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

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

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

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

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 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

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.

ObjectiveTo find out the prevalence of brucellosis in Baotou,and to provide a scientific basis for integrated control of brucellosis.MethodIn 2010,high-risk people 7 to 70 years of age engaged in livestock farming,grazing,slaughtering,processing and selling were investigated in 9 districts (banners,counties)of Baotou city.In accordance with the principle of informed consent,blood samples were collected,serum titer was tested using the rose bengal agglutination test and tube agglutination test(SAT),and serum titer of 1:100(+ +) was considered as positive brucellosis,and results were evaluated based on brucellosis monitoring standards(GB 16885-1997).ResultsA total of 5832 copy blood samples were collected,and 250 cases were tested positive,the positive rate was 4.25％.The number of new cases was 164,accounting for 2.81％ (164/5832).Age was mainly concentrated in the 40 to 60 years,accounting for 66.0％(165/250).Brucellosis infection in the livestock industry accounted for 80.87％ (4757/5882).From the regional distribution,DAMAOQI had the most detected cases,and the detection rate was 12.10％ (73/603).ConclusionsContinue to increase the brucellosis prevention knowledge propaganda,carry out brucellosis surveillance of high-risk people,quarantine,and strengthen immunity is the only measure of effective control of brucellosis epidemic.

Objective To understand the arsenic level in drinking water and the current situation in prevention and control of endemic arsenic poisoning in Tuyouqi,Baotou of Inner Mongolia.Methods Through door-to-door survey,we selected patients with arsenic poisoning in order to monitor the arsenic poisoning condition of seven villages(Gangfangying,Laohuyao,Shilaozhang,Youfangying,Wanglaosi,Dajing and Xiaojing) in Tuyouqi,Baotou in 2010,and the disease was diagnosed based on Standard of Diagnosis for Endemic Arsenism(WS/T 211-2001).We also investigated the operation of Salaqi Water Company,Maodai Water Company and the Laohuyao water improvement project.We collected two samples per place in both low water period and high water period to measure water arsenic with silver diethyldithiocarbamate spectrophotometry(WS/T 28-1996).Results Three water improving projects were operating in normal conditions.Water arsenic in Salaqi Water Company and Maodai Water Company was level less than 0.01 mg/L,which met the National Safety Standards of drinking water with arsenic.Water arsenic in Laohuyao improvement project was 0.053 mg/L,which was higher than the drinking water safety standards.The seven villages in Tuyouqi had improved their water conditions.Among them,the arsenic level in Laohuyao was 0.052 mg/L,and the remaining six villages were ＜ 0.05 mg/L.There were 6 suspected cases,14 mild cases,4 moderate cases and 10 severe cases of the 2095 people monitored and no new cases found.The age of patients with arsenic poisoning was in the range of 40 to 70.Conclusions The monitoring results show that drinking water arsenic level in some villages in Tuyouqi is still excessive,but no new arsenic poisoning patients in arsenic poisoning areas are found.