Neprilysin(NEP)is a type Ⅱ integral membrane glycoprotein of the M13 zinc metalloprotease family．As a neuropeptide degrading enzyme,NEP has been discovered to possess an increasing amount of organ-specific functions from central nervous system to peripheral tissues since it was fimfly identified in 1974．For example,NEP has been shown to have an anti-tumour effect by inhibition of cell migration and proliferation while induction of an programmed cell death dependent of both its enzymatic activity and direct protein-protein interactions with key molecules involved in signal transduction pathways:NEP Was also implicated to have neuropmtective effect by preventing the accumulation of the neurotoxic amyloid β-peptide (Aβ)in brain．Through investigating the progression of various human diseases,impaired NEP expression and activity were found to occur frequently．Based on these findings,modulation of NEP levels in pathological cells is considered to be therapeutically applicable as a strategy to recover normal cell functions and thereafter relieve symptoms of diseases．Great research effort is being contributed to the study of regulatory mechanisms involved in expression and activity of this enzyme,and a number of encouraging results have already been achieved．Besides androgens,well-recognised regulators of NEP transcription in prostate,the female hormone oestrogen,aqueous extract of willow herb,components of green tea and neuropeptides bombesin,somatostatin as well as the intracellular domain of amyloid precursor protein were all shown to have a stimulatory effect on NEP expression and／or its activity．

Diversity-oriented synthesis (DOS) aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.
Drug Design ; Drug Discovery ; Small Molecule Libraries

Embryonic Stem Cells ; Humans ; Myocardial Infarction ; therapy ; Stem Cell Transplantation

Arrhythmogenic Right Ventricular Dysplasia ; complications ; Autopsy ; Cardiomyopathy, Hypertrophic ; complications ; Cause of Death ; Coronary Disease ; complications ; Coronary Vessel Anomalies ; complications ; Death, Sudden, Cardiac ; etiology ; pathology ; Humans

0.01). Conclusion: Occlusal reduction might diminish the rate of postoperative pain following endodontic instrumentation.

Objective To investigate the emergency treatment and correlation factors of aqueous misdirection during glaucoma and cataract surgery in glaucoma patients.Design Retrospective case series.Participants 126 cases(132 eyes)of angle-closure glaucoma patients with aqueous misdirection during surgery,100 cases(100 eyes)of angle-closure glaucoma patients without aqueous misdirection during surgery and 100 cases(100 eyes)of senile cataract patients.Methods We performed pars plana vitreous water-bag aspiration or anterior vitrectomy on glaucoma patients with aqueous misdirection during surgery.All the factors in observation group and control groups were compared and analyzed by logistic regression.Main Outcome Measures Preoperative highest intraocular pressure(HIOP),intraocular pressure after maximum dose(IOP),anterior chamber depth(ACD),lens thickness(LENS),axial length (AXL),mean keratometry(K),intraocular lens diopter within-0.5D corrected by SRK-T formula(IOLD).Results Among all the 132 angle-closure glaucoma eyes whose posterior chamber pressures were increased during surgery,we performed pars plana vitreous water-bag aspiration in 123 eyes(93.18%),and anterior vitrectomy in 9 eyes(6.8%).Postoperative complications included shallow anterior chamber in 20 eyes(7 eyes with malignant glaucoma,9 eyes with choroidal detachment,4 eyes with delayed local suprachorodal hemorrhage),and vitreous local hemorrhage in 1 eye.Means of all the observation indexes on three groups showed significant difference(all P

Objective To investigate the direct effects of midazolam on vascular tension and the possible mechanism Methods Male Wistar rats weighing 200 250g were decapitated and the thoraco abdominal sect of aorta was removed and placed in modified Kreb's solution balanced with 95% O 2 and 5% CO 2 After removal of surrounding connective tissue and fat, the aorta was cut into rings 3 4mm in length The endothelium of some of the aorta rings were denuded Aorta rings were suspended in a 37℃ bath of Kreb's solution which was continuously balanced with 95% O 2 and 5% CO 2 One end of the ring was fixed and the other end was connected to a tension monitor through a tension transducer The intactness of endothelium was tested and confirmed by addition of phenylephrine(PE) first and then acetylcholine Aorta rings of each animal were divided into four groups: endothelium intact control group(Ⅰ); endothelium intact experiment group(Ⅱ);endothelium denuded control group(Ⅲ);and endothelium denuded experiment group(Ⅳ) The experiment was carried out in two parts: Part Ⅰ: the effect of midazolam (3?10 -6 ,10?10 -6 ,30?10 -6 ,100?10 -6 mol/L) on endothelium intact and denuded aorta rings which were precontracted with PE(10 -6 mol/L); part Ⅱ: before different concentrations of midazolam was added, the endothelium intact rings were pretreated with methylene blue(10 -5 mol/L) and the endothelium denuded rings were pretreated with verapamil(5?10 -6 mol/L) or teraethylammonium(TEA,5?10 -3 mol/L).Results The four concentrations of midazolam examined produced relaxation in both endothelium intact and denuded rings Relaxation of endothelium denuded rings was less than that of endothelium intact rings (P0 05) When pretreated with TEA, midazolam produced greater relaxation in endothelium denuded rings(P

Objective To investigate the effects of propofol and inhalation anesthetics on the implicit memory under general anesthesia and determine the critical value of auditory evoked potential index (AEI) at which implicit memory no longer exists. Methods Sixty ASA I-II patients of both sexes scheduled for elective abdominal surgery or surgery on lower limb were enrolled in the study. They averaged (41.25?9.25) years and (63.8?9.57) kg. Patients with psychoneural or memory disorders were excluded. The patients were randomly divided into five groups of 12 patients in each group: isoflurane, sevoflurane, desflurane, propofol and control group. Each inhalation anesthetic group was further divided into two subgroups based on their end-tidal concentration: 0.8 or 1 .0 MAC. Propofol group was divided into two groups based on the infusion rate: 8 mg.kg. h-1 or 10mg.kg.h-1 . In control group operation was performed under epidural anesthesia. The patients were unpremedicated. Anesthesia was induced with propofot 1 .5-2.0 mg.kg and vecuronium 0. 　-0.2mg.kg-1, and maintained with inhalation anesthetic or propofol infusion supplemented with intermittent boluses of fentanyl and vecuronium. AEI was continuously monitored and recorded before anesthesia (T0), when the patient was sleepy (T1 ) and did not respond to verbal command (T2 ), after intubation (T3), after skin incision (T4), when peritoneum was being closed (or 30 min before the surgery) ( T5 ) and during emergence from anesthesia ( T6 ) . Eight hours after surgery muddy identified hearing rate was determined. Hemodynamic parameters were continuously monitored during operation. Results There was significant difference in AEI between the two subgroups before and after induction (P

0.05).Propofol produced greater relaxation in endothelium denuded rings pretreated with TEA( P 0.05).Propofol produced concentration dependent relaxation in rat aortic vascular smooth muscle. The effects may be due to the actions on voltage dependent calcium ion channels.