Aim To investigate the anti-proliferative effect of salinomycin on doxorubicin-resistant human breast cancer MCF-7 /DOX cells.Methods MCF-7 and MCF-7 /DOX cells were treated or untreated with salinomycin.Cell viability was detected by MTS assay. Cell apoptosis was detected by Annexin V-FITC /PI as-say.Reactive oxygen species (ROS)was measured by DCFH-DA staining.Mitochondrial membrane potential was measured by JC-1 assay.The expression of apopto-sis related proteins BAX, BCL-2, caspase-3, and caspase-9 were evaluated by Western blot analysis. Results The cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. The flow cytometry results showed that salinomycin in-duced MCF-7 /DOX cell apoptosis,increased ROS pro-duction,and decreased mitochondrial membrane poten-tial.Furthermore,salinomycin decreased the expres-sion of BCL-2,and increased the expression of BAX, cleaved caspase-3,and cleaved caspase-9.Moreover, the antioxidant N-acetylcysteine (NAC ) markedly blocked the above effects.Conclusions Our results suggest that salinomycin-induced apoptosis in MCF-7 /DOX is associated with induction of ROS production, and activation of mitochondria apoptosis pathway, which may become a potential chemotherapeutic agent for the therapy of doxorubicin resistant breast cancer.

Objective To explore the effect and molecular mechanism of miR-34c in cell proliferation and invasion of human prostate cancer PC3 cells.Methods miR-34c was synthesized and transfected into prostate cancer PC3 cells.The ability of cell pro liferation was examined with methyl thiazolyl tetrazolium (MTT),and invasion with Transwell assay.The level of c-met mRNA was analyzed by real-time reversing transcription polymerase chain reaction (RT-PCR).Western blot was used to detect the expressions of cmet,cyclin D1,and EMT-associated markers.Results Over-expression of miR-34c reduced PC3 cell proliferation,and inhibited the abilities of invasion.Bioinformatics analysis showed that 3'-UTR of c-met had two miR-34c matched sites,and miR-34c inhibited the expressions of c-met mRNA and protein.Meantime,miR-34c obviously decreased the expressions of cyclin D1 and N-cadherin,but increased the expression of E-cadherin in PC3 cells.Conclusions miR-34c may suppress cell proliferation and invasion in prostate cancer PC3 cells,by which mechanism is related to reduction of the expressions of c-met,cyclin D1,N-cadherin,and upregulation of E-cadherin.

Objective To determine pharmacokinetics profiles of sodium alginate dexamethasone in perilymph after trans-round window administration of the sodium alginate dexamethasone gel in vivo.Methods 30 healthy guinea pig were randomly divided into 6 groups.Alg-Dex gel was placed into the niche of the round window of the guinea pig on the right ear.The perilymphetic samples were harvested on day 1,2,3,4 and 5 after administration of Alg-Dex gel respectively.The concentrations of dexamethasone in perilymph were assayed with high performance liquid chromatograph(HPLC).Results Concentrations of dexamethasone in perilymph on day 1,2,3,4 and 5 after administration of Alg-Dex gel were 0.49?0.06,1.32?0.28,0.65?0.08,0.66?0.05,0.53?0.17 mg/L respectively.Concentrations of dexamethasone in perilymph reached a peak on the second day and maintained 0.61?0.07 mg/L steadily on following days after administration.Conclusion Dexamethasone can be released from the sodium alginate dexamethasone gel persisitently and steadily in vivo.

Background Implantable contact lens (ICL) surgery is a primary intraocular refractive corrective surgery for high myopia.However,whether there will be enough distance between ICL and anterior face of lens to avoid the occurrence of anterior capsular cataract in non-accommodated and the largest physiological accommodated state after ICL implantation is worthy of investigation.Objective The purpose of this study was to investigate the alteration of lens vault after ICL implantation and explore the relationship between accommodation and change of lens vault.Methods A observational study was carried out.Sixty-six eyes of 33 patients with high myopia who received ICL implantation were enrolled in Affiliated First Hospital of Guiyang Medical College from May to November,2012.Best corrected visual acuity (BCVA),uncorrected visual acuity (UCVA),refractive diopter were regularly examined using synthetical optometry,and crystalline lens rise (CLR) and lens vault in non-accommodative or accommodative condition were observed by the anterior segment OCT (Visante OCT) and ultrasound biomicoscopy (UBM) before operation and 1 day,1 week,l month and 3 months after operation.Data were analyzed with SPSS version 16.0.Repeated measurement one-way analysis of variance was used to compare the differences of vision and refractive diopter among various time points.The relationship between accommodation and CLR was assessed using Pearson linear correlation.The alteration of CLR with accommodation change was analyzed by linear regression equation.Lens vault was measured and compared between non-accommodation and maximal physical accommodation status by paired t test.Results The postoperative UCVA was improved in comparison with preoperative BCVA,and the postoperative diopter was significantly lower than that of preoperation,with significant differences among various time points (F =16.904,P =0.000 ; F =1.498,P =0.000),and the diopter was stable after operation.A positive correlation was found between the alteration of CLR and accommodation under the physical accommodative stimulation in high myopic eyes (R2 =0.49,P =0.00).Under physiological accommodation,CLR elevated 20 μm for per 1.0 D accommodation.In addition,the difference of lens vault values within postoperative 3 months was statistically significant (F=16.025,P=0.000).The lens vault values lowed with the enlargement of accommodation in 48.5％ eyes,and the lens vault values increased with the enlargement of accommodation in 50.0％ eyes.However,1.5％ of the lens vault were in a stable state under the maximal physiological accommodated condition 3 months after operation.Lens vault were greater than zero in 97.0％ eyes (64/66),and only 3.0％ eyes (2/66) were zero under the maximalphysiological accommodated condition.Significant differences were seen in the lens vault between nonaccommodated and the maximal physiological accommodated state 1 day or 1 week after operation (t =4.755,P =0.000 ;t =3.327,P =0.001) ; but there was no statistical significance in 1 month or 3 months after operation (t =1.544,P=0.127,t=0.621,P=0.537).Conclusions During physiological accommodation,the alteration of CLR with accommodation in high myopic eyes.The location of ICL in the eyes is unstable within 3 months after operation.Majority of operative eyes remain enough vault in the maximal physiological accommodated state,but minority of operative eyes occur contact of ICL with the anterior surface of lens.Whether this contact causes anterior capsular cataract still needs to study.

It presented in detail the acquisition of Qingdao Wan Jie Hospital by the Affiliated Hospital of Medical College Qingdao University, describing the operational mechanisms in organizational setup, specialty setup, personnel management, logistic management, hospital culture and branding of the newly acquired section. It also summarized the achievements in medical resources reorganization and advantages complementary without government investment in a fast and low-cost manner. It is demonstrated that hospital acquisitions are in line with the medical reform, as they expand the service coverage of public hospitals, and extend medical service to the communities and lower levels, thus enhancing hospitals' impact and reach to integrate medical resources in a short timeframe.

Objective To explore the effect and molecular mechanism of N-myc downstream regulated gene 1 (NDRG1) on transforming growth factor-beta (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung cancer cells.Methods Lung cancer A549 cells were transfected with NDRG1 overexpressed vector,and then treated with 5 μg/L TGF-β1.The abilities of invasion were detected by Transwell assay.The expressions of NDRG1 mRNA and protein were analyzed by teal-time reverse transcription polymerase chain reaction (RT-PCR) were examined with Western blot.The expressions of EMT-associated markers E-cadherin and Vimentin,and EMT-associated signaling molecules Snail,AKT and Smad were detected with Western blot.Results We found that TGF-β1 treatment could induce morphological alteration of A549 cells from epithelial morphology to mesenchymal morphology.TGF-β1 significantly increased the migration of A549 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More importantly,overexpression of NDRG1 significandy reversed the effects of TGF-β1 on A549 cells.Moreover,NDRG1 significandy decreased the levels of phospho-AKT,and suppressed the expression of EMT-related transcription factor Snail.Conclusions NDRG1 could reverse the effects of TGF-β1 on EMT in A549 cells,by which mechanism is related to reduction of the expressions of phospho-AKT and Snail.

Objective To observe the clinical efficacy and adverse reactions of intensity modulated radiotherapy (IMRT) combined with cisplatin for patients with carcinoma of cervix.Methods One hundred patients with carcinoma of cervix were randomly divided into 2 equal groups to undergo IMRT only (IMRT group)and IMRT combined group (IMRT with cisplatin chemotherapy group),with 50 cases in each.Both groups were treated with external intensity modulated radiotherapy,with the total dose of 50 Gy,2 Gy/fraetion,25 fractions in total,and 5 times/week.Two weeks later,internal radiotherapy followed,with the total dose of 42-48 Gy,1 time/week with 6-8 times and 6-7 Gy/fraction.When the internal radiotherapy began,the external radiotherapy stopped immediately.The combination group was treated concurrently with cisplatin given by intravenous drip once a week,at the dose of 30-40 mg/m2 body surface area for 4-5 weeks,and with total cisplatin dosage of 50-65 mg.Follow-up was conducted for 18 months(3-60 months).The 1-,3-,and 5-year survival rates,local control rate,distant metastasis rate,and disease-free survival rate,blood test,rectum,and bladder were observed.Results The 1-year survival rate,local control rate,distant metastasis rate,and disease-free survival rate did not differ significantly between these 2 groups,however,the 3-and 5-year survival rates,local control rates,distant metastasis rates and disease-free survival rates of the combination group were all significantly better than those of the IMRT group (x2 =3.843,4.336,4.336,4.960,P ＜ 0.05 ; x2 =3.934,4.454,4.000,4.244,P ＜0.05).The incidence rates of radiation proctitis and leukopenia of the combination group were significantly higher than those of the IMRT only group (x2 =4.110,4.320,P ＜ 0.05),whereas the incidence rates of cystitis,anemia,and thrombocytopenia were not significantly different between these 2 groups.No serious grade 3-4 proctitis and cystitis were observed in these 2 groups.Conclusions The IMRT combined with cisplatin chemotherapy shows higher 3-year and 5-year long-term efficacy in the patients with carcinoma of cervix than IMRT only group.

Objective To explore skeletal‐related events (SREs) clinical factors and analysis prognosis factors on patients with non‐small cell lung cancer(NSCLC) with bone metastases .Methods We collected clinical data of pathology confirmed 383 patients with non‐small cell lung cancer between April 2007 and January 2007 in the third affiliated hospital of the third military medical uni‐versity .It was used to screening for Emission Computed Tomography (ECT ) for bone metastases .And then it was need to con‐firmed for CT ,MRI or PET‐CT or pathology .Statistics in patients between clinical features and the SREs prediction factor with Univariate and Multivariate .And Kaplan‐Meier method analysis of survival in the non‐small cell lung cancer patients with bone me‐tastases .Results Out of 383 patients with bone metastases ,178 patients with SREs .The incidence was 46 .5% .Univariate analysis showed that women ,adenocarcinoma ,never smoking history ,single bone metastases ,bisphosphonate therapy ,targeted therapy in patients with bone metastases are less likely to have SREs ,it was considered statistically significant (P<0 .05) .Multivariate analy‐sis showed multiple bone metastases and no bisphosphonate therapy is independent risk factors for SREs .Median survival time was 14 .5 months in non‐small cell lung cancer patients with bone metastases ,1 year survival rate was 46 .5% ,2 years survival rate was 15 .9% .The survival analysis shows that more bisphosphonate treatment and bisphosphonate with EGFR‐TKI therapy on the prog‐nosis of patients with statistically significance (P<0 .05) .Conclusion It was likely to occur SREs in NSCLC patients with bone metastases .No bisphosphonate and multiple bone metastases are independent risk factors for SREs .Bisphosphonate treatment may prevent or reduce occur SREs for NSCLC patients with bone metastases ,and it may prolong survival ,it speculated that bisphospho‐nate may have resistant NSCLC cell activity .

The self-microemulsion formulation of potassium dehydroandrographolidi succinas (PDS) has been optimized and the performance in vitro has been evaluated preliminary. Kinds of prescription accessories were screened by solubility based on the emulsifying result and efficiency, particle size of emulsions. The optimal formulation composition and compatibility proportion were determined by orthogonal design and pseudo-ternary phase diagrams. The appearance, particle size, Zeta potential and stability of this formulation were also investigated. The optimized prescription of PDS was 10% MCT, 40% Tween-20 and 50% glycerol. It can spontaneously form a transparent pale blue opalescent emulsion with emulsification time 31.27 s, particle size 37.1 nm, Zata potential -17.4 mV and good stability.

Objective To explore the effect and molecular mechanism of HDAC inhibitor SNDX-275 inhibiting cell proliferation in ErbB2-overexpressing breast cancer BT474 cells.Methods Breast cancer BT474 cells were treated with HDAC inhibitor SNDX-275,setting as test group,and the cell line treated with phosphate buffered saline (PBS)as control.The concentration of SNDX-275 were 0,0.5,1 .0,2.0,3.0,4.0 μmol/L respectively.Cell proliferation was analyzed by MTS assay and colony formation assay,the expressions of ErbB2, ErbB3,p-Akt were analyzed by Western blotting,and the expressions of miR-125a,miR-125b were analyzed by RT-PCR.After transfecting miRNA125 inhibitor into BT474 cells,the inhibition rate of SNDX-275 was tested by MTS assay .Results MTS result showed that SNDX-275 inhibited cell proliferation in BT474 cells in a dose-dependent manner.The inhibition rate of 4.0 μmol/L SNDX-275 was about (68.00 ±4.45)%.Clone assay indicated SNDX-275 could inhibit the proliferation of BT474 cells.Western blotting result indicated that SNDX-275 significantly inhibited the protein expressions of ErbB2,ErbB3 and p-Akt,RT-PCR result illustrated 2 μmol/L SNDX-275 could increase the expressions of miR-125a and miR-125b about 3.22 ±1 .17,5.42 ±0.38 times compared with the PBS control respectively,the difference has a statistical significance (t =4.338,P =0.049;t =21 .805,P =0.002).MTS result indicated that compared with the PBS control,the inhibition rate of SNDX-275 group was (56.97 ±3.56)%,while the inhibition rate of SNDX-275 and miRNA125 inhibitor group
was (10.67 ±2.21 )%,with a statistical significance(t =-10.993,P =0.008).Conclusion SNDX-275 could inhibit cell proliferation of ErbB2-overexpressing breast cancer BT474 cells,by inhibiting ErbB2-ErbB3-Akt sig-nal pathway through up-regulating miR-125a and miR-125b.