百草枯对小鼠的急性毒性试验

目的 观察百草枯(Paraquat,PQ)对小鼠的急性毒性,计算其半数致死量(LD50).方法 给小鼠灌服不同浓度的PQ溶液,通过观察小鼠的活动和毒性反应,记录小鼠的死亡数,用概率单位法计算LD50.结果 给药后不同时间内,小鼠出现自由活动减少,濒死时呼吸频率加快、张口呼吸、鼻翼扇动等中毒症状,死亡高峰在2 h内,死亡原因为多脏器损伤.♂小鼠LD50=106.99 mg·kg-1,95%可信限范围为97.01～118.03 mg·kg-1;♀小鼠LD50=86.40 mg·kg-1,95%可信限范围74.54～100.14 mg·kg-1.结论 PQ属于中等毒农药,♀小鼠更敏感.     

The −22c/t polymorphism in presenilin 1 gene is not connected with late-onset and early-onset familial Alzheimer’s disease in Poland

Summary. The –22c/t polymorphism in the promoter of the presenilin 1 gene is associated with increased risk for Alzheimers disease (AD) in some populations. It was shown that –22c allele is connected with two-fold decrease in promoter activity. We studied the impact of the polymorphism in groups of Polish late-onset and early-onset AD patients. Our results suggest that –22c/t polymorphism is not connected with AD in Polish population. The –22t allele showed a high degree of linkage disequilibrium with –2797 insertion of 13bp. An additional –2923g/t polymorphism is also not connected with –22c/t and is not a risk factor for AD.     

机器人辅助腹腔镜全子宫切除治疗巨大子宫肌瘤伴盆腔复杂粘连：附1例报告

目的报告机器人辅助腹腔镜全子宫双侧输卵管切除治疗巨大子宫肌瘤伴盆腔复杂粘连患者l例，结合文献讨论该病的临床症状、手术术式及机器人手术的优势。方法患者1998年体检发现子宫肌瘤后未予治疗，定期复查提示肌瘤逐渐增长。超声提示多发子宫肌瘤，盆腔MRI提示巨大子宫肌瘤伴出血。结果完善相关检查后行机器人辅助腹腔镜全子宫+双侧输卵管切除术，手术进展顺利，患者术后4 d出院，腹壁美观，随访恢复良好。结论机器人辅助腹腔镜因其特有的优势，为巨大子宫切除伴盆腔复杂粘连患者提供了微创手术入路选择。     

来自不同地域的新护士职业综合素质调查分析与对策

目的:了解医院来自不同地域新护士职业综合素质情况,寻找有效应对管理方法,保障临床护士身心健康。方法:采用自行设计的职业综合素质问卷调查表,对本院176名新护士进行调查。结果:本地与外地临床新护士对从事职业主观态度方面无显著性差异P>0.05,在学历、职称、家庭经济、人均月收入有显著性差异P<0.01,掌握知识、技能、应急处理突发事件等方面无显著性差异P>0.05,对职业满意度尤其是同工同酬方面有显著性差异P<0.01。结论:一视同仁对待每一位护士,重视护理工作中的激励因素,满足新护士目标实现的高层次需求,帮助新护士正确选择职业发展道路,培养新护士创新性思维,是实现现代化管理、提升护理质量的有效举措。     

Inhibitory effects of Geijigajakyak-Tang on trinitrobenzene sulfonic acid-induced colitis

Aim of the study

Water extract of Geijigajakyak-Tang (GJT) consisting of five crude drugs [dried root of P. lactiflora Peony (Paeoniaceae), dried trunk bark of C. cassia Blume (Lauraceae), seed of Z. jujube var. inermis Mill (Rhamnaceae), fresh root of Z. officinale Rocoe (Zingiberaceae) and dried trunk bark of G. uralensis Fish (Leguminosae)] is a folk medicine used for the treatment of chronic colitis. This study was designed to further elucidate the effect of GJT on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats.

Materials and methods

GJT orally given to mice before and after TNBS intoxication, and their clinical and morphological changes, myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels in colon tissues, were evaluated on Day 8 post-TNBS. Furthermore, the effect of six major constituents of individual herbs on ileum smooth muscle contraction and neutrophil chemotaxis was studied.

Results

GJT had a significant anti-inflammatory effect based on clinical and morphologic changes, MPO activity and MDA levels in colon tissues as compared with sham control. GJT and 5 major active constituents of individual herbs, paeoniflorin, cinnamaldehyde, jujuboside A, jujubogenin, and diammonium glycyrhhizinate significantly inhibited neutrophil chemotaxis. GJT significantly inhibited muscle contraction (IC₅₀; 2.10 ± 0.11 mg/ml), and 1,8-cineol has the most spasmolytic activity (IC₅₀; 0.10 ± 0.03 mg/ml).

Conclusion

GJT has significant anti-inflammatory effects on TNBS-induced colitis via inhibitions of smooth muscle contraction and neutrophil chemotaxis.     

孤独症谱系障碍儿童的血清胰岛素样生长因子-1和胰岛素样生长因子结合蛋白-3水平研究

目的探讨孤独症谱系障碍（autism spectrum disorder，ASD）儿童的血清胰岛素样生长因子-1（insulin-like growth factor-1，IGF-1）和胰岛素样生长因子结合蛋白-3（insulin-like growth factor binding protein-3，IGFBP-3）水平及与孤独症核心症状之间的关系。方法前瞻性选取重庆市妇幼保健院门诊招募的150名2~7岁ASD 儿童和165名年龄、性别相匹配的正常健康儿童为研究对象，采用孤独症行为量表和孤独症评定量表评估ASD儿童核心症状，采用化学发光法检测两组儿童血清IGF-1和IGFBP-3水平。结果ASD组儿童血清IGF-1水平低于对照组儿童（P<0.05）。重度ASD儿童血清IGF-1和IGFBP-3水平低于轻-中度ASD儿童（P<0.001），2~3岁ASD儿童血清IGF-1水平低于对照组儿童（P<0.05）。两组男童IGF-1水平均低于女童（P<0.05）。血清IGF-1、IGFBP-3水平与儿童孤独症评定量表总分呈负相关（分别r=-0.32、-0.40，均P<0.001）。结论儿童早期血清IGF-1降低可能与ASD疾病发展相关，血清IGF-1和IGFBP-3水平与ASD儿童核心症状具有一定关联。     

Distribution and localization of microfilament cytoskeleton is regulated by EBP50

Objective： To explore the influence of EBP50 （ezrin-radixin-moesin-binding phospho-protein-50） on microfilament cytoskeleton content and distribution in cultured Hela cells, and to investigate the relationship between the changes in microfilament cytoskeleton localization and EBP50 after PDGF （platelet-derived growth factor） stimulation, and to further clarify the molecular mechanism by which EBP50 suppresses tumor cell proliferation and migration. Methods： pBK-CMV-HA- EBP50 wild type recombinant plasmid and pBK-CMV-HA empty vector were transfected into Hela cells. G418 at 350 mg/L was used to screen for cell clones stably expressing EBP50. Western blot was carried out to detect EBP50 expression. Similarities and differences in microfilament cytoskeleton content and distribution in Hela cells transfected with pBK-CMV-HA-EBP50 wild type recombinant plasmid and pBK-CMV-HA empty vector were also treated with PDGF （10 ng/mL and 20 ng/mL, 37 ℃, 15 min） and stained by rhodamine-labeled phalloidin to observe the distribution of microfilament cytoskeleton in the two groups. EBP50 protein distribution in PDGF-stimulated Hela cells was detected by immunofluorescence. Results： Western blot results confirmed that the EBP50 cDNA fragment could express EBP50 in cultured Hela cell lines and that cell lines stably expressing EBP50 were successfully obtained. Western blot and fluorescence results showed that in the cell line transfected with empty vector, the microfilament cytoskeleton was thick, loose, multidirectional and displayed crossing arrangements. The content of microfilament cytoskeleton in the cell line transfected with pBK-CMV-HA-EBP50 was different from that found in the cell line transfected with empty vector. EBP50 expression enhanced microfilament cytoskeleton polymerization into compact thin filaments. Under the stimulation of PDGF, EBP50 migrated to the cell membrane from the cytosol together with microfilament cytoskeleton and co-localized there. Conclusion： EBP50 can change the distributi     

浸润性肺腺癌EGFR、ALK基因突变状态与影像学、病理学特征的相关性

背景与目的当前针对肺腺癌表皮生长因子受体(epidermal growth factor receptor, EGFR)与间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)基因突变位点的靶向治疗研究进展十分迅速，为晚期肺腺癌患者的治疗带来新的希望，然而目前EGFR、ALK基因突变在腺癌患者中所具有的特异性影像学与病理学特征仍存在较多争议，本研究进一步探索浸润性肺腺癌EGFR、ALK基因突变与影像学、病理学特征的相关性。方法纳入2018年1月-2019年12月在我们中心接受手术的525例肺腺癌患者。根据术后基因检测的结果将患者分为EGFR基因、ALK基因突变组与野生组，并将EGFR基因突变组分层为外显子19、外显子21突变亚型，将突变组与野生组的病理学特征如组织学亚型、淋巴结转移、脏层胸膜侵犯(visceral pleural invision, VPI)等，影像学特征如肿瘤最大直径、实性成分占比(consolidation tumor ratio, CTR)、分叶征、毛刺征、胸膜牵拉征、空气支气管征、空泡征等进行单因素分析及多因素逻辑回归分析，探讨基因突变组是否具有特异性表现。结果EGFR基因突变组常见于女性(OR=2.041, P=0.001)，存在更多胸膜牵拉征征象(OR=1.506, P=0.042)，病理学上与淋巴结转移及VPI相关性较小(P > 0.05)。其中外显子21突变型腺癌多见于年龄相对较大者(OR=1.022, P=0.036)及女性(OR=2.010, P=0.007)，常伴有较大肿瘤直径(OR=1.360, P=0.039)及胸膜牵拉征(OR=1.754, P=0.029)。外显子19突变型腺癌常见于女性(OR=2.230, P=0.009)、肿瘤实性成分比例较高(OR=1.589, P=0.047)、存在更多分叶征(OR=2.762, P=0.026)。ALK基因突变易发生于有吸烟史(OR=2.950, P=0.045)及较年轻患者(OR=1.070, P=0.002)，病理学上存在更多微乳头型成分(OR=4.184, P=0.019)及VPI(OR=2.986, P=0.034)。结论EGFR、ALK基因突变型腺癌具有特异的影像学及临床病理学特征，且EGFR外显子19或21突变具有不同的影像学特征，对制定肺结节临床处理策略具有重要意义。     

补肾化痰方治疗多囊卵巢综合征的作用机制：基于网络药理学和分子对接方法

目的探究补肾化痰方治疗多囊卵巢综合征的主要活性成分、靶点、通路等药理学作用机制。方法通过中药系统药理学数据库与分析平台（TCMSP）筛选出补肾化痰方中药物的主要活性成分，使用PubChem和Swiss Target Prediction预测活性成分相关作用靶点；应用GeneCards、OMIM筛选治疗疾病多囊卵巢综合征的作用靶点；将药物靶点与疾病靶点通过Uniprot校正后，取交集靶点；结合STRING构建蛋白-蛋白互作（PPI）网络，并利用Cytoscape3.7.2中的CytoNCA插件对交集靶点进行PPI分析，筛选出核心靶点；采用DAVID数据库进行基因功能GO富集分析和KEGG通路富集分析；利用AutoDock对补肾化痰方中的核心活性成分和核心靶点进行分子对接验证。以动物实验进行验证，24只SPF级雌性C57BL/6J小鼠按随机数字表法分为3组：对照组[n=8，1 mg/（kg·d）生理盐水灌服35 d]，模型组[n=8，1 mg/（kg·d）来曲唑溶于1%羧甲基纤维素（CMC）中，连续灌服35 d，并予高脂饲料喂养]，治疗组[n=8，造模后予以1 mg/（kg·d）补肾化痰方颗粒剂溶于5%生理盐水中，连续灌服35 d]。小鼠末次给药后，取卵巢组织于-80 ℃保存，Western blot法检测小鼠卵巢组织中核心靶点和核心通路的表达。结果补肾化痰方中14味中药共筛选出125个潜在活性成分，990个药物靶点，4759个PCOS靶点，药物与PCOS交集靶点434个；核心活性成分主要为β-谷甾醇、山奈酚、槲皮素等，核心靶点主要为PIK3CA、PIK3R1、APP、AKT1、MAPK1等；GO功能富集主要包括药物反应、凋亡过程的负调控、RNA聚合酶Ⅱ启动子转录的正调控等；KEGG富集通路主要包括癌症通路、HIF-1信号通路、Rap1信号通路、PI3K-Akt信号通路等；分子对接结果显示核心活性成分β-谷甾醇、山奈酚、槲皮素与核心靶点PIK3CA、PIK3R1、APP、AKT1、MAPK1均有强烈的结合能力；动物实验结果表明，补肾化痰方能明显改善多囊卵巢综合征相关症状，并下调PI3K，AKT蛋白表达，上调MAPK1蛋白表达，验证了网络药理学的部分预测结果。结论揭示了补肾化痰方多成分、多靶点、多途径的作用特点，预测并通过实验初步验证了补肾化痰方治疗多囊卵巢综合征的可能作用机制。