Zearalenone Exposure Disrupts Blood–Testis Barrier Integrity through Excessive Ca2+-Mediated Autophagy

Zearalenone (ZEA), a common mycotoxin in grains and animal feeds, has been associated with male reproductive disorders. However, the potential toxicity mechanism of ZEA is not fully understood. In this study, in vivo and in vitro models were used to explore the effects of ZEA on the blood–testis barrier (BTB) and related molecular mechanisms. First, male BALB/C mice were administered ZEA orally (40 mg/kg·bw) for 5–7 d. Sperm motility, testicular morphology, and expressions of BTB junction proteins and autophagy-related proteins were evaluated. In addition, TM4 cells (mouse Sertoli cells line) were used to delineate the molecular mechanisms that mediate the effects of ZEA on BTB. Our results demonstrated that ZEA exposure induced severe testicular damage in histomorphology and an ultrastructural, time-dependent decrease in the expression of blood–testis barrier junction-related proteins, accompanied by an increase in the expression of autophagy-related proteins. Additionally, similar to the in vitro results, the dose-dependent treatment of ZEA increased the level of cytoplasmic Ca²⁺ and the levels of the autophagy markers LC3-II and p62, in conjunction with a decrease in the BTB junction proteins occludin, claudin-11, and Cx43, with the dislocation of the gap junction protein Cx43. Meanwhile, inhibition of autophagy by CQ and 3-MA or inhibition of cytoplasmic Ca²⁺ by BAPTA-AM was sufficient to reduce the effects of ZEA on the TM4 cell BTB. To summarize, this study emphasizes the role of Ca²⁺-mediated autophagy in ZEA-induced BTB destruction, which deepens our understanding of the molecular mechanism of ZEA-induced male reproductive disorders.     

整合医学模式下多模式教学在麻醉实习中的应用效果

目的 研讨整合医学模式下多模式教学在麻醉实习中的应用价值.方法 选取2017年9月至2019年9月(2013、2014级)沈阳医学院6个麻醉本科班共170名医学生作为研究对象,采用随机数表法分别设置研究组(85名)与对照组(85名).对照组采用传统教学方法,研究组采用多模式教学法,对比两组实习期结束时麻醉技术考核成绩,...     

重度牙周炎致牙齿松动脱落患者前牙美学区综合治疗1例报告及文献复习

目的：探讨重度牙周炎致前牙松动脱落患者的治疗和美学修复,阐明多学科综合治疗对前牙美学区的治疗效果,为其临床应用提供参考。方法：患者,男性,57岁,因上下前牙松动不适半年余就诊。专科检查见11、21、22、41松动Ⅲ°,42松动Ⅱ°。经多学科会诊后,行牙周基础治疗,炎症控制后,拔除11、21、22、41、42并行即刻种植,富血小板纤维蛋白（PRF）联合引导骨再生（GBR）技术修复种植体周围骨缺损。因患者美学要求,12、13、23、31、32、33、43根管治疗后行牙体预备,13-23、33-43行固定修复。结果：种植术后显示种植体位置良好,种植体周围骨量充足,口内见牙龈软组织愈合良好,牙槽嵴丰满度较好;修复完成后较好地恢复了患牙的咀嚼发音功能,患者对美学效果满意。结论：通过多学科综合治疗的应用,成功实现了对重度牙周炎患者前牙美学区的种植修复,为前牙美学区的诊疗开辟了新途径。     

不同粘结条件下健康成人牙本质中MMP-2和MMP-9表达水平及其意义

目的：探讨不同粘结条件下健康成人牙本质中基质金属蛋白酶2（MMP-2）和基质金属蛋白酶9（MMP-9）表达水平,为临床应用基质金属蛋白酶（MMPs）抑制剂提高粘结效果提供依据。方法：收集20颗成人新鲜离体磨牙,液氮冷却条件下将其研磨为牙本质粉;模拟口内条件,对牙本质分别进行自酸蚀粘结（Single Bond Universal）和全酸蚀粘结（35%磷酸凝胶+Adpter Single Bond 2）处理,以不进行任何处理的牙本质作为阴性对照组,10%磷酸溶液（自酸蚀粘结）或10%磷酸溶液+35%磷酸凝胶处理的脱矿牙本质粉（全酸蚀粘结）处理的牙本质作为阳性对照组,只进行Single Bond Universal （自酸蚀粘结）处理和35%磷酸凝胶+Adpter Single Bone2（全酸蚀粘结）处理的牙本质作为空白对照组;在粘结过程中分别使用MMPs抑制剂氯己定（CHX）和米诺环素（MI）预处理,作为CHX预处理组和MI预处理组;采用10%次氯酸钠进行牙本质老化,作为老化组,并在老化组基础上加入CHX和MI作为CHX预处理老化组和MI预处理老化组。采用明胶酶谱法进行聚丙烯酰胺凝胶电泳,孵育染色脱色后,采用凝胶图像分析系统分析条带,计算各组牙本质中MMP-2和MMP-9表达水平。结果：在自酸蚀粘结条件下,与空白对照组比较,CHX预处理组牙本质中MMP-2和MMP-9表达水平降低（P<0.05）,MI预处理组牙本质中MMP-2和MMP-9表达水平降低（P<0.05）;与空白老化对照组比较,CHX预处理老化组牙本质中MMP-2和MMP-9表达水平降低（P<0.05）,MI预处理老化组牙本质中MMP-2和MMP-9表达水平降低（P<0.05）。在全酸蚀粘结条件下,与空白对照组比较,CHX预处理组和MI预处理组牙本质中MMP-2表达水平降低（P<0.05）;与空白老化对照组比较,CHX预处理老化组与MI预处理老化组牙本质中MMP-2表达水平降低（P<0.05）。结论：在牙本质粘结过程中,CHX和MI能够通过降低MMP-2和MMP-9表达水平减缓酶解反应,从而增强粘结强度。     

伊班膦酸钠对肝癌并骨转移骨钙素及骨碱性磷酸酶的影响

目的：探讨骨钙素（osteocalcin,OST）、骨碱性磷酸酶（bone alkaline phosphatase,BAP）对肝癌并骨转移的预测作用及其伊班膦酸钠对骨代谢的影响。方法收集肝癌并骨转移患者16例、肝癌并非骨转移患者22例及肝癌无转移患者20例,并予伊班磷酸钠治疗肝癌并骨转移组,检测各组及肝癌并骨转移治疗前、治疗28、56及84 d骨钙素、骨碱性磷酸酶水平,比较各组间及治疗前后其差异。结果肝癌并骨转移组、肝癌非骨转移组、无转移组血清骨钙素水平分别为31.12±4.18、13.00±6.92、10.23±1.34,骨碱性磷酸酶分别为20.11±1.65、11.41±1.25、10.78±1.35,其中骨转移组骨钙素及骨碱性磷酸酶水平较其他两组差异有统计学意义（P ＜0.05）。伊班膦酸钠注射液可降低肝癌骨转移组骨钙素及骨碱性磷酸酶水平,治疗后较治疗前差异有统计学意义（ P ＜0.05）。结论骨钙素、骨碱性磷酸酶对肝癌并骨转移患者有较好的预测作用,伊班膦酸钠注射液可有效治疗骨转移瘤,机制可能与降低骨钙素及骨碱性磷酸酶相关。     

Inhibition of arsenic-induced rat liver injury by grape seed exact through suppression of NADPH oxidase and TGF-β/Smad activation

Chronic arsenic exposure induces oxidative damage to liver leading to liver fibrosis. We aimed to define the effect of grape seed extract (GSE), an antioxidant dietary supplement, on arsenic-induced liver injury. First, Male Sprague-Dawley rats were exposed to a low level of arsenic in drinking water (30 ppm) with or without GSE (100 mg/kg, every other day by oral gavage) for 12 months and the effect of GSE on arsenic-induced hepatotoxicity was examined. The results from this study revealed that GSE co-treatment significantly attenuated arsenic-induced low antioxidant defense, oxidative damage, proinflammatory cytokines and fibrogenic genes. Moreover, GSE reduced arsenic-stimulated Smad2/3 phosphorylation and protein levels of NADPH oxidase subunits (Nox2, Nox4 and p47phox). Next, we explored the molecular mechanisms underlying GSE inhibition of arsenic toxicity using cultured rat hepatic stellate cells (HSCs). From the in vitro study, we found that GSE dose-dependently reduced arsenic-stimulated ROS production and NADPH oxidase activities. Both NADPH oxidases flavoprotein inhibitor DPI and Nox4 siRNA blocked arsenic-induced ROS production, whereas Nox4 overexpression suppressed the inhibitory effects of GSE on arsenic-induced ROS production and NADPH oxidase activities, as well as expression of TGF-β1, type I procollagen (Coll-I) and α-smooth muscle actin (α-SMA) mRNA. We also observed that GSE dose-dependently inhibited TGF-β1-induced transactivation of the TGF-β-induced smad response element p3TP-Lux, and that forced expression of Smad3 attenuated the inhibitory effects of GSE on TGF-β1-induced mRNA expression of Coll-I and α-SMA. Collectively, GSE could be a potential dietary therapeutic agent for arsenic-induced liver injury through suppression of NADPH oxidase and TGF-β/Smad activation.     

共识会议法在中医临床实践指南中的应用现状分析

目的:探讨共识会议法在中医临床实践指南中的应用现状及存在问题。方法:采用计算机检索和手工检索相结合的方法,检索1978年1月~2010年8月发表的采用共识会议法制定的中医临床实践指南。对指南的制定组织、发表时间、专家遴选的范围、专家来源的机构、专家的职称、专家的工龄、专家的数量、会议的轮次数、共识会议法用于解决的问题进行分析。结果:共纳入155个指南,其中134个指南是由医院组织制定的;151个指南是在1996年~2010年发表的。105个指南的编写组专家来源于省市级;148个指南的编写组专家来源于医院;124个指南的编写组专家由初级职称以上人员组成;149个指南的编写组专家平均工龄在10年以上。专家的平均数量为11.14±2.75;会议的平均轮次为3.72±0.69;共识会议法被用于形成127个指南的全部内容。结论:共识会议法是中医临床实践指南制定的主要方法,而专家的来源范围、专家的构成及其专家的数量有待于进一步规范。     

中医药现代化、国际化的策略是标准化

由于中医药诊疗模式适应现代疾病谱,并具有"整体观、恒动观、时空观"等特色,其在国内外发展迅速。然而,受中医思维逐步淡化、中药质量存疑、疗效评价方法不当及虚假医疗屡禁不止等诸多因素干扰,中医药临床疗效遭到质疑,加上安全事故频发,导致中医药公信力急剧下降。同时中医药国际化道路曲折,深陷技术贸易壁垒及"去中国化"等一系列困境。中医药标准化作为中医药特色和优势的重要载体,是实现中医药现代化和国际化的前提。本文认为中医药在发展过程中要想摆脱上述困扰,必须走标准化的道路,并提出了借助标准化维护公信力、传承中医诊疗技术和保障中药质量和安全、克服技术贸易壁垒及纠正"去中国化"等系列策略和建议。