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．

Objective To evaluate the effects of percutanenous intrapulmonary injecti0n 0f IL-2 plus radiotherapy for lung cancer. Methods Twenty-two patients with inoperable non small cell lung cancer received percutanenous intrapulmonary injection of 100U ? 6 in 6 weeks; and radiation dose was 60 Gy/6wks. Results The total effective response rate (CR+PR) was 95. 4 % with the complete response rate (CR) of 40. 9 %. Couclusion Percutanenous intrapulmomary injection of IL-2 plus radiotherapy could improve the control rate of the patients with lung cancer.

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

In order to explore the possibility of Xihuangwan (XHW)'s application in assistant therapy in patients with breast cancer, short- and long-term clinical efficacy were assessed in this study. Eighty and four patients with advanced breast cancer were selected in this study. They were divided into control group and treatment group randomly and evenly. All patients received surgical treatment followed by chemotherapy regimen composed of PTX + EPI + CTX (TEC regimen). Treatment group received additional assistant treatment of XHW. Short-term clinical efficacy was assessed by KPS, lesion stabilizing rate and side effects in 3-month follow-up study. Long-term clinical efficacy was assessed by overall survival (OS) and free-progression survival (FPS). KPS increased significantly after treatment in all patients (P < 0.05), more significantly in treatment group than in control group after treatment (P < 0.05); lesion stabilizing rate in treatment group increased significantly in treatment group than in control group (92.86% vs. 85.71%, P < 0.05); there was no significant difference between control group and treatment group in occurrence of side effects. Compared with control group, OS and FPS increased significantly in treatment group. Data in this study showed that XHW was suitable in treatment of advanced breast cancer due to its satisfactory short-term and long-term therapeutic effects.
Breast Neoplasms ; drug therapy ; pathology ; Disease-Free Survival ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Time Factors ; Treatment Outcome

Herpes Simplex ; immunology ; Humans ; Immune System Diseases ; etiology ; Immunosuppression ; Infant, Newborn ; Male

Objective To probe into nursing management methods of replantation of amputated finger patients accepting brachial plexus block analgesia and patient-controlled sedation (PCS) after operation.Methods 48 patients of replantation of amputated fingers accept continuous brachial plexus block analgesia and PCS after operation,Analgesia was 0.2% ropivaeaine,sedation was 0.05% midazolam or compositive liquid mixed 0.05% midazolam and 0.0005% fentanyl,the visual analogue scale (VAS),sedation scores and the changes of vital signs and side effocts after operation were recorded before the operation and at time intervals of 6,12,24,48,72 hours after the operation.Results The visual analogue scale(VAS)in the post-operation was obviously lower than the pre-operation,the Ramsay scores of PCS were higher than the pro-operation.There was no inadequate or excessive sedation.No influence was seen on respiration,circulation system and no other side effects happened.Conclusions Brachial plexus block analgesia and patient-controlled sedation (PCS) can offer a good Analgesia and sedation effect for patients of amputated fingers replantation,in period of analgesia and sedation,we should strengthen nursing and monitoring of vital signs to avoid accident.

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

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

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