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．

ObjectiveTo compare the effects of streamlined liner pharynx airway(SLIPA) and endotracheal intubation in the radical mastectomy under general anesthesia,and to evaluate the efficacy and safety.MethodsSixty patients scheduled for radical mastectomy were randomly divided into 2 groups.SLIPA group( S,n =30 ) and endotracheal intubation group(T,n =30).The data were kept regarding the insertion time and successful rate,MAP,HR,BIS were recorded at 6 time points:before induction ( T0 ),during SLIPA incursion or trachel intubation ( T1 ),3min after intubation( T2 ),before extubation( T3 ),after extubation ( T4 ),3 min after extubation ( Ts ).Ppeak,PetCO2 and SpO2 were measured after successful airway placement at 10min,30min,60min and to observe intraoperative and postoperative throat complications.ResultsThe time of endotracheal intubation group is significantly longer than SLIPA group (P ＜0.05).In group T,MAP and HR at T1,T2,T4,T5 were higer than at T0 and the same time points in group S(all P ＜ 0.05 ).No regurgitation and aspiration was found in two groups ( all P ＞ 0.05 ).The incidence of complicaton in group T is significantly higher than that in group S ( all P ＜ 0.05 ).ConclusionSLIPA is easier placement,safety and efficacy when it is used for the radical mastectomy under general anesthesia without significant influences on hemodynamics and fewer complications of throat after operation.

OBJECTIVETo detect the expression level of interleukin 17 (IL-17) in the plasma and colonic mucosa of patients with ulcerative colitis (UC), and to explore the synergistic mechanism of qingchang huashi recipe (QHR) combined with Mesalazine.

METHODSRecruited were 24 mild or moderate UC patients of damp-heat inner accumulation syndrome (DHIAS). Their samples of intestinal tissues were histologically graded. They were assigned to the combination group and the Western medicine (WM) group, 12 in each group. Besides, another 12 healthy volunteers were recruited as the healthy control group. QHR combined Mesalazine were given to patients in the combination group, while those in the WM group took Mesalazine. The therapeutic course for all was 3 months. By the end of treatment the expression level of IL-17 in the plasma and colonic mucosa was detected using ELISA. The infiltration of IL-17 in the intestinal mucosal tissue was detected by immunohistochemical SP method.

RESULTSThe expression level of IL-17 in the plasma and colonic mucosa was significantly higher in UC patients than in healthy controls (P <0. 05). The higher the histological grading the higher the expression level. The expression level of IL-17 in plasma and colonic tissues decreased after treatment in the two treatment groups (P < 0.05). Besides, the expression level of IL-17 was lower in the combination group than in the WM group (P <0.05).

CONCLUSIONQHR combined Mesalazine could synergically enhance the effect and effectively inhibit intestinal inflammation through down-regulating the expression of IL-17.

Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Colitis, Ulcerative ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Immunologic Factors ; metabolism ; Inflammation ; metabolism ; Interleukin-17 ; metabolism ; Intestinal Mucosa ; drug effects ; Intestines ; metabolism ; Mesalamine ; therapeutic use

Objective:To retrospectively analyze the clinical data of 73 children with non-Hodgkin′s lymphoma to determine its clinical features, pathological types and relationship with efficacy.Methods:In Shanghai Children′s Hospital from October 2014 to October 2018, 73 children with newly diagnosed non-Hodgkin′s lymphoma were enrolled for a retrospective study, with 52 males and 21 females, aged between 2 and 13 years old, so as to comprehensively assess cumulative organs, pathological diagnosis, stage of disease, surgery and efficacy.Results:Among the 73 children with non-Hodgkin′s lymphoma, 66 cases had a clear pathological diagnosis, including 38 cases of surgical pathology and 20 cases of biopsy pathology.All of them were confirmed by immunohistochemisty, and 8 cases were determined by flow cytometry.Meanwhile, 6 cases of the rest 7 cases obtained approximate pathological classification.Only 1 case was unknown.Among the 66 cases, Burkitt lymphoma was the most common in 31 cases, followed by 14 cases of T-lymphocyte type, 7 cases of enlarged lymphoma, 6 cases of B-lymphocyte type, 5 cases of diffuse large B lymphoma, 1 case of extranodal natural killer/T cell lymphoma-nasal type, 1 case of blastic plasmacytoid dendritic cell neoplasm, and 1 case of panniculitis-like T lymphoma.The initial site or cumulative organ involved multiple organs, with most common in neck(20 cases), abdominal cavity(15 cases), and mediastinum(6 cases). In view of outcomes and efficacy, the complete remission rates of stage Ⅱ, Ⅲ, and Ⅳ in clinical were 100.0%, 85.1%, and 72.2%, respectively.The event-free survival rates in stage Ⅲ and Ⅳ were lower than those in stage Ⅱ(80.9% vs. 66.7% vs. 100.0%). From the perspective of the main pathological types grouping, the results revealed that lymphoblastic lymphoma had a lower event-free survival rate than Burkitt′s lymphoma (73.7% vs.90.3%), while there was no statistical significance(all P>0.05). Conclusions:Non-Hodgkin′s lymphoma in children is more common in men, and less common in infants and young children.Pathological type is simpler than adults, Burkitt lymphoma is the most common type, and clinical stage and pathological type may be related to prognosis.

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

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.

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.

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

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