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 study the change of the serum lipoprotein(a)〔Lp(a)〕 and other lipid levels in the childhood simple obesity.Methods　The levels of serum Lp(a),cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-ch),low density lipoprotein cholesterol(HDL-ch),apoA-I and apoB were investigated in 42 simple obesity children and 30 control subjects.Results　The levels of serum Lp(a),TC,TG,HDL-ch，LDL-ch of obesity children were markedly higher than those of normal.Conclusion　Simple obesity children are at increased risk of the development of cardiovascular disease.

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

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

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

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

BACKGROUND:Platelet-derived growth factor has the ability of wound repair, and relevant studies mainly focus on bone tissue repair. However, there are less studies about the effect of platelet-derived growth factors in skin wound healing. OBJECTIVE:To investigate the role of platelet-derived growth factor to promote wound healing by the regulation of bone marrow mesenchymal stem cels to the wound. METHODS:Bone marrow mesenchymal stem cels from rats were cultured. Immunofluorescence method was conducted to detect cel surface markers of CD34 and CD44 in bone marrow mesenchymal stem cels. Thirty healthy male SD rats were divided into five groups at random. Bone marrow mesenchymal stem cels labeled with PKH-26 were injected into the rat caudal vein in each group. The rats were anesthetized 1 week after injection. On the center of rat back, a 3-cm incision was made to establish a wound healing model. Different concentrations of platelet-derived growth factor were injectedvia multi-points on the skin wound after modeling, and the control group was treated with the same volume of normal saline. Skin wound tissues were taken for relevant parameter measurement at 14 days after injection. RESULTS AND CONCLUSION: Under the fluorescence microscope, platelet-derived growth factor could induce the migration and accumulation of bone marrow mesenchymal stem cels to the trauma in a dose-dependent manner and promote the wound healing. Masson staining showed that, with the concentration increase, platelet-derived growth factors could reduce inflammatory cel infiltration and increase the number of colagen fibers. Results from western blot assay showed that platelet-derived growth factor could inhibit the expression of matrix metaloproteinase-1, promote the expression of tissue inhibitor of matrix metaloproteinase 1 in the wound, and inhibit the colagen degradation, thereby promoting skin wound healing indirectly.

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 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