Objective:To investigate mechanisms whereby phospholipase D1(PLD1)promotes pancreatic ductal adenocarcinoma(PDAC)progression.Methods:Targets were identified by screening the Genomic Spatial Event(GSE)database for genes differentially expressed in metastatic and primary tumors.Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas.Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining.The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data.The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1.The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice.Growth of primary tumors and liver metastases was monitored using bioluminescent imaging.The role of PLD1 in tumor progression was assessed using western blotting,transwell migration and scratch assays,and PLD1 enzyme-mutation cell lines.Downstream PLD1 target genes were identified using quantitative real-time PCR(qPCR),transcriptome sequencing,and response blocking.The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.Results:PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis,PLD1 expression was associated with diminished survival in PDAC patients;PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver(P<0.01);Treating the SW1990 cell line with PA and choline(PLD1 pathway products)did not restore loss of PDAC cell migration and invasion ability.Transwell and scratch assays in KRM,a PLD1 catalytic-mutation cell line,suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1.qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1.A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1.A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.Conclusion:PLD1 upregulates FSTL1 expression,promotes epithelial-mesenchymal transition of tumor cells,and enhances PDAC metastasis.Thus,PLD1 blockade could inhibit PDAC progression.

Objective:To investigate mechanisms whereby phospholipase D1(PLD1)promotes pancreatic ductal adenocarcinoma(PDAC)progression.Methods:Targets were identified by screening the Genomic Spatial Event(GSE)database for genes differentially expressed in metastatic and primary tumors.Xenograft models were constructed by orthotopic injection of KPC cells into the mouse pancreas.Differential PLD1 expression in paired primary tumors and liver metastases derived from C57 mice and PDAC patients was confirmed using immunohistochemical staining.The effect of PLD1 expression on PDAC prognosis was assessed using a PDAC tissue microarray and clinical data.The effect of PLD1 expression on PDAC metastasis was assessed using transwell migration and scratch assays of cell lines ectopically expressing/silencing PLD1.The role of PLD1 in tumor metastasis was investigated using xenograft models constructed by orthotopic injection of PLD1-overexpression cell lines or vector control into the pancreas of C57 mice.Growth of primary tumors and liver metastases was monitored using bioluminescent imaging.The role of PLD1 in tumor progression was assessed using western blotting,transwell migration and scratch assays,and PLD1 enzyme-mutation cell lines.Downstream PLD1 target genes were identified using quantitative real-time PCR(qPCR),transcriptome sequencing,and response blocking.The effect of downstream target FSTL1 on liver metastasis in mice was assessed using bioluminescent imaging.Results:PLD1 expression was significantly higher in metastases than in primary tumors in KPC mice and patients.In the tissue microarray analysis,PLD1 expression was associated with diminished survival in PDAC patients;PLD1 overexpression in MIA PaCa-2 cells or knockdown in SW1990 cells could significantly affect the ability of invasion and migration.Xenograft models were established via orthotopic injections of the KPC cell line into the pancreas.Bioluminescent imaging demonstrated that PLD1 overexpression significantly increased signal intensity in the mouse liver(P<0.01);Treating the SW1990 cell line with PA and choline(PLD1 pathway products)did not restore loss of PDAC cell migration and invasion ability.Transwell and scratch assays in KRM,a PLD1 catalytic-mutation cell line,suggested that PLD1 activity is not required for PDAC metastasis;Transcriptome sequencing identified FSTL1 as a downstream molecule of PLD1.qPCR confirmed the consistency of mRNA levels between PLD1 and FSTL1.A blocking-rescue experiment suggested that FSTL1 is a downstream target of PLD1.A splenectomy metastasis model was constructed by injecting nude mice with tumor cells overexpressing FSTL1 and the results confirmed that overexpression of FSTL1 could induce liver metastases in PDAC cell due to tumor progression.Conclusion:PLD1 upregulates FSTL1 expression,promotes epithelial-mesenchymal transition of tumor cells,and enhances PDAC metastasis.Thus,PLD1 blockade could inhibit PDAC progression.

Objective To explore the effects of case method teaching in the medical postgraduate student of dermatology English teaching. Methods The experiment group was taught by case method teaching, and the control group was taught by traditional teaching model. The quantitative research and questionnaire investigation were used to evaluate the teaching methods. Results (1) There were significant differences in professional English test scores of Dermatology between the two groups;(2) The questionnaire investigation revealed that the case method teaching have achieved a higher evaluation from students in stimulating their enthusiasm of learning English,cultivating their ability of using language and improving capability of resolving clinical problem. Conclusion Case method teaching could help students cultivate the abilities to interpersonal communication and cooperation, raise the sense of innovation and innovation capacity,strengthen the relation between skills and theoretical knowledge, and improve the ability of self-management, learn cooperation and information literacy. But we should improve the case-based teaching and evaluation methods,in order to improve the teaching method of case teaching quality.

Objective To estimate the significance of E-selectin and P-selectin in nodular vasculitis.Methods The EnVision two-step method was used to measure the expression of E-selectin and P-selectin in skin samples from the lesions of 70 patients with nodular vasculitis and normal skin of 24 human controls. The differences between the patients and controls in the expression of E-selectin and P-selectin and relationship between their expression levels in nodular vasculitis lesions were assessed. Results The expression of E-selectin was detected in all the specimens of nodular vasculitis, and most of the expression level was moderately intensive (++); while E-selectin was absent in all of the control specimens. All the specimens of nodular vasculitis stained postivive for P-selectin, which was strongly (+++) expressed in most of the specimens; while only 2 control specimens stained weakly positive for P-selectin. A significant difference was observed in the expression of E-selectin and P-selectin between the specimens from the patients and controls (both P< 0.01), but not among specimens from patients at different ages and between specimens from female and male patients (all P > 0.05). In addition, the expression of E-selectin and P-selectin was well correlated with each other in lesions of nodular vasculitis (P < 0.01). Conclusions The expression of E-selectin and P-selectin is correlated with each other in lesions of acute nodular vasculitis, and is associated with the development of nodular vasculitis.

Objective To analyze the clinical and laboratory characteristics of systemic lupus erythematosus (SLE) in children. Methods Fifty-three inpatients, 5 boys and 48 girls with SLE, who aged from 7 to 14 years with a median age at 12 years, were enrolled into this study. A retrospective study was carried out to assess the clinical and laboratory features of these pediatric patients. Results The ratio of male to female patients was 1:9.6. Skin eruption was the most common initial manifestation (41.51%), followed by fever (20.75%) and arthralgia (20.75%). Systemic involvement was common, and 84.90% of these patients had hematological abnormalities, 60.38% renal involvement, 18.87% nervous involvement. The most common manifestation of hematological, renal and nervous involvement was anemia, proteinuria and seizures, respectively. Among the immunologic parameters tested, anti-nuclear antibody showed the highest positivity rate of 90.57%, followed by anti-dsDNA with a positivity rate of 67.92%. There was no significant difference between the male and female patients in the age of onset, SLEDAI score at admission and discharge, duration of hospitalization or the dose of corticosteroid used initially and at the discharge. Conclusion The manifestations of pediatric SLE are various, and multisystem involvement is common in these patients. Early diagnosis and active treatment might benefit the prognosis of pediatric SLE.