Rofecoxib, a COX-2 specific inhibitor, is approved for treatment of osteoarthritis, acute pain and primary dysmenorrhea. On September 30, 2004, Merck announced the voluntary worldwide withdrawal of rofecoxib (Vioxx). This paper reviewed the pharmacological actions of the COX-2 specific inhibitors and the characterization, premarket study, clinical application and side-effects of rofecoxib and analyzed the withdrawal of rofecoxib.

Objective To investigate the changes of Claudin-3 and Claudin-11,two key components of blood-testis barrier (BTB) on male infertility induced by γ-ray irradiation.Methods Fortytwo KunMing male mice (20-25 g) were divided into one control group,three γ-ray irradiation groups and three estrodiol (E2) intervention groups randomly:Group A,sham controlled; the lower abnominal and scrotal area of the mice in Group B,C,D were irradiated with single dose of 2,6 or 10 Gy 60Co γ-ray after anaesthetizd; 17β-estradiol intervention were initiated in Group E,F,G after 6 Gy γ-ray irradiation via hypodermic injection for 4w at the dose of 1,2,4 μg/d,respectively.Mice were sacrificed 2 w after the last E2 administration.The tubule differentiation index (TDI) was counted in testis sections.InhibinβB,Claudin-3 and Claudin-11 transcription levels were assayed with semiquantitative real time PCR.Claudin-11 protein levels in testis were generated by western blot.Results Compared with sham control group,TDI in three γ-ray irradiation groups were markedly reduced (68.5 ± 6.4,35.0± 6.1,16.3 ± 5.7 vs 100.0,all P＜0.05).InhibinββB mRNA expression level in testis of gourp D was markedly decreased (0.5±0.2 vs 1.0±0.1,P＜0.05).Claudin-3 mRNA levels of group C and D were up-regulated to 2.17 and 3.49 times,respectively.Claudin-11 protein levels were significantly increased to 2.18 and 2.23 times.Compared with group C,TDI in three E2 intervention groups were improved,which were obvious in group F and G (61.7±7.2,55.8±11.9 vs 35.0±6.1,P＜0.05).The InhibinβB mRNA levels were increased,though there were no significant differences (all P ＞0.05).Claudin-3 mRNA levels in group F and G were down-regulated (1.3± 0.2,1.6±0.3 vs.2.2 ± 0.2,all P＜0.05).In group F significantly reduced mRNA level and protein level of Claudin-11 were observed (mRNA:1.2±0.2 vs.1.8±0.2,P＜0.05; Protein:1.5±0.5 vs.2.2±0.3,P＜0.05).It was negatively correlated TDI with mRNA expression levels of Claudin-3 and Claudin-11 in the irradiated testis (rs =-0.884,P＜0.05; rs=-0.758,P ＜0.05,respectively).Conelusions Irradiation could elevated the expression of claudin-3 and claudin-11.

Arrhythmogenic Right Ventricular Dysplasia ; diagnosis ; Electrocardiography ; Humans ; Male ; Middle Aged

Objective To investigate the protective effect of autophagy inducer rapamycin on acute kidney injury (AKI) induced by sepsis. Methods Twenty-four Sprague-Dawley (SD) male rats were randomly divided into sham group, caecal ligation and puncture (CLP) model group, and rapamycin treatment group (Rap treatment group), with 8 rats in each group. The septic AKI model was reproduced by CLP in rats, and rats in sham group were given appendix isolation without ligation and puncture. The rats in Rap treatment group were given 1.6 mg rapamycin by intraperitoneal injection immediately after model reproduction, and the rats in CLP model group were injected with an equal amount of normal saline. The rats in all groups were sacrificed after collecting peripheral blood specimen at 24 hours after model reproduction, and the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were determined. The pathomorphology change in renal tissue was observed under light microscope after periodic acid Schiff (PAS) staining. Real-time polymerase chain reaction (real-time PCR, RT-PCR) was used to determine the mRNA expressions of renal tubular autophagy related molecules Atg-5 and Beclin-1. Western Blot was used to detect the expressions of renal tubular autophagy associated protein microtubule labeled protein 1 light chain 3-Ⅱ (LC3-Ⅱ) and Beclin-1 as well as apoptosis protein cytochrome C (Cyt C), Bax and Bcl-2. TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to determine the renal tubular epithelial cell apoptosis. Results Rapamycin could alleviate pathomorphology changes in rats with septic AKI, and decrease the levels of BUN and SCr. Compared with sham group, the expressions of Atg-5, Beclin-1 and LC3-Ⅱ in CLP model group were significantly increased [Atg-5 mRNA (2-ΔΔCt): 2.34±0.04 vs. 1.00±0.03, Beclin-1 mRNA (2-ΔΔCt): 1.40±0.02 vs. 1.00±0.03, LC3-Ⅱ protein (gray value): 0.82±0.03 vs. 0.45±0.04, Beclin-1 protein (gray value): 0.59±0.06 vs. 0.29±0.03, all P < 0.01]. Rapamycin could further up-regulate the expressions of Atg-5, Beclin-1, and LC3 Ⅱ [Atg-5 mRNA (2-ΔΔCt): 3.28±0.19 vs. 2.34±0.04, Beclin-1 mRNA (2-ΔΔCt): 2.38±0.08 vs. 1.40±0.02, LC3-Ⅱ protein (gray value): 1.11±0.07 vs. 0.82±0.03, Beclin-1 protein (gray value): 0.85±0.05 vs. 0.59±0.06, all P < 0.01]. Compared with sham group, the apoptotic cells in CLP model group were increased significantly [(34.49±10.45)% vs. (2.78±1.40)%, P < 0.01], Cyt C and Bax protein expressions were significantly up-regulated (gray value: 0.87±0.02 vs. 0.46±0.03, 1.20±0.06 vs. 0.46±0.01, both P < 0.01), and Bcl-2 expression was significantly down-regulated (gray value: 0.64±0.02 vs. 1.33±0.09, P < 0.01). Rapamycin could effectively inhibit cell apoptosis [(15.44±5.50)% vs. (34.49±10.45)%, P < 0.01] and the protein expressions of Cyt C and Bax (gray value: 0.72±0.03 vs. 0.87±0.02, 0.84±0.03 vs. 1.20±0.06, both P < 0.01), and up-regulate the protein expression of Bcl-2 (gray value: 0.77±0.04 vs. 0.64±0.02, P < 0.01). Conclusion The protective effect of rapamycin on renal tissue of rat with AKI induced by sepsis was depended on cell apoptosis inhibition through inducing and promoting cell autophagy.

Objective To study the effects of hSSTR2 gene in vitro transfection on differential proteins expression in pancreatic cancer cell line Panc-1 and search new sensitive therapeutic targets of pancreatic cancer. Methods The full length hSSTR2 cDNA was introduced into pancreatic cancer cell line Panc-1 by adenovirus vector ( Ad. CMV. hSSTR2. GFP) mediated transfection. The differential expressed proteins between the hSSTR2 transfection group, vector control and mock control were isolated and screened by 2D-DIGE analysis. Protein identification was performed by peptide mass finger printing with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF). Results The hSSTR2 gene was transfected into Panc-1 pancreatic cancer cells in vitro successfully, and fluorescence difference protein expression patterns were established between hSSTR2 negative and positive expression of Panc-1 cell. Analysis by DeCyder v6.5 software showed a total of 18 protein spots ( > 1.3-fold) and these protein spots were identified by mass spectrometry as 13 proteins. Proteins with lower abundance levels included GMP synthase, stress induced phosphoprotein 1, glutamate dehydrogenase 1, Septin-11, vimentin, Isocitrate dehydrogenase [NAD] subunit alpha, Import inner membrane translocase subunit TIM50. Proteins with high abundance levels included Elongation factor 1-alpha-1, Isoform M2 of Pyruvate kinase isozymes M1/M2, Enoyl-CoA hydratase,tripartite motif-containing 28 protein, Mitofilin, HSP105. Conclusions The proteins expression changed after hSSTR2 gene in vitro transfection in Panc-1 cells, and the function of difference proteins involved the process of metabolism of sugar, fat and nucleic acid, and the regulation of cell growth. The present study paved the way for searching new sensitive therapeutic targets of pancreatic cancer.

Objective To study the effect of hypothermia on cerebral mitochondrial respiratory function and ultrastructure after traumatic brain injury(TBI). Methods Sprague-Dawley rats were subjected to moderate brain injury by using lateral fluid-percussion(LFP)and randomly divided into sham operation group,normothermic TBI group(rectal temperature for 36-37℃)and hypothermic TBI group(rectal temperature for 31-32℃ lasting for two hours).The ipsilateral brains were dissected and homogenized brain tissues were extracted to obtain mitochondfia by density-centrifugation and speed-centrifugation at 2,24 hours and at days 3 and 7 after TBI.The mitochondrial uhrastructure was studied by electron microscope.The indices of respiratory control rate(RCR)and P/O ratio of mitochondrial respiratory function were measured after oxygen consumption was determined with a Clark-type electrode.Results The mitochondrial uhrastructure of normothermic TBI group was damaged severely while that of hypothermic TBI group kept relatively integrated.The RCR and P/O ratio were markedly decreased two hours after TBI and reached the lowest level at the 24th hour(P＜0.01).At day 7,RCR kept at a lower level compared with sham operation group but P/O ratio recovered to normal.Change of RCR was similar in hypothermie TBI group and normothermic TBI group.However,RCR of the hypothermic TBI group was significantly higher than that of the normothermic TBI group within three days after TBI.In the meantime,P/O ratio recovered to normal three days after TBI. Conclusion Hypothermia can improve cerebral mitochondrial respiratory function and protect the mitochondrial structure after TBI.

Objective To investigate whether the malignant transformation of macrophages ( Mφ) in glioma mesenchyme was induced by the fusion of glioma cells ( SU3 ) and Mφ.Methods SU3 cells transfected with red fluorescent protein genes were co-cultured in vitro with Mφexpressing enhanced green fluorescent protein.The cell lineages with RFP+/GFP+dual-color fluorescence were established by using monoclonal selection method.A series of tests for analyzing cancer-related phenotypes, tumorigenicity and specific markers for murine macrophage were performed.Results (1) A few of dual-color fluorescent cells were observed in the co-culture.Three monoclonal cell lineages (C3, C4 and C12) were obtained success-fully.(2) Three types of cells including RFP+, EGFP+and RFP+/EGFP+cells were formed during the cul-ture of monoclonal C12 cell lineage.The percentage of EGFP+cells was increased along the extended culture time and increased passages.Then, EGFP+cells gradually became the predominant cell population.Nota-bly, the percentage of RFP+/EGFP+cells were decreased and maintained at a low level, but the RFP+cells almost disappeared.(3) EGFP+cells from monoclonal C12 cell lineage showed the malignant characteristics such as loss of contact inhibition, rapid proliferation andchromosome aneuploidy, as well as high tumorigenic rate in nude mice (5/5).They also expressed macrophage specific marker CD68 and showed a large number of telocentric chromosomes.Conclusion The results of this study suggested that the malignant transforma-tion of host macrophages as previously observed in solid tumor might be induced by cell fusion occurred be-tween human glioma cells and macrophages.Along with the previous evidences showing the isolation of the malignantly transformed macrophages ( ihCTC) from solid tumor tissue of tumor-bearing mice, the results confirmed an objective existence of malignant transformation of host macrophages in tumor microenvironment. The malignant transformation of host cells induced by fusion with tumor cells revealed not only a new under-standing for the progression of tumor and cancer heterogeneity, but also new targets for cancer therapy.

Objective A method for quantitative determination of 16 kinds of organochlorine pesticide (OCPs) in aquatic prod-ucts by gas chromatography (GC)was established .Methods The sample was extracted by acetonitrile ,purified by Carb/NH2 ,and then determined by GC .Results The linear relations of 16 kinds of OCPs were good at 0 .05 - 1 .00 mg/L(r> 0 .998) .The limit of detection of OCPs was in the range of 0 .04 - 0 .31 μg /kg(S/N = 3) .When the standard levels were 50 ,100 ,200 μg /kg ,the recovery rates were 72 .6% - 115 .2% ,the relative standard deviations were 0 .6% - 7 .5% .Conclusion The method established in this stud-y is applied to the determination of 16 kinds of OCPs in real samples with satisfactory results .

OBJECTIVE:To establish a method for simultaneous determination of the contents of Cu,Pb,As,Cr,Cd,Ba, Mn,Sb and Hg in Ganmaoling granule. METHODS:ICP-MS was conducted. The sample was handled by nitric acid microwave di-gestion system,the mass concnetration of 9 metal elements were determined by ICP-MS with Ge,In,Bi as internal standard and standard substance of test element standards. RF power was 1 100 W,sampling depth was 8 mm,carrier gas was argon(Ar)with high purity and flow rate was 1.0 L/min. RESULTS:All 9 elements had good linear range between mass concentration and ion peaks (r=0.999 1-0.999 9),detection limits were in the range of 0.3-6.0μg/L;RSDs of precision,stability and reproducibility tests were no more than 6.0%;average recoveries were in the range of 80.0%-113.5%,and RSDs were in 1.0%-4.5%. CONCLUSIONS:The method is simple,rapid and accurate,and can be used for the determination of 9 metal elements in Ganmaoling granule.

Objective Exploring theoretical teaching model of chronic diseases management of preventive medicine undergraduates,to provide feasible suggestions to improve the theoretical teaching of the chronic disease management ability of preventive medicine specialty in China so that graduates can better adapt to chronic diseases management work.Methods On the basis of reading a large number of relevant literature both at home and abroad,the research team designed questionnaires,and conducted a questionnaire survey on 190 respondents who engaged in chronic diseases management or teaching in central China.The content includes the understanding of the importance of training chronic disease management ability in undergraduate education of preventive medicine and the constitution and training mode of undergraduates' chronic disease management ability.EpiData 3.1 software was used to input survey data,SPSS 23.0 software was used for statistical description analysis,and the usage ratio and component ratio were used for statistical description analysis.Results The survey found that more than 50％ of the respondents believed that training students with chronic disease management should focus on prevention,intervention services and health promotion ability,and chronic disease modules need to be added to undergraduate courses in preventive medicine.Conclusions preventive medicine undergraduates need to be improved,and medical colleges should change teaching model to increase undergraduates' ability of chronic diseases management.