硫唑嘌呤在胰腺癌动物模型制作中的应用

目的筛选建立胰腺癌动物模型最适合成瘤的硫唑嘌呤(AZA)浓度。方法将40只SD大鼠按照AZA浓度的不同分为5组:空白对照组(A组)、2.6mg/kg AZA组(B组)、2.2mg/kg AZA组(C组)、1.8mg/kg AZA组(D组)、1.4mg/kgAZA组(E组),每组8只。A组每天灌服2mL生理盐水,B、C、D、E组每天灌服相应浓度的AZA生理盐水液2mL。第30天后进行SD大鼠皮下移植Mia PACAⅡ胰腺癌细胞悬液,通过检测大鼠血浆CA24-2和制作胰腺组织病理切片的方法来判断其是否成瘤。结果接种胰腺癌细胞后的第15、20、25、30天,各造模组大鼠血中的CA24-2水平均有不同程度的升高,其中B组在移植后的第15、20、25、30天,体内CA24-2水平分别为(51.56±2.14)、(51.61±1.21)、(54.66±1.02)、(56.00±0.38)U/mL,与C、D、E组比较,差异有统计学意义(P<0.05),且成瘤率最高,为83.3%。此外,胰腺病理切片镜下显示细胞核畸形、细胞大小不等,可见双核细胞及1～2个核仁,细胞核大且深染等病理特征,同时发现在移植部位的淋巴结和胰腺周围的淋巴结肿大。结论当AZA浓度为2.6mg/kg时,最有利于制作大鼠胰腺癌模型。     

p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

The present study was designed to investigate the effects of p-cymene on lipopolysaccharide (LPS)-induced inflammatory cytokine production both in vitro and in vivo. The production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-10 (IL-10) in LPS-stimulated RAW 264.7 cells and C57BL/6 mice was evaluated by sandwich ELISA. Meanwhile, the mRNA levels of cytokine genes were examined in vitro by semiquantitative RT-PCR. In a further study, we analyzed the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by western blotting. We found that p-cymene significantly regulated TNF-α, IL-1β, and IL-6 production in LPS-stimulated RAW 264.7 cells. Furthermore, the levels of relative mRNAs were also found to be downregulated. In in vivo trail, p-cymene markedly suppressed the production of TNF-α and IL-1β and increased IL-10 secretion. We also found that p-cymene inhibited LPS-induced activation of extracellular signal receptor-activated kinase 1/2, p38, c-Jun N-terminal kinase, and IκBα. These results suggest that p-cymene may have a potential anti-inflammatory action on cytokine production by blocking NF-κB and MAPK signaling pathways.     

Microbial transformation of asiatic acid by Alternaria longipes

Asiatic acid is a major pentacyclic triterpene isolated from Centella asiatica. It shows a variety of bioactivities. In order to obtain its derivatives, potentially useful for detailed pharmacological studies, the substrate was subjected to incubations with selected micro-organisms. In this work, asiatic acid was converted into three new compounds: 2α,3β,23,30-tetrahydroxyurs-12-ene-28-oic acid (1), 2α,3β,22β,23-tetrahydroxyurs-12-ene-28-oic acid (2), and 2α,3β,22β,23,30-pentahydroxyurs-12-ene-28-oic acid (3) by the fungus Alternaria longipes AS 3.2875. The structures of the three metabolites were determined by 1D and 2D NMR spectral data.     

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1^highYWHAZ^high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death     

ACLTOP全自动血凝仪纤维蛋白原两种测定方法的应用比较

目的：比较ACL TOP全自动血凝分析仪上Von Clauss法与PT衍生法（PT-der法）测定纤维蛋白原（FIB）的精密性及其临床应用价值。方法：用Von Clauss法与PT衍生法分别对新鲜混合血浆400例临床样本进行检测。结果：两种方法测定FIB的重复性良好;对临床样本按PT-der法检测结果分阶段做分析,FIB在1.50 g/L~3.50 g/L时,两种方法测定结果相近,差异无统计学意义（P〉0.05）,FIB〈1.50 g/L或FIB〉3.50 g/L时,PT-der法结果偏高,差异有统计学意义（P〈0.05）。结论在ACL TOP全自动血凝分析仪上,当PT-der法测出的FIB值在1.50 g/L~3.50 g/L时,直接报告结果,当PT-der法测出的FIB〈1.50 g/L或FIB值〉3.50 g/L时,以Von Clauss法复查的结果发出报告,两者结合应用可确保工作质量,提高实际工作效益。     

融入“思政元素”的情景教学法在住院医师规范化培训中的应用

目的探讨融入“思政元素”的情景教学法对在肝病科住院医师规范化培训（简称规培）中的应用效果。方法选取进行住院医师规范化培训的学生48人，随机分为两组，试验组采用融入“思政元素”的情景教学法，对照组采用传统教学法，对两组规范化培训学生理论考试、实践技能考核成绩及教学评价满意度进行比较。结果两组学生理论考试成绩无明显差异(P＞0.05）；两组学生临床实践技能得分比较，试验组在接诊患者、临床思维路径分析、医嘱处置、病案书写、医患沟通能力和实践技能总成绩得分均优于对照组(P<0.05)；两组学生教学效果调查问卷比较，试验组在提升学习兴趣、提升自主学习能力、团结协作能力、职业道德素养和总体教学满意度方面得分均明显高于对照组(P<0.05)。结论融入“思政元素”的情景教学法在肝病科住院医师规范化培训中应用，具有良好的效果。