农村订单定向医学生培养第二课堂的形式与教学

根据农村订单定向医学生免费本科医学教育人才培养模式改革试点的要求，落实卓越医生教育培养计划目标，以第二课堂为载体，以建立居民健康档案与开展居民健康管理为教学形式和教学内容，通过建立档案、病种筛选、自主学习、教师指导、健康管理、家庭访视、信息维护等方式，为农村订单定向医学生打下基层医疗卫生服务的坚实基础，并促进综合实践能力全面提升。     

肌电生物反馈对痉挛型脑瘫患儿下肢运动功能影响的Meta分析

目的:应用Meta分析评价肌电生物反馈治疗痉挛型脑瘫的作用。方法:检索PubMed、Embase、Cochrane图书馆及中国生物医学文献数据库、CNKI、维普、万方数据库中2009年1月~2019年6月关于肌电生物反馈治疗痉挛型脑瘫的随机对照试验,利用RevMan 5.3软件进行Meta分析。结果:纳入10项随机对照试验,共613个病例;肌电生物反馈可以改善脑瘫患儿踝关节活动度(MD=5.06,95%CI=4.01~6.10,P<0.01),改善粗大运动功能(GMFM D区MD=3.75,95%CI=2.75~4.75,P<0.01;GMFM E区MD=6.04,95%CI=4.82~7.26,P<0.01),改善腓肠肌痉挛程度(MD=5.19,95%CI=-0.52^-0.39,P<0.01)。结论:肌电生物反馈在改善脑瘫患儿下肢运动功能方面具有一定效果,但所纳入研究的方法有局限性,还需更严格的设计和高质量的研究方法进一步证明。     

雷公藤甲素对宫颈癌患者免疫功能及肿瘤细胞增殖的影响

目的：探讨雷公藤甲素（triptolide）对宫颈癌患者免疫功能和肿瘤细胞增殖的作用。方法：选取2015 年7 月至2018 年4 月河北北方学院附属第二医院妇产科收治的62 例宫颈癌患者，通过随机数字法分为观察组和对照组，每组各31 例。两组患者均在腹腔镜手术后接受常规治疗，观察组患者联合雷公藤甲素进行治疗。观察、比较两组患者的疗效、血清免疫细胞和炎症反应因子以及细胞周期蛋白D1（cyclinD1）、雌激素受体α（ERα）水平。结果：观察组宫颈癌患者治疗后的客观缓解率显著高于对照组（87.10% vs 61.29%，P<0.05）。治疗后两组CD3+和CD4+T淋巴细胞以及CD4+/CD8+T淋巴细胞比值均显著升高，观察组显著高于对照组；两组CD8+及PD-L1 T淋巴细胞均显著下降，观察组显著低于对照组（P<0.01）。治疗后，两组患者IL-6、IL-10 以及TNF-α 水平均显著下降，观察组显著低于对照组（P<0.01）。治疗后，两组患者cyclinD1 阳性表达率均显著下降、ERα 阳性表达率均显著升高（均P<0.05）；两组间cyclinD1 和ERα 阳性表达率比较差异无统计学意义（均P>0.05）。结论：在常规手术治疗的基础上，雷公藤甲素可有效改善宫颈癌术后患者的免疫功能、降低机体炎症反应、抑制肿瘤细胞的增殖，对宫颈癌具有一定的治疗效果。     

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

Combining proteomics and lipid analysis to unravel Confidor stress response in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae is a useful model for studying the influence of different stress factors on eukaryotic cells. In this work we used the pesticide imidacloprid, in the Confidor formulation, as the stress factor and analyzed its influence on the metabolic activity, proteome and lipid content and composition of Saccharomyces cerevisiae yeast. During the cultivation of yeast, the lowest recommended application dose of Confidor (0.025%, v/v) was added to the growth media and its influence on the mitochondria, cytosol with microsomes, and the whole yeast cells was monitored. The results show that under the stress provoked by the toxic effects of Confidor, yeast cells density significantly decreased and the percentage of metabolically disturbed cells significantly increased comparing with untreated control. Also, there was a downregulation of majority of glycolytic, gluconeogenesis, and TCA cycle enzymes (Fba1, Adh1, Hxk2, Tal1, Tdh1,Tdh3, Eno1) thus providing enough acetyl‐CoA for the lipid restructuring and accumulation mechanism since we have found the changes in the cell and mitochondrial lipid content and FA composition. This data suggest that lipids could be the molecules that orchestrate the answer of the cells in the stress response to the Confidor treatment.     

基于网络药理学及分子对接分析丹参黄芪配伍治疗冠心病和心绞痛的活性成分及作用机制

目的：从分子水平研究丹参黄芪配伍抗冠心病和心绞痛的分子机制。方法：采用中药系统药理学数据库和分析平台（Traditional Chinese Medicine Systems Pharmacology，TCMSP）获取丹参和黄芪活性成分，基于CTD （Comparative Toxicogenomics Database，比较毒物基因组学数据库）筛选冠心病和心绞痛的关键靶标。借助STRING软件对心绞痛和冠心病的靶标基因进行相互作用分析，基于分子对接（Sybyl2.1）对筛选所得的丹参、黄芪的活性成分与心绞痛及冠心病靶点进行分子对接验证。借助Cytoscape3.5.1构建"活性成分-靶点"网络模型。结果：丹参黄芪共筛选出61个活性成分，其中丹参44个，黄芪17个。筛选出冠心病靶标25个，心绞痛靶标7个，通过靶蛋白PPI网络分析，肿瘤坏死因子、基质金属蛋白酶-9、Toll样受体4、载脂蛋白E、脂肪酸转运蛋白、血管紧张素Ⅰ转化酶、基质金属蛋白酶-3、尿激酶为冠心病和心绞痛疾病的关键靶标蛋白。分子对接发现黄芪单味药、丹参单味药、黄芪丹参配伍用药可能通过调节尿激酶（PLAU）、载脂蛋白E （APOE）、血管紧张素I转化酶（ACE）发挥抗冠心病及心绞痛的作用。结论：从分子层面筛选丹参黄芪配伍治疗冠心病、心绞痛疾病的关键活性成分及靶点，为其配伍后实验研究和临床应用提供合理解释。