The PROFILE of assessment program for internal medicine internship of Sun Yat-Sen University.

Objective: To reflectively look at the present methods by which the clinical competence of 5th-year medical students (i.e. interns) in Sun Yat-Sen University (SYSU) are assessed upon finishing internship rotation in internal medicine (IM). Methods: Current procedures for the competence assessment of end-of-rotation IM interns in the First Affiliated Hospital of SYSU were reviewed, along with a point-by-point appraisal based on the PROFILE approach to structured assessment, and, whenever possible, suggestions for future improvement. Results and discussions: On a scale of 1-10, with 10 being the best or the most ideal, our marks for current methods to assess end-of-rotation IM interns in terms of being Programmatic, Real-World, Outcome-based, Formative, Impactful, Learner-engaged, and Evaluation-guaranteed were 7, 9, 3, 4, 6, 8, and 1, respectively. The strengths, weaknesses as well as potential solutions in each of the seven aspects are also discussed separately. Conclusions: Current assessment program for IM internship is strong in being programmatic, real-world, educationally impactful and learner engaged, and has room for further improvement in its time-based arrangements, relative shortage of feedback provision, as well as a systematic lack of quality control measures.

EYA4 functions as tumor suppressor gene and prognostic marker in pancreatic ductal adenocarcinoma through ß-catenin/ID2 pathway.

Eye absent homolog 4 (EYA4) was initially found as key gene in controlling eye development in Drosophila. We recently found that EYA4 was an independent prognostic factor in hepatocellular carcinoma. Its biological functions in malignancies remained unknown. The present study aimed at investigating its biological functions, molecular mechanisms and prognostic values in pancreatic ductal adenocarcinoma (PDAC). Overexpression of EYA4 in PDAC cells inhibited proliferation and invasion in vitro and tumor growth in vivo. Depletion of EYA4 in PDAC cells enhanced proliferation and invasion in vitro and tumor growth in vivo. Mechanistically, armed with the serine/threonine-specific protein phosphatase activity, EYA4 dephosphorylated ß-catenin at Ser675, blocked ß-catenin nuclear translocation and inhibited ID2 transactivation. Consistently, EYA4 expression inversely correlated with the levels of p-Ser675-ß-catenin and ID2 in tissues. EYA4 expression in PDAC tissues was significantly reduced as compared with adjacent non-tumoral tissues. EYA4 expression was an independent prognostic factor in PDAC, with a lower EYA4 level in association with shorter long-term survival and disease-free time. We showed that EYA4 functioned as tumor suppressor gene in PDAC via repressing ß-catenin/ID2 activation, and was an independent prognostic factor in PDAC.

DNA methylation profiling identifies EYA4 gene as a prognostic molecular marker in hepatocellular carcinoma.

BACKGROUND: DNA hypermethylation plays important roles in carcinogenesis by silencing key genes. This study aims to identify pivotal genes in hepatocellular carcinoma (HCC) by DNA methylation microarray and to assess their prognostic values. MATERIALS AND METHODS: DNA methylation microarray was performed in 45 pairs of HCC and adjacent nontumorous tissues and six normal liver tissues to identify hypermethylated genes in HCC. Potential prognosis-related genes were selected among hypermethylated genes by analyzing influences of methylation levels on disease-free survival (DFS) and overall survival (OS) in 45 patients. Their prognostic values were validated in 154 patients with HCC (including the initial 45 patients) to determine the independent prognostic gene. RESULTS: Altogether, 54 CpG islands in 44 genes were hypermethylated in HCC compared with liver tissues. Among them, methylation levels of ERG and HOXA11 were inversely associated with DFS (both P < 0.050), and methylation levels of EYA4 were inversely related to DFS and OS (both P < 0.050). EYA4 expression was inversely related to tumor size (P < 0.050). Lower EYA4 expression and larger tumor size were independent predictors of both shorter DFS and OS, and higher Barcelona Clinic Liver Cancer (BCLC) staging was an independent predictor of shorter OS (all P < 0.050). CONCLUSIONS: EYA4 functions as a prognostic molecular marker in HCC. Its aberrant hypermethylation and subsequent down-regulation may promote tumor progression.

Inhibition of Wnt signaling induces cell apoptosis and suppresses cell proliferation in cholangiocarcinoma cells.

The aim of the present study was to explore possible gene therapy for hilar cholangiocarcinoma by detecting the activation of the Wnt signaling pathway in 4 cholangiocarcinoma cell lines and inhibiting its expression by RNA interference (RNAi) targeting key factors of this pathway. The expression levels of the Wnt pathway-related factors, Wnt2, Wnt3, ß-catenin and transcription factor 4, and its target genes, c-myc and cyclin D1, in 4 cholangiocarcinoma cell lines were detected by RT-PCR, western blotting and immunofluorescence microscopy. After transfection of siRNAs targeting Wnt2 and ß-catenin into FRH0201 cells, the expression of the Wnt pathway-related factors and its target genes was again detected, and the cell cycle distribution, apoptosis and proliferation were analyzed by flow cytometry and MTT assay. Activation of the Wnt pathway and the expression of its target genes were detected in all 4 cell lines at various levels. After siRNA transfection, the expression of the target genes in the FRH0201 cells was significantly downregulated. In addition, the Wnt pathway was blocked, cell apoptosis was enhanced and cell proliferation was suppressed. In conclusion, the Wnt signaling pathway is activated in cholangiocarcinoma cells. RNAi technology targeting Wnt2 and ß-catenin may be a possible gene therapy for hilar cholangiocarcinoma.

Monoamine oxidase A expression is suppressed in human cholangiocarcinoma via coordinated epigenetic and IL-6-driven events.

The secretion of dopamine and serotonin is increased in cholangiocarcinoma, which has growth-promoting effects. Monoamine oxidase A (MAOA), the degradation enzyme of serotonin and dopamine, is suppressed in cholangiocarcinoma via an unknown mechanism. The aims of this study were to (i) correlate MAOA immunoreactivity with pathophysiological parameters of cholangiocarcinoma, (ii) determine the mechanism by which MAOA expression is suppressed and (iii) evaluate the consequences of restored MAOA expression in cholangiocarcinoma. MAOA expression was assessed in cholangiocarcinoma and nonmalignant controls. The control of MAOA expression by promoter hypermethylation was evaluated and the contribution of interleukin-6 (IL-6) signaling to the suppression of MAOA expression was determined. The effects of MAOA overexpression on cholangiocarcinoma growth and invasion were also assessed. MAOA expression is correlated with differentiation, invasion and survival in cholangiocarcinoma. The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. IL-6 signaling also decreased MAOA expression via a mechanism independent of hypermethylation, involving the regulation of the balance between SP-1 transcriptional activity and its inhibitor, R1 repressor. Inhibition of both IL-6 signaling and DNA methylation restored MAOA levels to those observed in cholangiocytes. Forced MAOA overexpression inhibited cholangiocarcinoma growth and invasion. MAOA expression is suppressed by the coordinated control of promoter hypermethylation and IL-6 signaling. MAOA may be a useful prognostic marker in the management of cholangiocarcinoma, and therapies designed to increase MAOA expression might prove beneficial in the treatment of cholangiocarcinoma.

Killing effects of different physical factors on extracorporeal HepG2 human hepatoma cells.

OBJECTIVE: To determine the killing effects on extracorporeal HepG2 cells under different temperatures, pressures of permeability and lengths of treatment time. METHOD: According to different temperatures, pressures of permeability and lengths of treating time, extracorporeal HepG2 cells of human hepatoma cell-line were grouped to 80 groups. Cell index (CI) as the measurement of killing effect were calculated by monotetrazolium (MTT) methods, i.e., CI = 1 - (the OD value in treated group - the OD value in blank control group)/(mean of untreated control group - mean of blank control group). According to the factorial design, data were fed into SPSS 10.0 and analyzed by three-way ANOVA (analysis of variance). RESULT: Temperature, pressure of permeability and length of treating time all had effects on the CI (cell index) level. Length of treating time was the most influential factor of the three. Additionally, any two of them all had statistically significant interactive effects on the CI level. When treated for 5-30 min, destilled water at 46 degrees C stably generated the highest CI. CONCLUSION: The "46 degrees C-destilled water-60 min" was considered as the optimal combination of conditions which lead to highest CI. We suggest exerting celiac lavage for 15 min with stilled water at 40 degrees C-43 degrees C in surgical practice as a hyperthermia treatment to achieve ideal killing effects on free cancer cells, which is feasible, practical, and clinically effective.

Application of ultrasonic to speciation analysis of heavy metals in soil.

In order to reduce the operation time and improve the extraction efficiency, ultrasonic energy by means of ultrasonic bath was used to the modified Tessier sequential extraction for speciation analysis of heavy metals in soil. Extractable contents of Cu, Fe, Mn, Ni, Pb and Zn were measured by atomic absorption spectroscopy (AAS). The merit of the ultrasonic extraction (UE) applied to the modified Tessier method is not only that the operation time for the first 4 fractions was reduced from ca. 18 h to 8 h, comparing with conventional extraction (CE), but also the extraction efficiency was higher. The results for both of UE and CE were consistent. The extractable Cu, Ni and Zn in the sample No. 1 were mainly associated with the third fraction (Fe-Mn oxides fraction), and fourth fraction (organic matter fraction) in the sample No.2. The extractable Fe and Mn were all mainly associated with the third fraction, and Pb the fourth fraction in both of the samples. The effects of concentration of hydroxylamine chloride on the capability for the extraction of studied metals were also studied.