained and all of the compounds have not been reported in literatures and their structures w ere confirmed by 1H-NMR, 13C-NMR and MS. Utilizing the BODIPY-CE fluorometry, we obtained the in vitro activities of compounds. The results showed that compound 10h had good inhibitory activity against CETP.
Effect of two-step approach combined with unprotected perineum method on the incidence of swallowing syndrome in neonates
Chinese Journal of Nursing,Vol 53,No. 02
Objective To evaluate the effect of two-step approach combined with unprotected perineum method on the incidence of neonatal swallowing syndrome. Methods A total of 360 patients were randomly divided into three groups: A, B and C, with 120 cases in each group. Traditional midwifery approach was adopted for group A: midwife manually controlled the delivery rate of fetal head with hands, assisted in delivering fetal shoulders after fetal head was delivered, quickly used hands to clean up the completely-delivered neonate and routinely sucked mucus from mouth and nose using aurilave. Two-step approach combined with unprotected perineum method was adopted for groups B and C: midwife did not interfere delivery with hands, and parturition was paused after the fetal head was delivered; the fetal shoulders were delivered until next contraction. Respiratory tracts of group B was cleaned up like group A and group C was only provided surface cleaning or squeezing nose and mouth using hands. The incidences of neonatal swallowing syndrome and vomiting times in the three groups were recorded within 24 h after birth, and the difference among three groups was compared. Results The incidence of neonatal swallowing syndrome in group A was higher than those in groups B ( χ2 = 6.504, P = 0.011) and C ( χ2 = 7.533, P = 0.006); there was no significant difference between group A and B in neonatal swallowing syndrome ( χ2 = 0.042, P = 0.837). There were significant difference in vomiting times within 24 h among three groups ( F = 10.185, P = 0.006). There was significant difference in vomiting times within 24 h between group A and group B, and between group A and group C ( P < 0.05); there was no significant difference between group B and group C ( P > 0.05). Conclusion Implementing the two-step approach combined with unprotected perineum method, the neonates can accomplish cleaning up respiratory tract naturally during natural delivery of fetal shoulders.
Electroacupuncture Stimulation of Different Acupoint or Paired Acupoints on Expression of BDNF and TrkB Proteins and Genes in Hippocampus in Myocardial Ischemic Rats
Acupuncture Research,Vol 41,No. 01
Objective To observe the protective effect of electroacupuncture (EA) intervention on the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) proteins and genes in the hippocampus areas in myocardial ischemia (MI) rats, so as to reveal its underlying mechanisms in protecting hippocampal cells under MI. Methods Eighty healthy male SD rats were randomized into sham-operation, MI model, Shenmen (HT 7), HT 7-Zhizheng (SI 7) and HT 7-Xinshu (BL 15) groups ( n = 15 in each group). The MI model was established by occlusion of the anterior descending branch of the left coronary artery. EA (2 Hz, 2 mA) was applied to bilateral HT 7, HT 7–SI 7, and HT 7–BL 15, respectively for 15 min, once per day for a week. The number of BDNF and its receptor TrkB positive cells in the left hippocampus and that of mRNAs in the right hippocampal tissue were determined by immunohistochemistry and real-time fluorescence quantitative PCR, respectively. Results In comparison with the sham group, the numbers of both BDNF and TrkB positive cells in the left hippocampus and the expression levels of BDNF mRNA and TrkB mRNA in the right hippocampus were increased slightly ( P > 0.05). After EA intervention, the numbers of hippocampal BDNF and TrkB positive cells and the expression levels of BDNF mRNA and TrkB mRNA were evidently up-regulated ( P < 0.05, P < 0.01), and the effects of HT 7–SI 7 and HT 7–BL 15 were obviously superior to those of simple HT 7 in up-regulating BDNF and TrkB expression ( P < 0.01, P < 0.05). No significant differences was found between the HT 7-SI 7 and HT 7-BL 15 groups in increasing the number of hippocampal BDNF and TrkB positive cells and in up-regulating expression of both BDNF mRNA and TrkB mRNA ( P > 0.05). Conclusion EA intervention is effective in increasing the expression of hippocampal BDNF and TrkB in MI rats, which may contribute to its efficacy in protecting hippocampal cells from injury under MI condition. The effect of EA stimulation of HT 7–SI 7 and HT 7–BL 15 was obviously superior to that of simple HT 7 in up-regulating BDNF and TrkB expression.
Chinese Journal of Lasers,Vol 43,No. 07
A GHz narrow-linewidth high-peak power nanosecond fiber laser based on the master oscillator power amplifier (MOPA) is reported. The modulated distributed feedback single-frequency diode laser seed delivers pulses with wavelength of 1 064.12 nm, pulse width of 3.92 ns, and tunable repetition rate from 10 kHz to 50 kHz. A double-pass structure is used in the preamplifier to boost small signal and suppress amplification of spontaneous emission under intense pump. In the power amplifier, the stimulated Brillouin scattering is avoided by shortening fiber length. Pulsed laser with 1.5 GHz linewidth and 15 kW peak power is obtained at a repetition rate of 10 kHz. The output pulse characteristics at different repetition rates are studied.
Preparation and Cryogenic Properties of Cyanate Ester Resin Blends Co-modified by Phenoxy Resin/Epoxy Resin
Journal of Aeronautical Materials,Vol 38,No. 03
The modified cyanate ester resin (CE) which can be applied stably in the cryogenic environment was prepared by using phenoxy resin (PKHH) and high purity epoxy resin (EP) through the method of melting prepolymerization. The results show that the curing reaction of CE is accelerated by the addition of PKHH, but the reaction pathways are not changed. It is found that PKHH can improve the ductility by the mechanism of the semi-interpenetrating network (SIPN) in the cured CE networks. Especially, the impact strength value of the CE/EP blends with the content of 10% (mass fraction) PKHH reaches to 18.4 kJ/m 2 and the modulus is maintained at about 3.5 GPa at −196 °C. The cracks are not observed on the surface of specimens after 14 low–high temperature cycles (−196 to 200 °C).