Objective To investigate the role of autophagy in radiation-induced death response of human nasopharyngeal carcinoma cells.Methods MTT method was used to detect cell viability of CNE-2 cells in different time after irradiation.Clonogenic survival assay was used to evaluate the effect of autophagy inhibitor (chloroquine phosphate) and autophagy inductor (rapamycin) on radiosensitivity of nasopharyngeal carcinoma cells.Cell apoptosis was assessed by flow cytometry.The expressions of LC3 and P62 were measured with Western blot.Cell ultrastructural analysis was performed under an electron microscope.Results Irradiation with 10 Gy induced a massive accumulation of autophagosomes accompanied with up-regulation of LC3-Ⅱ expression in CNE-2 cells.Compared with radiation alone,chloroquine phosphate (CDP) enhanced radiosensitivity significantly by decreasing cell viability (F =25.88,P ＜ 0.05),autophagic ratio (F =105.15,P ＜ 0.05),and LC3-Ⅱ protein level(F =231.68,P ＜0.05),while up-regulating the expression of P62 (F =117.52,P ＜ 0.05).Inhibition of autophagy increased radiation-induced apoptosis (F =143.72,P ＜ 0.05).Rapamycin (RAPA) also significantly decreased cell viability,but increased autophagic ratio and LC3-Ⅱ protein level while down-regulated the expression of P62.Induction of autophagy increased radiation-induced apoptosis(F =167.32,P ＜ 0.05).Conclusions Blockage of autophagy with CDP could enhance radiosensitivity in human nasopharyngeal carcinoma cells,suggesting that inhibition of autophagy could be used as an adjuvant treatment to nasopharyngeal carcinoma.

Objective To study the difference of gene expression profile between the radioresistant human nasopharyngeal carcinoma cell line CNE-2R and CNE-2,and to screen the signaling pathway associated with radioresistance of nasopharyngeal carcinoma.Methods The radioresistant nasopharyngeal carcinoma cell line CNE-2R was constructed from the original cell line CNE-2.CNE-2R and CNE-2 cells were cultured and administered with 60Co γ-ray irradiation at the dose of 400 cGy for 15 times.Human-6v 3.0 whole genome expression profile was used to screen the differentially expressed genes.Bioinformatic analysis was used to identify the pathways related to radioresistance.Results The number of the differentially expressed genes that were found in these 2 experiments was 374.The Kegg pathway and Biocarta pathway analysis of the differentially expressed genes showed the biological importance of Toll-like receptor signaling pathway and IL-1 R-mediated signal transduction pathway to the radioresistance of the CNE-2R cells and the significant differences of 13 genes in these 2 pathways,including JUN,MYD88,CCL5,CXCL10,STAT1,LY96,FOS,CCL3,IL-6,IL-8,IL-1α,IL-1B,and IRAK2(t=13.47-66.57,P<0.05).Conclusions Toll-like receptor signaling pathway and IL-1R-mediated signal transduction pathway might be related to the occurrence of radioresistance.

Objective: This study aims to evaluate the prevention effect and cost-effectiveness of a prophylactic bivalent human papilloma virus (HPV) vaccine. Methods: A multiple health status dynamic model was developed, including natural history of diseases and prevention strategies. We built 19 prevention strategies including visual inspection with acetic acid/lugol's iodine (VIA/VILI) and/or 3 does prophylactic bivalent HPV vaccine administered to adolescent girls at the age of 15 years old every year under the assumption that vaccine coverage and screening coverage were 70%. The incremental cost-effectiveness ratio (ICER), optimal price of 3 does vaccine and cost-effectiveness frontier of these strategies were analyzed compared with no-intervention. The ICER threshold is 152 087 CNY. Results: Compared with no-intervention, Routine vaccination reduced the incidence of cervical cancer by 69.5%, superior to 5 strategies including VIA/VILI screening only. The range of effect was between 9.0% and 69.2%, and the effect of strategy increased significantly with the increase of screening frequency. Combination vaccination with screening at ages of 35 reduced the incidence of cervical cancer by 72.0%, and the effect increased with the increase of screening frequency. Combination vaccination with screening every 3 years between (35-64) years old reduced the incidence by 89.4%. Compared with no-intervention, the ICER of combination vaccination with screening twice between 35 years and 64 years was 121 292 CNY/life-year, which was cost-effective. The price of vaccine had a significant impact on the ICER of the strategy; when the vaccine price was less than 600 CNY, only routine vaccination or supplementary vaccination between 16-39 years old after routine vaccination was cost-effective; when the vaccine price was less than 1 200 CNY, supplementary vaccination between 16-19 years old plus VIA/VILI was cost-effective. Conclusion Ther prevention strategy was cost-effective, which could effectively reduce the incidence of cervical cancer by implementation of HPV vaccination combined with VIA/VILI in suitable aging females.

Objective To discover radioresistance-associated proteins by performing comparative proteomic analysis on nasopharyngeal carcinoma cell lines.Methods The total proteins were extracted from radioresistant human nasopharyngeal carcinoma cell line CNE-2R and its parental cell line CNE-2,respectively.These proteins were separated by high quality two-dimensional polyacrylamide gel electrophoresis (2-DE) and then the 2-DE profiles were screened for differentially expressed protein spots by the Image Master 5.0 software.Those spots were identified by a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry.Results 32 significantly differentially expressed protein spots were screened in two different radiosensitivity cell lines and 11 proteins were identified by tandem mass spectrometry,among which 3 proteins were up-regulated in radioresistant human nasopharyngcal carcinoma cell line CNE-2R and the other 8 proteins were down-regulated.Conclusions The differentially expressed proteins of nasopharyegeal carcinoma cells with different radiosensitivity were mainly involved in apoptosis regulation,DNA damage and repair,cell cycle regulation,RNA transcription,cell signaling,cytoskeleton formation and radiation stress responses.

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Wuzhuyu Tang is a classical formula for treating migraine, but its' pharmacological ingredients is unclear yet. Present study employed the everted intestinal sac model to collect the absorption samples of 10 kinds of Wuzhuyu decoction, and then analyzed the contents of 9 ingredients in Wuzhuyu Tang and absorption samples quantitatively or semi-quantitatively by HPLC-DAD method. Reserpine was used to establish the mice model of migraine, and then the contents and activities of 5-hydroxytryptamine, noradrenaline, dopamine, nitric oxide and nitricoxide synthase in brain tissues and serums were determined respectively after oral administration of Wuzhuyu Tang. Using the partial least squares regression method to correlate the total absorption quantity of 9 ingredients and pharmacodynamics. The result shows that limocitrin-3-O-beta-D-glucoside, ginsenoside Rg1 and Rb1, rutaevine, limonin, evodiamine and rutaecarpine are the main ingredients influenced the effects in absorption samples in everted intestinal sacs, especially ginsenoside Rg1, rutaevine, evodiamine and rutaecarpine among them have obvious improving effects to most pharmacodynamics index, might be the pharmacological ingredients influenced the therapeutical effects of Wuzhuyu Tang treating migraine.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; Male ; Mice ; Mice, Inbred ICR ; Migraine Disorders ; drug therapy ; Rats ; Rats, Wistar

OBJECTIVETo investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype.

METHODSClinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated.

RESULTSPHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000).

CONCLUSIONSMissense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.

Adolescent ; Child ; Child, Preschool ; Familial Hypophosphatemic Rickets ; genetics ; Female ; Humans ; Infant ; Male ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Retrospective Studies

OBJECTIVETo investigate the effects of Salvianolic-acid B on p38MAPK signaling pathway and its transcriptional factor activated by Transforming growth factor b1 in rat hepatic stellate cells.

METHODSHepatic stellate cells were isolated from normal rat by in situ perfusion and Nycodenz density-gradient centrifugation method.TGFb1 (10 ng/ml), PD98059(50 mumol/L), SB203580(10 mumol/L) and SA-B (10-6 mol/L) were directly added to the medium of the isolated HSCs. Groups: (1)The detection of total p38, MKK3/6, MEF2A and MEF2C induced by TGFb1 in HSC: include control group, SA-B group, SA-B+TGFb1 group and TGFb1 group. (2)The detection of the phosphorylation of p38, MKK3/6 and a-SMA induced by TGFb1 in HSC: include control group, SA-B group, SA-B+TGFb1 group, TGFb1 group, PD98059 group, PD98059+SA-B group, PD98059+TGFb1 group and SA-B+PD98059+TGFb1 group. (3)The effects of SA-B on activity of MEF2 reporter and collagen a 1(I) reporter induced by TGFb1 in HSC: include mt group, wt group, TGFb1 group, SA-B+TGFb1 group, SA-B group, SB203580+TGFb1 group and SB203580 group. Total and phosphorylated p38 and MKK3/6, MEF2A, MEF2C and a-SMA were assayed by Western blot. HSCs were transfected with either MEF2 or collagen a1(I) luciferase reporter gene by Lipofectamine 2000 transfection method, Cellular extracts were assayed for both MEF2 and collagen a1(I) luciferase activities. Comparisons between groups were performed with Student-Newman-Keuls test.

RESULTSThe relative expression level of the phosphorylation of p38 of SA-B group is 0.33+/-0.05,obviously lower than control group(q=7.08, P less than 0.01); SA-B+TGFb1 group is 0.46+/-0.04, obviously lower than TGF b1 group(q=10.45, P less than 0.01); The relative expression level of the phosphorylation of MKK3/6 of SA-B group is 0.11+/-0.07, obviously lower than control group(q=3.944, P less than 0.05); SA-B+TGF b1 group is 0.28+/-0.07, obviously lower than TGFb1 group (q=7.91, P less than 0.01); The relative luciferase activity of MEF2 reporter of SA-B+TGFb1 group and SB203580+TGF b1 group is 2.93+/-0.09 and 2.50+/-0.05 respectively, both obviously lower than TGFb1 group(q=35.35 and 37.2, P less than 0.01); The relative expression level of MEF2C and MEF2A of SA-B group is 15.82+/-0.97 and 13.00+/-0.40 respectively, obviously lower than control group(q is 5.18 and 13.32, both P less than 0.01); SA-B+TGF b1 group is 13.40+/-0.72 and 20.47+/-0.83 respectively, obviously lower than TGFb1 group(q is 43.93 and 12.52,both P less than 0.01); The relative expression level of a-SMA of SA-B+TGFb1 group is 8.76+/-0.44, obviously lower than TGFb1 group(q=20.35, P less than 0.01); SA-B+SB203580+TGFb1 group is only 3.57+/-0.49, obviously lower than TGFb1 group(q=39.78, P less than 0.01); The relative luciferase activity of collagen a1(I) reporter of SA-B+TGF b1 group and SB203580+TGFb1 group is 1.61+/-0.05 and 1.42+/-0.07 respectively, obviously lower than TGFb1 group(q=26.4 and 27.62, both P less than 0.01).

CONCLUSIONSA-B could inhibit activation of HSC induced by TGFb1 through inhibiting p38MAPK signaling pathway in hepatic stellate cells.

Animals ; Benzofurans ; pharmacology ; Cells, Cultured ; Hepatic Stellate Cells ; drug effects ; metabolism ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

Cervical carcinoma has brought huge burden on patients, especially in developing countries. Preventive vaccines could effectively reduce the incidence of cervical carcinoma. The high prices were one of the most difficult problem in introducing the vaccine in developing countries, so the cost-effectiveness and health financing of the vaccines should be carefully studied before incorporated into the national immunization program. Thus, researchers used mathematical models to predict the effects of HPV vaccines and to study the cost- effectiveness. In order to understand the current situation on the cost-effectiveness of HPV vaccines in the developing countries, a systematic searching of literature from PubMed, Elsevier Science Direct, Medline, ProQuest, CNKI and Wangfang Data was performed, this study aims to conduct a systematic review from aspects of project source, first author, research areas, research perspectives, prevention strategies, vaccine characteristics, cost-effectiveness.
Cost-Benefit Analysis ; Developing Countries ; Female ; Humans ; Immunization Programs ; Incidence ; Models, Theoretical ; Papillomavirus Infections ; economics ; prevention & control ; Papillomavirus Vaccines ; economics ; Uterine Cervical Neoplasms ; economics ; prevention & control

As one of the primary prevention measures to reduce birth defects , the premarital healthcare service has played an important role in the prevention of communicable diseases , maintaining the harmonious and happy mar-riage, health and other aspects of protection of the next generation .Different countries and regions also design and implement the premarital medical examination system based on their actual situations .This article summarized the practices, characteristics and experiences of premarital healthcare services in some foreign countries and regions through several aspects including model , set projects content , financing and other aspects of the application of the premarital results.Finally, this paper put forwards suggestions on the premarital healthcare services in our country to help healthy the carrying out of the premarital work .