Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.     

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

脑卒中患者急性应激障碍及影响因素研究

目的探讨脑卒中患者急性应激障碍发生现状及影响因素。方法采用斯坦福急性应激反应问卷对349例脑卒中住院患者进行调查。结果共163例(46.70%)患者发生急性应激障碍;Logistic回归分析结果显示,患者性格、是否存在偏瘫及是否吞咽功能障碍是脑卒中患者发生急性应激障碍的主要影响因素(P0.05,P0.01)。结论脑卒中患者急性应激障碍发生率较高,内向性格及存在偏瘫和吞咽功能障碍的患者更容易发生急性应激障碍。医护人员应及时为高危患者提供个体化治疗及预见性护理,防止脑卒中患者发生急性应激障碍。     

骨形态发生蛋白2及碱性成纤维生长因子2对大鼠骨髓间充质干细胞膜片增殖和成骨分化的影响

文题释义： 细胞膜片技术：是在体外接种培养高密度的细胞，使其相互融合生长至100%而形成的透明致密膜状物。该技术不需要胰酶消化即可收集细胞，因此保留了大量的胞外基质、细胞间连接以及细胞-基质连接等结构。目前细胞膜片技术已成为组织工程领域的研究热点，已被推广应用于牙周膜、角膜、心脏、软骨、食管等多种组织器官修复。 成骨细胞：主要由内外骨膜和间充质始祖细胞分化而来，在复杂的骨形成过程中发挥着主要的功能，承担着骨基质的合成、分泌和矿化。骨髓间充质干细胞具有多向分化潜能，能定向分化为成骨细胞，其成骨分化过程可受多种因素的影响，如细胞因子的调控、遗传因素和激素水平等。背景：现阶段骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖、成骨分化的影响和作用机制还尚未可知，如何将生长因子与组织工程细胞膜片技术相整合，最终将其用于骨缺损修复具有重要意义。 目的：探讨单独及联合应用骨形态发生蛋白2和碱性成纤维生长因子2对骨髓间充质干细胞膜片增殖和成骨分化的影响。 方法：体外分离培养鉴定SD大鼠骨髓间充质干细胞并构建细胞膜片，选用不同质量浓度的骨形态发生蛋白2和碱性成纤维生长因子2单独及联合诱导骨髓间充质干细胞膜片，CCK-8法结合碱性磷酸酶活性检测确定2种因子促进膜片增殖和成骨分化的最佳有效质量浓度；然后对骨髓间充质干细胞膜片进行成骨诱导，通过大体及显微镜观察、Vonkossa染色、茜素红染色、RT-PCR检测相关成骨标志物来评估诱导效果。 结果与结论：单独应用骨形态发生蛋白2可增强骨髓间充质干细胞膜片的碱性磷酸酶活性，最佳质量浓度为100 μg/L(P < 0.001)，单独应用碱性成纤维生长因子2能加速骨髓间充质干细胞膜片的增殖，最佳质量浓度为20 μg/L(P < 0.001)，而联合应用既可以促进膜片增殖又能提高其碱性磷酸酶活性(P < 0.001)；经成骨诱导后，4组膜片在形态学上无明显差异，均能诱导骨髓间充质干细胞膜片的成骨分化，其中联合组钙结节最明显(P < 0.001)，可显著促进膜片晚期成骨分化并抑制其早期成骨分化，具有明显的协同促进作用(P < 0.001)。结果表明，骨形态发生蛋白2和碱性成纤维生长因子2联合应用时具有协同作用，既可以促进骨髓间充质干细胞膜片增殖，又能显著增强其成骨诱导能力。ORCID: 0000-0003-1918-579X(何惠宇) 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程     

2013-2017年我国四种恶性肿瘤住院费用水平及结构变动度分析

背景　恶性肿瘤给家庭、社会带来了沉重的医疗、经济负担，极易导致部分家庭“因病致贫”或放弃治疗，目前相关研究多集中于单一病种、分散地域的研究，仍缺乏对于全国范围与多病种恶性肿瘤住院费用变化及结构构成的考量。目的　分析2013-2017年我国4种恶性肿瘤住院费用水平以及影响住院费用的主要项目和结构变动情况，为控制医疗费用上涨、深化新医改提供参考依据。方法　本研究数据来源于《2014中国卫生和计划生育统计年鉴》《2015中国卫生和计划生育统计年鉴》《2016中国卫生和计划生育统计年鉴》《2017中国卫生和计划生育统计年鉴》以及《2018中国卫生健康统计年鉴》，样本跨度为2013-2017年。统计“30种疾病人均住院费用”中的胃恶性肿瘤、肺恶性肿瘤、食管恶性肿瘤以及膀胱恶性肿瘤的数据，4种恶性肿瘤的人均住院费用包括药费、检查费、治疗费、手术费和手术材料费。2019年4-8月，采用结构变动度法分析我国2013-2017年4种恶性肿瘤的住院费用的结构变动情况〔结构变动值（VSV）、结构变动度（DSV）、结构变动贡献率〕。结果　2013-2017年，4种恶性肿瘤的人均住院费用逐年上升，其中胃恶性肿瘤的人均住院费用始终最高，且肺恶性肿瘤的人均住院费用上升幅度最大。2013-2017年，在4种恶性肿瘤住院各项费用的占比中，药费占比最高且总体逐年下降。从4种恶性肿瘤住院各项费用的实际变化来看，药费在2013-2014年有所上升，2014-2017年逐年下降；检查费在2013-2014年下降，2014-2017年缓慢上升；手术费与手术材料费在2013-2017年逐年上升。2013-2017年，在4种恶性肿瘤住院各项费用中均是药费的VSV最大；4种恶性肿瘤药费、检查费的VSV均呈负向变化，手术费和手术材料费的VSV均呈正向变化，治疗费的VSV增减均不明显。2013-2017年，4种恶性肿瘤住院费用的DSV从大到小依次为肺恶性肿瘤、胃恶性肿瘤、食管恶性肿瘤、膀胱恶性肿瘤。2013-2017年，4种恶性肿瘤住院各项费用中均是药费的结构变动贡献率最大，治疗费的结构变动贡献率最小；除药费外，胃恶性肿瘤、肺恶性肿瘤住院各项费用中均是手术材料费和手术费的结构变动贡献率次之，食管恶性肿瘤住院各项费用中手术费、检查费的结构变动贡献率次之，膀胱恶性肿瘤住院各项费用中检查费、手术材料费的结构变动贡献率次之。结论　2013-2017年我国4种恶性肿瘤手术费的结构变动贡献率虽然较为理想，但药费、治疗费仍是住院费用结构的重点调整对象；同时为有效降低恶性肿瘤的人均住院费用，应当加强控制手术材料费与检查费；而胃恶性肿瘤与肺恶性肿瘤患者的疾病经济负担严重，若要缓解应加强疾病的早期预防与住院费用管控。     

基于雨课堂的临床流行病学教学改革与实践

目的探讨雨课堂在临床流行病学教学中的作用和效果。方法采用随机对照法在本科阶段无流行病学学习经历的临床专业硕士研究生中,使用雨课堂线上课前预习及课后随堂练习的功能,用于评价雨课堂线上功能的辅助教学效果。结果应用雨课堂线上功能干预组与对照组在基线、阶段小测和末考卷面成绩均无统计学差异;但对于主动学习,雨课堂参与度较高的学生成绩提高明显。结论雨课堂有利于理论性较强课程的学习,但是仍不能忽略课堂教学师生互动过程。     

Investigation of Bimetallic Nickel Catalysts in Catalyst‐Transfer Polymerization of π‐Conjugated Polymers

A comparative study involving bimetallic nickel catalysts designed from disubstituted N,N,N′,N′‐tetra(diphenylphosphanylmethyl)benzene diamine bridging ligands is reported. Catalyst behavior is explored in the Kumada catalyst‐transfer polymerization (KCTP) using poly(3‐hexylthiophene) (P3HT) as the model system. The success of a controlled polymerization is monitored by analyzing monomer conversion, degree of polymerization, end‐group identity, and molecular weight distribution. The characterization of P3HT obtained from KCTP initiated with the bimetallic catalysts shows chain‐growth behavior; however, the presence of Br/Br end‐groups and broader molecular weight distribution reveals a reduced controlled polymerization compared to the commonly employed Ni(dppp)Cl₂. The observed increase in intermolecular chain transfer and termination processes in KCTP initiation with the bimetallic catalysts can be attributed to a weaker Ni(0)‐π‐aryl complex interaction, which is caused by increased steric crowding of the coordination sphere.