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

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

Objective To investigate the emergency treatment and correlation factors of aqueous misdirection during glaucoma and cataract surgery in glaucoma patients.Design Retrospective case series.Participants 126 cases(132 eyes)of angle-closure glaucoma patients with aqueous misdirection during surgery,100 cases(100 eyes)of angle-closure glaucoma patients without aqueous misdirection during surgery and 100 cases(100 eyes)of senile cataract patients.Methods We performed pars plana vitreous water-bag aspiration or anterior vitrectomy on glaucoma patients with aqueous misdirection during surgery.All the factors in observation group and control groups were compared and analyzed by logistic regression.Main Outcome Measures Preoperative highest intraocular pressure(HIOP),intraocular pressure after maximum dose(IOP),anterior chamber depth(ACD),lens thickness(LENS),axial length (AXL),mean keratometry(K),intraocular lens diopter within-0.5D corrected by SRK-T formula(IOLD).Results Among all the 132 angle-closure glaucoma eyes whose posterior chamber pressures were increased during surgery,we performed pars plana vitreous water-bag aspiration in 123 eyes(93.18%),and anterior vitrectomy in 9 eyes(6.8%).Postoperative complications included shallow anterior chamber in 20 eyes(7 eyes with malignant glaucoma,9 eyes with choroidal detachment,4 eyes with delayed local suprachorodal hemorrhage),and vitreous local hemorrhage in 1 eye.Means of all the observation indexes on three groups showed significant difference(all P

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

Objective To explore the relationship between the carotid artery atherosclerotic(CAA) plaque and its risk factors and cerebral infarction(CI).Methods 196 patients with CI(CI group) and 104 patients without CI(non-CI group) were examined by color Doppler ultrasonography on their carotid artery.The relationships were analysed between the CAA plaque with age,sex,accompany disease,smoking and alcohol drinking of all the pataints.Also,the distribution of different grade plaque was observed in each group.Results The incidences of CAA plaque were higher in patients with aged,accompainied hypertension,diabetes,abnormal blood-lipids and smoking(P