High performance liquid chromatography-time-off-flight mass spectrometer (HPLC-TOFMS) technology coupled with partial least squares discriminant analysis (PLS-DA) processed by SIMCA-P software was applied to investigate serum endogenous metabolites alternations of valsartan in spontaneous hypertension rats (SHR). And MetPA platform was used to connect identified potential biomarkers in corresponding metabolic pathways to find possible therapeutic mechanism of valsartan. Valsartan significantly declined the blood pressure of SHRs (P < 0.05) at fourth week. The metabolic profiling significantly changed and four metabolites involved in G protein-coupled pathway were identified. Metabolomics is able to detect holistic and microcosmic alternations in organism, so as to elucidate therapeutic mechanism of drugs.
Animals ; Biomarkers ; blood ; Blood Pressure ; Chromatography, High Pressure Liquid ; Discriminant Analysis ; Least-Squares Analysis ; Mass Spectrometry ; Metabolome ; Metabolomics ; Rats ; Rats, Inbred SHR ; Valsartan ; pharmacology

Config and modify open source software such as Nagios、 MRTG and Awstats, make it more suitable and stable for our network environment. Construct server monitor、 service monitor、 network monitor and website statistics system by using open source software. Besides, we construct network resource management system via ASP and database technology.Finish the network and service monitoring and management system based on B/S architecture. This system can keep close watch on the status of servers and services running on servers, and ensure all of the servers and services normal running, and provide the basic information service for policy-making body and other research institute.

Objective To investigate the protective effect of endotoxin pretreatment on hippocampal neurons in rat forebrain following ischemia reperfusion and its possible mechanism. Methods Rat forebrain ischemia reperfusion model was used. The effects of endotoxin pretreatment on the changes of superoxide dismutase (SOD), glutathione peroxidase (GSH PX) and malondialdehyde (MDA) activities and the neuron count in CA1 region were observed. Results Pretreament with endotoxin before cerebral ischemia enhanced the activities of SOD and GSH PX but decreased MDA level and the number of ischemic neurons in CA1 region. Conclusion Endotoxin pretreatment can protect the neurons in rat forebrain against ischemia reperfusion injury. The mechanism may be associated with the enhancement of endogenous antioxidant activity in central nervous system.

Puromycin-sensitive aminopeptidase (PSAP) belongs to the M1 family of aminopeptidases, characterized by the N-terminal substrate binding sequence GAMEN, the enzyme activity center HEXXH(X)₁₈E motif, and the C-terminal ERAP-1-like superfamily structural domain. Encoded by the gene NPEPPS located at 17q21.32, PSAP consists of 919 amino acids and is widely distributed throughout the human body, with the highest expression in the brain, followed by the heart and skeletal muscle. It is also found in the liver, renal tubular epithelium, small intestine, large intestine epithelium, and gastric epithelial cells. PSAP primarily relies on its aminopeptidase hydrolytic activity to remove toxic protein aggregates such as Tau, poly Q, and Cu, Zn-superoxide dismutase 1, making it an important factor in the development of diseases such as Alzheimer's disease, Huntington's chorea, and tumors. Existing PSAP inhibitors include bestatin, amastatin, leuhistin, actinonin, and purinomycin, some of which are already available or in clinical trials. This review provides an overview of the structural and biological functions of M1 family aminopeptidases, with a focus on PSAP, to facilitate further research and targeted drug development.

To develop a new small molecular probe for discovering an antitumor lead compound from the replacement of carboxylic group of two molecular antibacterial fluoroquinolones with a heterocyclic ring, a series of the C3/C3 bis-fluoroquinolones tethered with an 1, 3, 4-oxadiazole ring were synthesized as their respective HCl salts, and their structures were characterized by elemental analysis and spectral data. The in vitro antitumor activity against L1210, CHO and HL60 cell lines was also evaluated via the respective IC50 values by methylthiazole trazolium (MTT) assay.
Animals ; Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; CHO Cells ; drug effects ; Cell Line, Tumor ; Cricetinae ; Cricetulus ; Drug Design ; Fluoroquinolones ; chemical synthesis ; chemistry ; pharmacology ; HL-60 Cells ; drug effects ; Humans ; Inhibitory Concentration 50 ; Leukemia L1210 ; pathology ; Molecular Structure ; Oxadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To evaluate the prognosis in patients with hepatocarcinoma by examining the expression of α-fetoprotein (AFP) and des γ prothrombin (DCP).Methods Retrospectively analyzed the expression of AFP and DCP in 105 patients received curative hepatectomy.Divided the patients into three groups as follow:the tumor markers were both negative pre-and post-operation (Group N) ; the tumor markers decreased to normal after operation (Group D) ; the tumor markers kept positive or decreased but still higher positive after operation (Group P).Then combined the two markers and divided the patients into 4 groups:two markers both negative(AFP + DCP +)(Group A) ; AFP + DCP-(Group B) ; AFP-DCP + (Group C) ; AFP-DCP-(Group D).Results High AFP and DCP levels were significantly associated with poor tumor-free and overall survival.The presence of large size and advanced stage were significantly associated with Group P.Overall survival in the AFP-N group was significantly better than that of other groups and overall survival in DCP-N group were significantly better than that of the P group.After the combination,Group A had the best overall and tumor free survival rate while the D group had the worst.The differences between B and C group were not significant.Conclusions AFP and DCP can be both used solely as tumor markers and the expressions of them are associated with the prognosis.The combination of two markers can be used for better prediction of hepatocarcinoma.

A systematic summary of the concept and operational mechanism of the intensive disciplines management in a hospitals group,and that of the intensive disciplines management for hospitals groups,as well as a comparison of the differences found in department service capacity,service quality,discipline development and patient satisfaction before and after the intensive discipline management is in place.The practice proved that the departments practicing intensive management have witnessed significant rise in outpatient headcount,hospitalization headcount and surgical operation headcount.Their weight in the group is also higher.For example,their curative rate and rescue success rate of dubious and acute diseases higher than before (P＜ 0.05).The Group has 8 provincial key medicine-specialties,including 5 intensive management departments.It has 8 provincial key clinicaldisciplines,including 2 intensive management departments.The overall patient satisfaction for service of such departments is 92.1％,the satisfaction for convenience is 84.4％,that for service quality 90.0％,that for service attitude 92.5％,and that for medical service experience is 89.5％.All of which are significantly higher than that those on their admission to the hospital.The intensive management has enabled unified management of internal medicine and surgery of the same profession in the campus,integrated workforces of both internal medicine and surgery department along with those of medical technicians.In addition,it has enhanced departmental service capacity and quality,discipline competence,as well as outpatients' convenience,patients' satisfaction and medical experience.

Objective To investigate the effects of large dose of atorvastatin on the expression of Sprouty-1 in CD4 + T lymphocytes from unstable angina patients during perioperative period of PCI.Methods A total of 52 unstable angina patients enrolled were divided randomly (random number) into large-dose atorvastatin (80 mg/d,n =26) pretreated group and moderate-dose atorvastatin (20 mg/d,n =26) pretreated group.Circulating CD4 + T cells were obtained by magnetic cell sorting system (MACS) before PCI and 18-24h after PCI.For detecting the gene expression,the reverse transcription fluorescent quantitative polymerase chain reaction (RT-PCR) was used to measure the expression of Sprouty-1 mRNA in CD4 + T lymphocyte.The level of Sprouty-1 protein was detected with Western blot analysis and IL-2 was quantified by enzyme-linked immunosorbent assay (ELISA).Results ①Compared with large-dose group before PCI,the expression of Sprouty-1 mRNA and Sprouty-1 protein levels were dramatically increased in large-dose group after PCI (P ＜ 0.05).②Compared with moderate-dose group before PCI,the expression of Sprouty-1 mRNA and protein levels were slightly increased in moderate-dose group after PCI,but there was no statistical significance (P ＞ 0.05).③Compared with large-dose group before PCI,the serum level of IL-2 was decreased in large-dose group after PCI (P ＜ 0.05).Whereas the serum level of IL-2 was slightly increased in moderate-dose group after PCI compared to moderate-dose group before PCI,there was still no statistical significance (P ＞ 0.05).Conclusions Large-dose atorvastatin pretreatment reduced post-PCI myocardial inflammation through up-regulating the expression of Sprouty-1 mRNA and level of Sprouty-1 protein in CD4 + T lymphocytes.

Objective To investigate the effect of ropiyacaine combined with intra-spinal epidural anesthesia by using the same volume but different injection speed on anaesthetic level.Methods 80 cases of patients of ASA～Ⅱdegree suitable to use intra-spinal epidural combined anesthesia for gynecologic operation were selected and ran- domly divided into three groups,0.75 % ropivacaine 2mg(15mg)administered,group A the speed of injection was 10 seconds,group B injection speed was 20 seconds,group C injection speed was 30 seconds,the anaesthetic level reached T_(10).The time of highest level in spinal anesthesia,30 minutes after spinal anesthesia MAP,and number of cases need to add epidural drug were all recorded.Results The best effect of anesthesia was found in group B,the block level of anesthesia was satisfactory,blood dynamic was stable,and there was no need to add epidural drug.Conclusion The speed of 0.75 % ropivacaine 2ml spinal epidural combined with anesthesia was suitable at the speed of 20 seconds.

Objective To explore therapeutic effects and mechanisms of radical scavenger edaravone on experimental cerebral hemorrhage.Methods Two hundred-forty male SD rats were divided randomly into four groups:control group,cerebral hemorrhage group,edaravone treatment group before operation (A) and edaravone treatment group after operation (B).Experimental cerebral hemorrhage model was made according to the method reported by Rosenberg.Water quantity contained in brain and nervous missing sign were observed,meanwhile the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in brain tissue were measured.Results Compared with cerebral hemorrhage group,nervous missing sign and water quantity contained in brain obviously changed in edaravone treatment group (P