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．

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

OBJECTIVETo explore the possible mechanism of curcumin in inducing the apoptosis of breast cancer cell MDA-MB-231.

METHODCurcumin of different concentrations at 0, 10 25, 50, 100, 150, 200 micromol x L(-1) were used to intervene breast cancer cells MDA-MB-231 for 24 hours. MTT was used to observe its effect on the proliferation of breast cancer cells. The flow cytometry was used to detect its effect on the cell apoptosis. The real-time quantitative PCR and Western blot was used to assess the expression levels of GRP78 and CHOP in breast cancer cells.

RESULTCurcumin could inhibit the proliferative ability of breast cancer cells by inducing them in a concentration-dependent manner. Curcumin could significantly increase the expression levels of GRP78 and CHOP in breast cancer cells.

CONCLUSIONCurcumin could induce the apoptosis of breast cancer cells MDA-MB-231 by activating endoplasmic reticulum stress.

Apoptosis ; drug effects ; Breast Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Curcumin ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Endoplasmic Reticulum Stress ; drug effects ; Female ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Transcription Factor CHOP ; genetics ; metabolism

In order to quickly and accurately identify the onset and offset of the QRS complex in electrocardiogram (ECG) signal with different forms, a triple local transform method was employed in the present study to detect the suspected onset and offset points of QRS. The accurate onset and offset points of QRS complexes were selected according to the rules drawn by the trial process based on the characteristics of angle and amplitude constituted within these suspected points. The method makes full advantage of the angle and amplitude characteristics of the QRS complex, by which the results can be acquired with some simple arithmetic quickly, accurately and adaptively. The method was investigated with data from the MIT-BIH arrhythmia database and satisfactory results were obtained.
Algorithms ; Arrhythmias, Cardiac ; diagnosis ; Databases, Factual ; Electrocardiography ; Humans ; Signal Processing, Computer-Assisted

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

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

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.

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

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.