Aneurysm, Dissecting ; genetics ; Aortic Aneurysm ; genetics ; Diseases in Twins ; Humans ; Male ; Middle Aged

Preliminary research in our laboratory found that compound YZG-330 can reduce mouse body temperature, which could be blocked by adenosine A₁ receptor (A₁R) antagonist DPCPX. Based on the downstream signaling pathway of the A₁R, the mechanism by which YZG-330 lowers body temperature was further studied. The pharmacodynamics of YZG-330 was evaluated by measuring the rectal temperature; expression of the transient receptor potential (TRP) ion channel, the P38 protein and its phosphorylated form in mouse hypothalamic homogenate were detected by Western blotting. A Ca²⁺ fluorescent probe, Fluo-3AM, was added to cells to detect the effect of YZG-330 on the Ca²⁺ content of mouse hypothalamic cells. YZG-330 dose-dependently reduced the body temperature in mice, and the selective P38 inhibitor SB-203580 (20 mg·kg^-1, i.p.) significantly inhibited the hypothermic effect of YZG-330. A TRPM8 antagonist 2 (0.1 μg per mouse, i.c.v.) markedly attenuated the hypothermic effect of YZG-330 (0.25 or 1 mg·kg^-1, i.p.). YZG-330 (2 mg·kg^-1, i.p.) significantly increased the phosphorylation of P38, an effect that could be attenuated by the A₁R antagonist DPCPX (5 mg·kg^-1, i.g.) in mouse hypothalamus. In addition, YZG-330 also prominently enhanced the expression of TRPM8, which could be blocked by SB-203580; YZG-330 (0.1-10 μmol·L^-1) increased intracellular Ca²⁺ concetration in mouse hypothalamic cells in a dose-dependent manner, and was inhibited by the A₁R inhibitor DPCPX (0.5 and 1 μmol·L^-1) and TRPM8 antagonist 2 (1 μmol·L^-1). In conclusion, YZG-330 exerts its hypothermic effect by activating the A₁R to promote the phosphorylation of P38 protein and thereby up-regulating the expression and activity of the TRPM8 ion channel, resulting in increased intracellular Ca²⁺ concentration to stimulate mouse hypothalamus cells to down-regulate body temperature. All animal experiments were approved by the Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences.

OBJECTIVETo compare components in volatile oils of nutmeg and prepared nutmeg.

METHODVolatile oil from nutmeg and prepared nutmeg were extracted by vapor distillation. The chemical components in two kinds of volatile oils were determined and indentified by GC-MS.

RESULTThe change in quantity and quality of components in volatile oils were observed after processing. 13 new components occurred and 4 components disappeared in volatile oils after processing. The contents of methyleugenol and methylisoeugenol that are active ingredients were increased. The contents of myristicin and safrol that are toxic ingredients in volatile oils were decreased.

CONCLUSIONThe processing method of nutmeg by soaking with water and roasting with bran is scientific.

Anisoles ; analysis ; Benzyl Compounds ; analysis ; Dioxolanes ; analysis ; Eugenol ; analogs & derivatives ; analysis ; Gas Chromatography-Mass Spectrometry ; Hot Temperature ; Myristica fragrans ; chemistry ; Oils, Volatile ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Pyrogallol ; analogs & derivatives ; analysis ; Safrole ; analysis ; Technology, Pharmaceutical ; methods

ObjectiveTo analyze the prevalence and epidemic trend of human brucellosis between 2007 -2010 in Qian'an county,and to provide a basis for future prevention and control measures. Methods Epidemiological data of brucellosis between 2007 - 2010 were obtained from the national disease surveillance report on management information system, population data were from the national disease surveillance information management system for basic information reporting system, and descriptive epidemiological methods was used for statistical analysis. Results A total of 86 cases were infected with brucellosis in Qian'an county from 2007 to 2010, with 68 cases of male and 18 cases of female, and male to female ratio was 3.78 : 1. Patients were mainly in the age of 20 - 55, with 40 - ＜ 45 year-old group the highest. All patients were local residents. Most professional were livestock acquisition, processing and aquaculture personnel. The majority of patients lived in Jianchang town,with 51 cases, accounting for 59.30％. Thirteen patients were reported in 2007, incidence was 0.0201‰(13/ 647 983). Thirty-nine patients were reported in 2010, and incidence was 0.0563‰(39/657 380). There was a fluctuations increase from 2007 to 2010. In 2007 brucellosis occurred in only two townships(towns), which spread to eight townships (towns) and urban areas in 2010. ConclusionsThe epidemic of human brucellosis in Qian'an is in a spreading trend. We recommend the government to strengthen the quarantine of livestock, and the infected livestock should be timely treated. Strengthen the prevention and control in Jianchangying. At the same time increase the brucellosis propaganda, and enhance self-protection awareness of the occupational groups.

Aim To observe the effect of hemodialysis on pharmacokinetics of sparfloxacin in thepatients contracting chronic renal failure. Methods Sparfloxacin concentrations inserum and urine of hemodialysis and non-dialysis patients were measured with a highperformance liquid chromatography method after administration a single oral dose of 200mg sparfloxacin. The pharmacokinetic parameters were computed with the programPKBP-N1.Results The main pharmacokinetic parameters in hemodialysis group wereT1/2(ka) - (1. 25 ?0. 57) h, T1/2(?) = (11. 88?4. 13) h, Tpeak = (4. 18 ? 0. 78) h,Cmax = (0.80 ? 0. 17) mg? L-1 and AUC0-= (6. 90 ? 3. 25) mg?h?L-1, while innon-dialysis group were T1/ 2(ka) = (1. 12 ? 0. 42) h, T1/ 2(?) = (15. 93 ? 5. 20) h, Tpeak =(3. 88 ? 0. 75) h, Cmax = (0. 69 ? 0. 37) mg?L -1, AUC0-= (10.05 ? 4. 13) mg?h?L-l. The original sparfloxacin discharge rats in urine within 24 h were (8. 98 ? 3. 92) % and(10. 58 ? 5. 64) % separately. T1/2(?) and AUC in hemodialysis group were markedly lowerthan in non-dialysis group (P

OBJECTIVETo explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms.

METHODSWe measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot.

RESULTSThe viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway.

CONCLUSIONIndirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Coloring Agents ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Genes, myc ; Humans ; Indoles ; administration & dosage ; pharmacology ; Male ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; Tetrazolium Salts ; Thiazoles

OBJECTIVETo investigate the mechanism of arsenic trioxide (As(2)O(3)) induced apoptosis in hepatic blastoma cells HepG2 and its effects on cell nuclear matrix related protein promyelocytic leukaemia (PML).

METHODSHepG2 cells were cultured in MEM medium and treated with different concentrations of As(2)O(3) for either 24 h or 96 h. In situ terminal deoxynucleotidyl transferase (TdT) labeling (TUNEL) and DNA ladder were applied to detect apoptosis. Confocal microscopy and western blot were performed to observe the expression of PML.

RESULTSTUNEL positive apoptotic cells and DNA ladder could be detected in As(2)O(3) treated groups. The expression of PML decreased in HepG2 cells with 2 micro mol/L As(2)O(3), and micropunctates characteristic of PML protein in HepG2 cell nuclei almost disappeared after the treatment of 5 micro mol/L As(2)O(3).

CONCLUSIONAs(2)O(3) induces HepG2 tumor cell apoptosis in a time- and concentration-dependent manner. As(2)O(3) may degradate the PML protein in HepG2 cell nuclei. The decreased expression of PML is closely correlated with apoptosis. Nuclear matrix associated protein PML could be the target of As(2)O(3) therapy.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Hep G2 Cells ; Hepatoblastoma ; chemistry ; drug therapy ; pathology ; Humans ; Liver Neoplasms ; chemistry ; drug therapy ; pathology ; Nuclear Proteins ; analysis ; Oxides ; pharmacology ; Promyelocytic Leukemia Protein ; Transcription Factors ; analysis ; Tumor Suppressor Proteins ; analysis

Base Sequence ; Conjugation, Genetic ; Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Escherichia coli ; drug effects ; enzymology ; Humans ; Klebsiella pneumoniae ; drug effects ; enzymology ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Polymerase Chain Reaction ; Transformation, Bacterial ; beta-Lactamases ; genetics

Objective To analyze the epidemiologic characteristics of epidemic hemorrhagic fever syndrome (EHF) from 2004 to 2010 and provide scientific basis for formulating control measures.Methods Epidemiological data of EHF between 2004 to 2010 were obtained from the“National Disease Surveillance Report on Management Information System”,and the population data were from the“National Disease Surveillance Information Management System for Basic Information Report System”.Descriptive epidemiological methods was used for statistical analysis.ResultsA total of 173 cases were reported in Qian'an from 2004 to 2010.From 2004 to 2010,the cases were 86,67,12,1,0,1,and 7 cases,respectively,and the rate were 13.12/10 million ( 86/640 249 ),10.42/10 million (67/642 688 ),1.86/10 million ( 12/645 124),0.15/10 million (1/647 983 ),0(0/650 720),0.15/10 million( 1/653 839),and 0.11/10 million(7/657 380),respectively.The overall rate was 3.86/10 million(25/648 283) of population.From 2004 to 2008 the incidence reported declined rapidly,then increased slowly after 2009.The cases were found intensively in winter(November - next January) and spring season (february - may).The incidence in the age group of 10 - 45 was higher than that of other age groups,and the total number of cases was 82.08％(142/173).The incidence in males( 114 cases) was higher than that of females(59 cases).Occupational distribution mainly to peasants and students,which accounted for 87.86％ (152/173).Conclusions Epidemic in the city declines rapidly follows by a slow recovery,suggesting that in the future surveillance,mice-killing and protection of vulnerable population should be strengthened.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.