Higher medical education should bring the superiority of the course into play,and develop the bioethics education effectively.We should arouse medical undergraduate's respect and enthusiasm for bioethics,help them reevaluate their value concept and learn to use basic theory of bioethics to guide the medical service.Thus medical science can develop in a healthy way.

ObjectiveTo evaluate the sufficiency of dialysis and nutri ti onal status of 44 end-stage renal disease (ESRD) with urea metabolic parameters such as TACurea,KT/V and PCR.MethodClinical data were collecte d and analyzed with statistic methods.ResultsTACurea and PCR w ere significantly lower in patients in insufficient dialysis group than those in sufficient dialysis group.There was no statistical difference between the two g roups in terms of KT/V.PCR was not influenced by KT/V in sufficient dialysis gro up,while it was significantly influenced by KT/V in insufficient dialysis group. ConclusionTACurea and PCR are significant indicators to assess whether the blood dialysis is sufficient or not in the long run.KT/V can direct ly indicate the effectiveness of single dialysis.Therefore,it is the best indica tor for adjusting the dialytic strategy.However,it is not important if the dialy sis is not sufficient.

Glomus Tumor ; diagnosis ; Humans ; Lung ; pathology

Objective: To investigate the clinicopathological features, morphological characteristics, immunophenotypes of littoral cell angioma (LCA) in spleen, and to provide new evidence for making diagnosis and avoiding misdiagnosis.Methods: Clinicopathological data, histological characteristics of 13 cases of LCA were retrospectively studied and immunohistochemical staining was imposed on the paraffi-nembedded specimens, and 5 cases of cavernous hemangioma, 4 cases of normal littoral cells of spleens were used as control groups, simultaneously.Results: All the 13 LCA patients included 7 males and 6 females, aged from 39 to 70 years with an average of 54.2 years and a median age of 55 years.Among these tumor patients, 6 cases were accompanied by malignances, benign tumors or inflammation states at abdominal cavities, and 7 cases were accidentally discovered by physical examinations.Grossly, spleens contained solitary or multiple gray red nodules ,which ranged from 0.5 to 6.2 cm in diameter.Histologically, tumors were composed by anastomosing vascular spaces which were lining by plump, rounded to cuboidal littoral cells that extended into vascular lumens.Usually, papillary frameworks that were covered by these cells were also seen extending into the lumens in some areas.Other types of histiocytoid cells were identified in lumens and the sizes were larger than the littoral cells.Both types of cells absented cytologic atypia.Immunohistochemical study demonstrated that the littoral cells in all cases were positive for vascular endothelial and histiocyte markers, such as CD21, CD31, CD68, polyclone FⅧRAg and ERG, while these cells were negative for CD8, CD34, and WT-1.These findings manifested that immunophenotype of littoral cell in LCA distinctive from that in controls.Conclusion: LCA is a benign lesion, which frequently occurs in the elderly.Its etiology remains confusion, however, immune dysregulation may associate with it because of the concomitance with other tumor or inflammation in some cases.The littoral cells in LCA show a hybrid endothelial-histiocytic phenotype on immunohistochemistry, therefore these cells may have features that intermediate between those of endotheliocytes and histiocytes.Emphasizing the histological findings and immunophenotypes is significant for diagnosis and differential diagnosis.

Objective:To investigate the effects and underlying mechanisms of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/NF-κB signaling pathway in human kidney-2(HK-2) cells of hyperuricemic nephropathy.Methods:HK-2 cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was induced by high uric acid (720 μmol/L) immersion for 48 h to establish a cell model of hyperuricemic nephropathy in vitro and subsequently divided into hyperuricemic group, overexpressed protease activated receptor 2 (PAR2) and knockdown PAR2 group. The expressions of PAR2, PI3K, AKT, NF-κB mRNA were measured by real-time PCR. The expressions of PAR2, PI3K, AKT and NF-κB protein were measured by Western blotting. The expressions of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), pro-interleukin-1β (pro-IL-1β), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) were detected by enzyme linked immunosorbent assay (ELISA). Results:(1) Compared with the control group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in hyperuricemic group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant in hyperuricemic group were significantly increased (all P<0.01). (2) Compared with the hyperuricemic group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in overexpressed PAR2 group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, IL-1β and TGF-β1 in the supernatant were significantly increased (all P<0.05). (3) Compared with the hyperuricemic group, the expression of PAR2, PI3K, AKT and NF-κB mRNA and protein in knockdown PAR2 group were significantly decreased (all P<0.05), the expressions of IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant were significantly decreased (all P<0.05). Conclusions:In the process of uric acid-induced HK-2 cell damage, uric acid significantly up-regulates the expression of PI3K/AKT/NF-κB signaling pathway by activating PAR2, leading to a marked increase in inflammatory damage. Knocking down PAR2 inhibits the expression of PI3K/AKT/NF-κB signaling pathway, which can effectively reduce the inflammatory damage of HK-2 cells.

Objective:To establish a mouse model of intra-jugular arteriovenous fistula (AVF) to screen differentially expressed genes in the process of intimal stenosis of AVF for investigating the abnormal expression signaling pathways and the mechanisms.Methods:Forty-six male C57BL/6 mice were randomly divided into AVF group ( n=23) and sham-operated group ( n=23). The AVF group underwent internal jugular arteriovenous fistuloplasty, and the sham-operated group separated the right external jugular vein and common carotid artery and then sutured the incision. The whole-genome sequences of mice with AVF stenosis were determined by transcriptomic reversible chain terminator and synthetic sequencing. The microarray data set was established, and the Benjamini & Hochberg method of gene microarray data analysis was applied to screen the differentially expressed genes. The differentially expressed genes were screened by R-language enrichment analysis. Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were performed. The subcellular localization of the differentially expressed genes was performed by BUSCA software. The protein network interaction of differentially expressed genes was analyzed by using STRING database and Cytoscape software. Results:In the AVF group, 21 mice were successfully modeled and 2 mice failed. Therefore, there were 21 mice in the AVF group and only 21 mice in the sham-operated group. This mouse internal jugular AVF model was innovated using the continuous-interrupted suture method, which improved the success rate of modeling this model. The differential gene sequencing analysis showed that there were 2 514 differentially expressed genes in the AVF process, including 1 323 up-regulated genes and 1 191 down-regulated genes. GO functional enrichment analysis showed that the differential genes were mainly enriched in metabolic process, activation, redox, mitochondria and so on. KEGG pathway enrichment analysis showed that the differential genes were enriched in metabolism, energy substance synthesis, diabetes, oxidative stress and so on. Statistical analysis of subcellular localization showed that the differences were mainly in mitochondrial proteins (24.24%), cytoplasmic proteins (17.51%), nuclear proteins (13.13%), cell membrane proteins (11.45%), and extracellular proteins (10.77%).Conclusions:Mitochondrial oxidative stress injury may be involved in the pathological damage process of endothelial proliferation stenosis in the AVF.

Objective To observe the level of CD4+CD25+ regulatory T cells (CD4+CD25+ Treg cells) with positive fork head transcription factor 3 (Foxp3) and changes of T-box transcription factor TBX1 (TBX1) and myocyte specific enhancer 2D (MEF2D) expression in peripheral blood of rats with acute rejection after renal transplantation,and to investigate its regulatory mechanisms by combined with renal function,plasma interleukin-10 (IL-10),interferon-γ (IFN-γ) and renal histopathological changes.Methods Rat renal transplantation model was established and divided into two groups:acute rejection group (AR group) and non-acute rejection group (non-AR group).Their renal function including serum creatinine (Scr) and blood urea nitrogen (BUN) in plasma was measured.The renal histopathology was observed by HE staining.Levels of IL-10 and IFN-γ in plasma were detected by ELISA.The proportion of CD4+CD25+ Treg cells was measured by flow cytometry.The mRNA expressions of Foxp3,TBX1 and MEF2D in CD4+CD4+Treg cells were detected by real-time PCR,and their protein expressions were tested by Western blotting.Results Compared with these in the non-AR group,the levels of BUN,Scr and IFN-γ significantly increased in AR group (all P ＜ 0.05),while IL-10 decreased (P ＜ 0.05).Renal histopathology in the acute rejection group showed glomerular hypertrophy and mesangial cell proliferation,capillary proliferation and neutrophil infiltration;renal interstitial edema and tubular necrosis,accompanied by lymphocytes,plasma cells and neutrophils infiltration.Compared with that in the non-AR group,the percentage of CD4+CD25+ Treg cells in peripheral blood was notably lowered in AR group (4.50％±0.50％ vs 5.74％±1.96％,P ＜ 0.05).The mRNA and protein expressions of Foxp3 and MEF2D were lower in AR group than those in non-AR group,while the expressions of TBX1 was elevated (all P ＜ 0.05).Conclusions In rats with acute renal allograft rejection,the percentage of CD4+CD25+ Treg cells and expressions of Foxp3,MEF2D and IL-10 decrease,while the expressions of TBX1 and IFN-γ enhance.These participate in the development of acute rejection after renal transplantation,and aggravate the renal damage.

Objective: To explore the role of PDK1 in the transition of endothelial to hematopoietic cells and its effect on the generation and normal function of HSC. Methods: PDK1 was deleted specifically in endothelial cells expressing VEC (Vascular Endothelial Cadherin). CFU-C was performed to detect the effect of PDK1 on the function of hematopoietic progenitor cells using the cells from PDK1^fl/fl, PDK1^fl/+ and Vec-Cre; PDK1^fl/fl AGM region. Hematopoietic stem cell transplantation assay was conducted to determine the effect of PDK1 on hematopoietic stem cells. Flow cytometry was performed to analyze the influence of PDK1 on percentage, cell cycle and apoptosis of CD31⁺c-Kit^high cell population. Real-time PCR was conducted to measure the expression of transcription factors involved in process of transition from endothelial to hematopoietic cells. Results: In contrast to the wild type group, the CFU from PDK1-deficient hematopoietic progenitor cells showed smaller in morphology and fewer in quantity. CFU-GM was (24±5)/ee in knockout group, and the control group was (62±1)/ee (P=0.001). PDK1 deletion severely impaired the ability to repopulate hematopoietic cells and differentiate into committed cells. hematopoietic progenitor cells from knockout group was transplanted into 5 recipients without any recipients reconstructed. However, 5 of 7 recipients were reconstructed in control group (P=0.001). The proportion of intra-vascular clusters in the AGM was decreased (the frequency of CD31⁺c-Kit^high in the knockout group was (0.145±0.017)%, and the control group ratio was (0.385±0.040)% (P=0.001), but not due to the inhibition of cell proliferation and/or increase of apoptosis. Further study found that the absence of endothelial PDK1 causes a decreased expression of RUNX1, P2-RUNX1, GATA2 and other important hematopoietic-related transcription factors in hemogenic cluster. Conclusion PDK1 deletion impairs the transition of endothelial cells to hematopoietic cells as well as the generation and function of HSC.

Objective:To explore the effect of hydroxysafflor yellow A (HSYA) on the viability of the random skin flap in rats.Methods:A total of 30 SD rats were randomly divided into HSYA group and normal saline (NS) group. Using the modified McFarlane skin flap model, a rectangular random skin flap of approximately 3 cm×12 cm was dissected and sutured in situ over the central dorsum of the rats. The flap was divided into four zones from its caudal part to the cranial part: Zone Ⅰ, Zone Ⅱ, Zone Ⅲ, and Zone Ⅳ. The rats in the HSYA group received intraperitoneal injection of HSYA (20 mg/kg) dissolved in 0.9% sodium chloride solution immediately, while NS group rats were given intraperitoneal injection of an equal amount of NS. The injection was performed once a day for 14 days. On postoperative day 14, the flap was photographed to evaluate the survival rate. Tissue samples were collected from Zone Ⅲ of the flaps for histological analysis and real-time quantitative PCR (RT-qPCR). The number of the vessels with a diameter greater than 0.1 mm in the subdermal layer was evaluated using hemotoxylin & eosin (HE) staining. Microvascular density in the subdermis was assessed by the immunohistochemical (IHC) staining of CD31. The gene expression levels of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor 2 (VEGFR2) was quantified with RT-qPCR. Results:The mean survival rate of HSYA group (70.4%±7.0%) was significantly higher than that of NS group (55.4%±7.7%, P<0.01). The number of blood vessels > 0.1 mm in the HSYA group (31.5±5.0) was significantly higher than that in the NS group (15.3±3.4, all P<0.01). The mean microvascular density in HSYA group (82.8±14.0/mm 2) was significantly greater than that in NS group (43.0±4.6/mm 2,P<0.01). Compared with NS group, the mRNA expression of eNOS and VEGFR2 was upregulated in HSYA group (3.0±0.9 vs. 1.2±0.8; 14.2±7.7 vs. 1.1±0.6; P<0.05). Conclusions:HSYA might promote the vasodilation and angiogenesis through up-regulating eNOS and VEGFR2 expression, thus increasing the viability of the random skin flap.

Objective:To explore the effect of hydroxysafflor yellow A (HSYA) on the viability of the random skin flap in rats.Methods:A total of 30 SD rats were randomly divided into HSYA group and normal saline (NS) group. Using the modified McFarlane skin flap model, a rectangular random skin flap of approximately 3 cm×12 cm was dissected and sutured in situ over the central dorsum of the rats. The flap was divided into four zones from its caudal part to the cranial part: Zone Ⅰ, Zone Ⅱ, Zone Ⅲ, and Zone Ⅳ. The rats in the HSYA group received intraperitoneal injection of HSYA (20 mg/kg) dissolved in 0.9% sodium chloride solution immediately, while NS group rats were given intraperitoneal injection of an equal amount of NS. The injection was performed once a day for 14 days. On postoperative day 14, the flap was photographed to evaluate the survival rate. Tissue samples were collected from Zone Ⅲ of the flaps for histological analysis and real-time quantitative PCR (RT-qPCR). The number of the vessels with a diameter greater than 0.1 mm in the subdermal layer was evaluated using hemotoxylin & eosin (HE) staining. Microvascular density in the subdermis was assessed by the immunohistochemical (IHC) staining of CD31. The gene expression levels of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor receptor 2 (VEGFR2) was quantified with RT-qPCR. Results:The mean survival rate of HSYA group (70.4%±7.0%) was significantly higher than that of NS group (55.4%±7.7%, P<0.01). The number of blood vessels > 0.1 mm in the HSYA group (31.5±5.0) was significantly higher than that in the NS group (15.3±3.4, all P<0.01). The mean microvascular density in HSYA group (82.8±14.0/mm 2) was significantly greater than that in NS group (43.0±4.6/mm 2,P<0.01). Compared with NS group, the mRNA expression of eNOS and VEGFR2 was upregulated in HSYA group (3.0±0.9 vs. 1.2±0.8; 14.2±7.7 vs. 1.1±0.6; P<0.05). Conclusions:HSYA might promote the vasodilation and angiogenesis through up-regulating eNOS and VEGFR2 expression, thus increasing the viability of the random skin flap.