Numerous epilepsy-related genes have been identified in recent decades by unbiased genome-wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation. In this study, we reveal the significant role of KCNQ2 and KCNQ3, two M-type potassium channel genes, in the onset of seizures in TLE. Our investigation began with a quantitative analysis of two publicly available TLE patient databases to establish a correlation between seizure onset and the downregulated expression of KCNQ2/3. We then replicated these pathological changes in a pilocarpine seizure mouse model and observed a decrease in spike frequency adaptation due to the affected M-currents in dentate gyrus granule neurons. In addition, we performed a small-scale simulation of the dentate gyrus network and confirmed that the impaired spike frequency adaptation of granule cells facilitated epileptiform activity throughout the network. This, in turn, resulted in prolonged seizure duration and reduced interictal intervals. Our findings shed light on an underlying mechanism contributing to ictogenesis in the TLE hippocampus and suggest a promising target for the development of antiepileptic drugs.

目的 分析蚌埠及周边地区血脂异常患者有机阴离子转运多肽编码基因SLCO1B1和载脂蛋白E(APOE)基因多态性分布及其临床意义.方法 利用聚合酶链反应(PCR)-荧光探针技术,对2020年7-12月在蚌埠医学院第二附属医院就诊的血脂异常患者1530例外周全血基因组中SLCO1B1和APOE基因多态性进行检测,分析其多态性分布情况并统计不同性别基因型分布差异.结果 蚌埠及周边地区患者APOE各基因型所占比例分别为0.52％(E2/E2)、14.12％(E2/E3)、1.96％(E2/E4)、67.12％(E3/E3)、15.10％(E3/E4)、1.18％(E4/E4).其中APOE基因型中疗效较好基因型占比为14.64％,疗效正常基因型占比为69.08％,疗效较差基因型占比为16.28％.蚌埠及周边地区患者SLCO1B1各基因型所占比例分别为4.90％(*1a/*1a)、30.13％(*1a/*1b)、36.60％(*1b/*1b)、0.59％(*1a/*5)、8.24％(*1a/*15),17.32％(*1b/*15)、0.26％(*5/*5),0.13％(*5/*15),1.83％(*15/*15).SLCO1B基因型中正常肌病风险患者占比为71.63％,中度肌病风险患者占比为26.15％,高度肌病风险患者占比为2.22％.基因型频率观察值符合Hardy-Weinberg遗传平衡,具有群体代表性,各基因型组合在男女患者间的分布比较,差异无统计学意义(P>0.05).结论 蚌埠及周边地区血脂异常患者SLCO1B1和APOE的基因多态性分布和性别无关,同时它们会影响他汀类药物的疗效及不良反应风险.对使用他汀类药物患者SLCO1B1和APOE进行基因多态性分析,能够辅助临床制定最合理的给药方案,并能达到精用药物的目的.

探讨极域电子教室软件在医学机能学实验虚拟仿真教学课堂上的应用.以本学期2019级临床医学两个带教班级为研究对象,在虚拟仿真教学项目中使用极域电子教室软件,以采用班级为实验组,未采用班级为对照组,比较两个班学生测试成绩并对实验组学生发放调查问卷.测试成绩结果显示实验组成绩(98.000±4.549)与对照组成绩(88.807±9.478)比较差异具有统计学意义(P＜0.001).问卷调查结果显示100％的学生表示采用极域软件教学能更有助于学习,75.86％的学生更倾向使用该软件.极域电子教室软件在医学机能学实验虚拟仿真教学课堂中具有积极的促进作用.

目的:研究环巴胺对四氯化碳(CC14)所致肝损伤动物模型的作用效果和影响.方法:清洁级ICR小鼠40只,随机均分为正常对照组(腹腔注射生理盐水)、模型组(腹腔注射CC14,2次/周)、环巴胺预防1组(腹腔注射环巴胺5 mg/(kg·d)+CC14,2次/周)及环巴胺预防2组(腹腔注射环巴胺10 mg/(kg·d)+CC14,2次/周),均续3周.末次给药12 h后,收集小鼠血液和取肝组织做检测.结果:通过生化检测及组织切片染色证实肝损伤模型复制成功.环巴胺预防组生化检测结果均显示血清总胆红素(TBil)、肝组织丙二醛(MDA)水平显著降低(P<0.01),血清总超氧化物歧化酶(T-SOD)活性显著升高(P<0.01);病理结果显示,环巴胺可显著减轻肝细胞变性坏死、肝小叶结构紊乱.结论:环巴胺对CC14所致肝损伤小鼠具有显著保护作用.

目的 探讨PDCA法规范某院氟比洛芬酯注射液用法的效果.方法 分析PDCA法干预前后某院氟比洛芬酯注射液临床的使用情况,总结不合理用药的表现和可能的原因,分析干预后的改进效果.结果 经PDCA法干预后,某院氟比洛芬酯注射液使用的不合理率从整改前的26.47％下降至干预后的11.76％,其中骨科二病区、普外西科等科室的剂量偏大、联合用药、疗程过长等问题明显好转.结论 PDCA法规范某院氟比洛芬酯注射液临床使用效果较好,值得推广.

目的 观察仙灵骨葆胶囊灌胃给药引起大鼠肝损伤的作用及机制研究.方法 将60只SD雄性大鼠随机分为5组:正常组、仙灵骨葆低剂量组[0.27 g/(kg·d)]、仙灵骨葆中剂量组[1.08 g/(kg·d)]、仙灵骨葆高剂量组[2.7 g/(kg·d)]、秋水仙碱组[0.1 mg/(kg·d)],每组12只,连续用药2周后,对血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)和基质金属蛋白酶9(MMP-9)的含量进行分析,并测定肝脏组织匀浆液中的丙二醛(MDA)、超氧化物歧化酶(SOD)的含量及肝组织形态学检查.结果 与正常组相比,仙灵骨葆组大鼠体质量增速显著减缓,肝脏指数降低显著,血清ALT、AST、MMP-9差异显著(P<0.01),肝组织SOD、MDA变化显著(P<0.01),尤以中剂量组较为明显.秋水仙碱组体质量、肝指数、血清及肝组织生化指标均与正常组有显著差别(P<0.01或P<0.05).显微镜下观察到仙灵骨葆组肝细胞排列紊乱,肝细胞有炎性浸润,胞浆疏松、肿胀.结论 仙灵骨葆胶囊对大鼠具有一定的肝损伤作用,大剂量及长期服用应预防其副作用;秋水仙碱因其毒副作用大对在体动物肝脏的作用还有待进一步验证,提示临床服用需提防其肝损伤作用.

OBJECTIVE:To investigate effect of upregulated touch sensation induced by olfactory deprivation on action potentials and ankyrin-G expression in the glutamatergic neurons in the barrel cortex of mice.METHODS:Chloroform (40 μL) was dropped into the unilateral nasal cavity to induce olfactory deprivation in 40 C57 mice (12 days old), whose glutamatergic neurons were genetically labeled with yellow fluorescent protein (YFP). Behavioral experiments were carried out to assess the effects of olfactory deprivation on whisker tactile of the mice. The action potentials of the glutamatergic neurons in the barrel cortex on the side with or without chloroform treatment (olfactory deprivation group and control group, respectively) were recorded by patch-clamp electrophysiological recording, and ankyrin-G expression in the proximal axonal segment of the neurons was detected with immunohistochemistry.RESULTS:Compared with those on the control side, the inter-spike intervals of the barrel glutamatergic neurons were significantly decreased and the absolute refractory periods were significantly shortened on the side with olfactory deprivation (P < 0.01); the expression of ankyrin-G was also significantly increased in the proximal axonal segment of the glutamatergic neurons in the barrel cortex on the side with olfactory deprivation (P < 0.01).CONCLUSIONS:Olfaction deprivation induces up-regulation of touch sensation in mice possibly as a result of functional enhancement of the glutamatergic neurons and increased ankyrin-G expression in the barrel cortex.

目的 观察脂多糖诱导小鼠内毒素血症发生时的心肌损伤情况,及丹参酮ⅡA(TⅡA)对心肌损伤有无预防保护作用,是否与RhoA/Rock(Rho激酶)通路激活有关.方法 雄性8～10周龄C57BL/6J小鼠40只,SPF级,体重(20±2)g,依据随机数字表法将小鼠随机分成空白对照组(CON组)、模型组(LPS组)、丹参酮预处理组(TL组)以及丹参酮组(T组)(n＝10).利用腹腔注射脂多糖(LPS)建立内毒素血症模型.TL组和T组,注射丹参酮10mg/(kg·d)共7d;CON组,LPS组生理盐水等体积注射7d.LPS组、TL组末次注射1h后,腹腔注射LPS(10mg/kg).LPS注射6h后,超声心动图测定小鼠心功能.12h后,心肌组织做HE染色,光镜下观察小鼠心肌形态结构的变化;酶联免疫吸附实验,检测心肌组织白介素-1β(IL-1β)的蛋白水平;蛋白质印迹法(Western blot)检测小鼠心肌组织RhoA和Rock1的蛋白含量.结果 超声心动图结果 表明,与CON组比,LPS组和TL组,心率(HR)、射血分数(EF)、短轴缩短率(FS)、每搏输出量(SV)和心输出量(CO)均下降(P<0.05),与LPS组相比,TL组HR、SV、EF、FS和CO均升高(P<0.05);HE染色显示,LPS组心肌组织横纹模糊,胞浆淡染,有炎细胞浸润,TL组未见心肌组织形态学明显改变;与CON组相比,LPS组心肌组织IL-1β、RhoA和Rock1蛋白含量均升高(P<0.05),与LPS组相比,TL组可以降低IL-1β、RhoA和Rock1蛋白含量(P<0.05).结论 内毒素血症引起的小鼠心肌损伤,在丹参酮ⅡA预处理下,可以降低炎性因子,减轻损伤,其作用可能与抑制RhoA/Rock(Rho激酶)通路激活有关.

目的 复方非那沙星温度敏感型原位凝胶滴耳剂的处方优化.方法 以测定相转变温度为依据,考察不同比例的泊洛沙姆407、泊洛沙姆188、聚乙二醇6000、等基质对于凝胶性状、相转变温度等的影响.以能否获得适宜耳用的相转变温度(34℃左右)为依据,运用正交设计法筛选并确定最优处方.结果 制备成有适宜相变温度的复方非那沙星温度敏感型原位凝胶滴耳剂.结论 本实验确定了制备复方非那沙星温度敏感型原位凝胶滴耳剂的最优处方,且泊洛沙姆407、泊洛沙姆188、聚乙二醇6000三种基质的最佳配比为17％∶3％∶1.5％.

Objective To observe the effect of DI-fu kidney-tonifying granule of TCM on osteoporosis in rats with deficiency of the kidney.Methods 72 female of SD rats were divided into 6 groups:Sham,Model,Positive(dose of 0.27 g·kg-1),High dose group(11.72 g·kg-1)、Medium dose group(5.86 g·kg-1),Low dose group(2.93 g·kg-1)of DI-fu kidney-tonifying granule.There were 12 mice in each group,except the Sham,the remaining groups were executed orariectomy to establish osteoporosis model.After 8 weeks,the results of every group were observed,compared and analyzed.Results DI-fu kidney-tonifying granule of TCM could significantly promote the level of Uterus'index,BMD,Ca2+,E2 on osteoporosis in rats with deficiency of the kidney,reduce the ratio of high divert of bone by decreasing the activity of TLAP and ALP,decrease the expression of IL-6.Conclusion DI-fu kidney-tonifying granule of TCM has effects on osteoporosis in rats with deficiency of the kidney by tonifying the kidney.