AIM:To investigate the effect of case-based learning ( CBL) teaching combination with paper review method in the teaching of ophthalmology residents. ·METHODS:The study was conducted from 2015 to 2016. The residents in Department of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital were included in the research. During the year of 2015, the traditional lecture-based learning ( LBL) method was applied (as a control group). During the year of 2016, the CBL teaching combination with paper review teaching method was applied (as an experimental group). At the end of the course, exams and questionnaires were conducted to evaluate the teaching effect of two different methods. The exams consisted of theoretical and operational assessment. The teaching satisfactions, learning interests, scientific research interests and clinical abilities were included in the questionnaires. The data was analyzed by SPSS 16. 0. ·RESULTS:The results of final exams indicated that the scores of the experimental group (88. 2±6. 5) were higher than the control group ( 75. 6 ± 6. 0 ). The difference showed statistically significant (t=6. 68, P<0. 05). The results of questionnaires indicated that students showed much more satisfied with CBL teaching combination with paper review teaching method ( 91%) than traditional teaching method (50%, x2 =8. 84, P<0. 05). Students in the experimental group improved learning interest ( x2 =6. 29, P<0. 05), increased research interest (x2=4. 54, P<0.05) and approved clinical ability (x2 =4. 25, P<0. 05). The comparison of two groups showed the statistically difference (P<0. 05). ·CONCLUSION: CBL teaching combination with paper review teaching method is beneficial to improve the teaching effect, and it is also beneficial to train residents'clinical skills and research abilities.

Objective To evaluate the safety,biocompatibility and efficacy of transcatheter closure of atrial septal defect(ASD)with no stainless-steel-screw occluder in canine model.Methods The device was constructed from superelastic Nitinol wires tightly woven into two flat disks and sewed with polyester fibers inside,with a pliable loop on the right-atrial-disk of the device,connecting to the delivery cable.ASD was created by transcatheter puncture and balloon dilatation and then closed by occluder under fluoroscopy in the catheterization laboratory.The location and the influence of the implanted device on function of tricuspid valve and mitral valve were evaluated by echocardiography.At 1,2,3 and 6 months after the operation,the animals were killed and autopsy was conducted.Results Eight dogs with puncture-produced ASD underwent ASD closing procedure successfully.The occluder showed no influence on the function of MV and AV demonstrated by echocardiogram.The two disks of the implanted device were covered with a smooth intact neogenesis layer in all dogs.Endocardial cells fully covered the surface of the two disk without inflammating reaction 3 months later. There was no evidence of corrosion on the surface of the nitinol wire removed from the dog after 6 months.Light microscopic examination of the liver,kidney,lung and spleen showed no evidence of embolization and inflammation.Conclusion Transcatheter ASD occlusion with new-type occluder is safe,feasible,effective and good biocompatibility with a good prospective clinical application.

Objective To explore the pathological and imaging features of epithelioid angiomyolipoma(EAML). Methods A 47-year-old man presented with dull pain in left upper abdomen for 1 year admitted to hospital.Accompanied with several enlarged lymph nodes,a mass with the largest diameter of 28 cm in the left kidney was inhomogeneously enhanced on CT.The left kidney and the mass were radically resected with regional lymph node dissection after general anaesthesia. Results During the operation,a well-circumscribed,encapsulated mass with several paraaortic lymph nodes was found on the upper-middle left kidney.The gross cut surface showed fleshy texture with regions of necrosis.Microscopically and immunohistochemistrically,diffuse sheets of epithelioid cells were found with positivity for HMB-45 and negativity for EMA.CT features included higher pre-contrasted density,absent fat,enhanced mode of quick wash-in and slow wash-out.There was neither metastasis nor recurrence during the 1 year follow-up. Conclusion EAML with malignant potency is a rare tumor of mesenchymal tissue presenting with some specific radiopathological features and a good prognosis.

Objective To investigate the clinical significance of contrast-enhanced transrectal ultrasound(CE-TRUS) in the perineal prostate biopsy. Methods A total of 116 patients was undergone prostate biopsy through the perineum under the direction of tansrectal ultrasound. Prostate biopsy standard was based on 2007 CUA revised guidelines for diagnosis and treatment of urological diseases.Color Doppler ultrasonography was used to check the prostate and to learn the prostate focal lesion,size, number and echo color Doppler flow characteristics. Of the 116 cases, 43 patients was undergone contrast-enhanced transrectal ultrasound. Results The biopsy results confirmed the diagnosis of prostate cancer was 64 cases, Benign prostatic hyperplasia was 52 cases. Of 43 cases who undergone contrast-enhanced transrectal ultrasound, Prostate cancer and Benign prostatic hyperplasia were 25 and 18 cases, respectively. CE-TRUS group and TRUS group showed no statistical difference between two groups. Analyzed the cases with PSA≤30 ng/ml, CE-TRUS group had a higher positive rate of biopsy (P=0.046). Conclusion TRUS guided transperineal biopsy of prostate might be an method for the diagnosis of prostate cancer with a higher accuracy rate. CE-TRUS can improve the biopsy positive rate of prostate cancer.

Objective To analyze gene expression profiles of biopsy specimens from breast cancer patients who were treated with neoadjuvant chemotherapy(NAC) after biopsies, and to identify the genes which are closely associated with the efficacy of neoadjuvant chemotherapy with T/FAC [docetaxel(Taxotere), 5-fluorouracil, doxorubicin and cyclophosphamide] or T/FEC (Taxotere, 5-fluorouracil, epirubicin and cyclophosphamide) regimen.Methods We retrieved and collected gene expression profiles from publicly available databases.Four datasets, a total of 844 samples, were finally retained because all the patients had received a uniform neoadjuvant chemotherapy regimen.Response to neoadjuvant chemotherapy was categorized as a pathological complete response (pCR) or residual invasive cancer (RD).The differentially expressed genes (adjusted P-value<0.05) and therapeutic efficacy were analyzed and explored.Results After differential analysis, genes whose expressions were higher or lower in pCR group than in RD group were identified in each of the four datasets, respectively.There were 34 and 42 genes which were simultaneously more highly expressed or more lowly expressed in pCR group than in RD group in the four datasets.The unsupervised clustering, based on the 76 intersection genes, showed that the pCR specimens tended to form one cluster and the RD tended to form the other.Conclusion The seventy-six differentially expressed genes are associated with the efficacy of neoadjuvant chemotherapy and are likely to be novel predictive biomarkers for the efficacy of neoadjuvant chemotherapy.

AIMTo investigate the cellular uptake of monostearin solid lipid nanoparticles (MSLN) and the influence on the cellular uptake by MSLN modified with PEG2000 in human-type II cell alveolar epithelial cell line (A549) and murine macrophages cell line (J774A1).

METHODSMSLN were prepared by a novel solvent diffusion method. The particle size distribution and zeta potential of MSLN, measured by light scattering and electrophoretic mobility, were investigated. The cytotoxicity of MSLN and MTX-loaded MSLN in A549 cells were performed by the MTT method. Rhodamine B was incorporated into solid lipid nanoparticles as fluorescent marker, after PEG2000 integrating monostearin during preparation, the cellular uptake of MSLN by A549 and J774A1 cell lines were determined spectrofluorimetrically.

RESULTSThe IC50 of MSLN and MTX-loaded MSLN on A549 cells were 227.56 microg x mL(-1) and 71.37 microg x mL(-1), respectively. The percentage of cellular uptake showed a negative correlation to the concentration of MSLN in incubation medium and the internalization behaved rapidly. Contrary to situation in J774A1 cell line, internalization of solid lipid nanoparticles was promoted with increasing the content of PEG2000 incorporated into MSLN in A549 cell line.

CONCLUSIONAfter modifying MSLN with PEG2000, it represents relative lower phagocytosis by J774A1 cell line and higher uptake in A549 cell line.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Cell Line ; Cell Line, Tumor ; Cell Survival ; drug effects ; Drug Carriers ; Drug Delivery Systems ; Glycerides ; chemistry ; metabolism ; toxicity ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Macrophages ; cytology ; Mice ; Nanotechnology ; Particle Size ; Phagocytosis

OBJECTIVE To explored the potential of pharmacological stabilization and reactivation of p53 for targeted cancer therapies. METHODS The cytotoxicity of a potent Cyclophilin A (CypA) inhibitor HL001 was tasted against a panel of cancer cell lines. The genotypes and activation of p53 were compared with the cytotoxicity profile of HL001. Two-dimensional (2D) PAGE analysis was performed to investigate differentially expressed proteins that involves in the anti-proliferation effects of HL001. Pull-down and Co-IP were used to confirmed the new identified PPI between CypA and G3BP1 and orthotopic animal model of lung cancer was used to tested the anti- tumor activity of HL001 in vivo. RESULTS We identify a novel CypA small molecule inhibitor HL001 that induces non-small cell lung cancer (NSCLC) cell cycle arrest and apoptosis via restoring p53 expression. We find that HL001 stabilizes p53 through inhibiting the MDM2-mediated p53 ubiquitination. Further mechanistic studies reveal that the downregulation of G3BP1 and the induction of reactive oxygen species and DNA damage by HL001 contribute to p53 stabilization. Surprisingly, HL001 selectively suppresses tumor growth in p53 wildtype NSCLC harboring Arg72 homozygous alleles (p53- 72R) through disrupting interaction between MDM2 and p53-72R in a CypA dependent manner. Moreover, combining HL001 with cisplatin synergistically enhance tumor regression in orthotopic NSCLC mouse model. CONCLUSION Pharma?cologic inhibition of CypA offers a potential therapeutic strategy via specific activation of p53-72R in NSCLC.

Objective To search for the metabolites that associated with articular cartilage damage in the urine of rat model with articular cartilage destruction induced by T-2 toxin.Methods Thirty healthy male Wistar rats aged 4-5 weeks were numbered by weight,randomly divided into two groups (n =15 per group),namely the control group and the model group.The rats in the control group were fed with standard rat diets,and those in the model group were given diets contaminated by T-2-toxin (300 μg/kg).Throughout the experiment,all animals were given free access to distilled water and diets.After continuous treatment for 3 months,all the rats were sacrificed.The changes of articular cartilage in rat knee joints were observed by histopathological method,the metabolic profile of rats' urine was determined by ultra performance liquid chromatography/quadrupole time of flight-mass spectrometry (UPLC/QTOF-MS) technique.Combined with multivariate statistical analysis,database searching was applied to explore and confirm the different metabolites associated with cartilage damage.Results Light microscope showed that rats' articular chondrocytes in the control group presented cells in neat rows and eumorphism,rats' articular chondrocytes in the model group presented extensive areas of chondrocyte degeneration,necrosis and loss.In rats' urine metabolic profiles,5 different metabolites associated with cartilage destruction were detected,such as 4-hydroxynonenal (HNE),trans-4,5-epoxy-2(E)-decenal (EDE),5-methyldeoxycytidine,and 5-L-glutamyl-glycine and prolyl-valine.Compared with the control group (mass spectrum peak area:65820 ± 5200,22080 ± 3538,4292 ± 3520,3277 ± 2025,1104 ± 990),all of them increased in the model group (mass speetrum peak area:90240 ± 18863,25610 ± 5071,9702 ± 6562,6029 ± 3905,4144 ± 5322,t =-3.903,-2.209,-2.814,-2.424,-2.174,all P ＜ 0.05).Conclusions The articular cartilage destruction induced by T-2 toxin could cause the changes of related metabolites in the urine;the 5 kinds of changed metabolites in urine are related to articular cartilage destruction.

Objective To study the correlation between the coagulation factor Ⅶ (F Ⅶ) and progressive hemorrhage after brain contusion in mice and provide the experimental evidence for the clinical application of recombinant human FⅦa.Methods Twelve male BALB/c mice were given liposomeencapsulated FⅦsiRNA via tail vein at doses of 1,3,5 and 10 mg/kg with 3 mice per dosage.The other 3 mice received equivalent volume of normal saline as controls.Two days after the injection,mice blood sampling was used to detect FⅦ mRNA expression in liver using real-time PCR,level of plasma FⅦ using ELISA method,and activity of plasma FⅦ using chromogenic substrate assay.The optimal dose at which F Ⅶ expression was inhibited was determined.Thirty BALB/c male mice were assigned to two groups (n =15 per group) according to the random number table:FⅦ-suppressing group,mice were injected with FⅦsiRNA at the optimal dose and control group,mice were injected with same volume of negative control vector.The model of brain contusion was established in both groups.Volume of hemorrhage following brain contusion was measured at 3,24 and 72 h postinjury,and hematoma volume at 24 and 48 h postinjury.Results Liposome-encapsulated siRNA delivery down-regulated FⅦ expression in the mouse liver.Level and activity of plasma FⅦ were also reduced significantly.The optimal siRNA dose was 3 mg/kg.At 3,24 and 72 h postinjury,relative volume of brain hemorrhage in FⅦ-suppressing group was 1.46 ± 0.10,1.82 ± 0.23 and 2.28 ± 0.15 respectively,significantly higher than that in control group (1.00 ± 0.25,1.20 ± 0.31 and 1.20 ± 0.22 respectively) (P ＜ 0.05).At 24 and 48 h postinju-ry,volume of hematoma in FⅦ-suppressing group was (6.7 ± 1.5)mm3 and (9.8 ± 1.0) mm3,significantly higher than that in control group [(5.2 ± 1.2) mm3 and (5.5 ± 1.5) mm3] (P ＜0.01).Conclusions Level of FⅦ in vivo relates closely to the progressive hemorrhage of brain contusion in mice.Administration of FⅦ is effective to reduce the incidence of progressive hemorrhage.

Objective To study the role of Med19 in bladder cancer by analyzing the effects of lentivirus-mediated suppression of Med19 expression on T24 bladder cancer cells in vitro.Methods The lentivirus vectors containing a small hairpin RNA (shRNA) to target Med19 were constructed.After T24 bladder cancer cells were infected,real-time PCR and Western-blotting were used to study the Med19 expressions in the CON group (non-infected cells),the NC group (Lv-NC-infected cells) and the KD group (Lv-shMed19-infected cells).The influence of Med19 on the proliferation of bladder cancer cells were assessed using MTT,BrdU,colony formation assay and tumorigenicity experiment in mice.Cell cycle was analyzed with flow cytometry assay.Results Med19 relative mRNA level (0.35 ± 0.03) and Med19 protein expressing in the KD group were significantly inhibited (P ＜ 0.05).The KD group displayed an increased proportion of cells (77.50 ± 0.29)％ in the G0/G1 phase compared with the CON group (69.81 ± 0.81)％and NC group (67.53 ± 0.67) ％ (P ＜ 0.05).Compared with the CON group and the NC group,the KD group displayed a significant cell proliferation defect by MTT and BrdU assay and the number of colonies (91.33 ± 6.11) was significant decreased (P ＜ 0.05).On the day 24,the tumor volume (596.64 ± 485.36) mm3 and weight (0.57 ± 0.44) g of the KD group mice were decreased after inoculation into nude mice (P ＜ 0.05).Specific lentivirus-mediated knockdown of Med19 significantly impacted the cell cycle and proliferation of bladder cancer cells.Infected T24 cells nearly lost their tumorigenicity when being inoculated into nude mice.Conclusion Our results provide new evidence of an important role for Med19 in the development of bladder cancer,suggesting that lentiviruses delivering shRNA against Med19 may be a promising tool for bladder cancer therapy.