目的:研究不同浓度茶色素在高镁条件下对离体蟾蜍心肌收缩力、心率及心电图的影响.方法:72只蟾蜍随机分为对照组和实验组,对照组包括正常任氏液组、茶色素组(200 mg·mL-1和400μg·mL-1)和高镁组(4 mg·mL-1 Mg2+和8 mg·mL-1 Mg2+),实验组分为4 mg·mL-1 Mg2++200或400μg·mL-1茶色素组和8 mg·mL-1 Mg2++200或400μg·mL-1茶色素组.采用斯氏法制备离体蛙心灌流标本,心室外容积固定为1.0mL,每次加药后记录30～40 min,应用BL-420S生物机能实验系统同时记录离体蟾蜍心脏的心肌收缩力、心率及心电图并进行统计分析.结果:在正常任氏液条件下,改灌流400μg·mL-1茶色素时,离体蟾蜍心肌收缩力增强(P<0.05),而心率无显著变化(P>0.05);改灌流高镁任氏液时,离体蟾蜍心肌收缩力和心率显著降低(P<0.05或P<0.01);在高镁条件下,茶色素使离体蟾蜍的心肌收缩力、心率显著提高(P<0.05或P<0.01);与正常任氏液组比较,高镁任氏液组心电图可见P-R间期延长,QRS波群变小增宽,而茶色素可使高镁条件下的异常心电图恢复正常.结论:在高镁条件下茶色素对离体蟾蜍心脏有明显的保护作用.

G protein-coupled receptor 50 (GPR50) belongs to the G protein-coupled receptor which is highly homologous with the sequence of melatonin receptor MT1 and MT2. GPR50 expression has previously been reported in many brain regions, like cortex, midbrain, pons, amygdala. But, the distribution of GPR50 in the hippocampus and cortex and the cell types expressing GPR50 is not yet clear. In this study, we examined the distribution of GPR50 in adult male mice by immunofluorescence. Our results showed that GPR50 was localized in the CA1-3 pyramidal cells and the granule cells of the dentate gyrus. GPR50 was also expressed in excitatory and inhibitory neurons. As inhibitory neurons also contain many types, we found that GPR50 was localized in some interneurons in which it was co-expressed with the calcium-binding proteins calbindin, calretinin, and parvalbumin. Besides, similar results were seen in the cortex. The widespread expression of GPR50 in the hippocampus and cortex suggests that GPR50 may be associated with synaptic plasticity and cognitive function.

There is a need to investigate the role of nuclear factor kappa B in the regulation of cyclooxygenase-2 expression in the epileptic rat brain and cultured hippocampal neurons. Immunofluorescence and polymerase chain reaction was used to detect the expression of nuclear factor kappa B and cyclooxygenase-2. In cultured hippocampal neurons and rat brain: the control group compared with the normal group, nuclear factor kappa B expression in the hippocampal dentate gyrus, cerebral cortex, the piriform cortex brain regions were significantly increased (P < 0.01). This is accompanied by a significant increase in cyclooxygenase-2 protein and mRNA expressions in the hippocampus (P < 0.01). In the experimental group compared to the control group, the nuclear factor-kappa B expression in the hippocampal dentate gyrus, cerebral cortex, piriform cortex, and other brain regions was significantly lower (P < 0.01), with the accompanying decrease in cyclooxygenase-2 protein and mRNA expression (P < 0.01) in the hippocampus. In conclusion, κB-decoy can inhibit nuclear factor kappa B activation in epileptic rat brain and cyclooxygenase-2 overexpression.

将教学模式改革与学生能力培养紧密结合,建立以能力培养为核心的机能实验教学体系,不断完善教学方法并建立与之配套的形成性考核体系及教材体系.以本科医疗专业5年制学生机能实验教学内容为基本框架,针对不同专业、不同层次学生,运用多种教学方法,建立了多元化的教学模式.并形成人才培养的金字塔模式:学生通过由具备实践能力→综合素质→创新精神的培养过程,将教学模式改革与学生能力培养紧密结合.实践表明,对医学生动手操作能力、解决问题及分析问题能力、创新能力、自主学习能力的培养均起到了良好的促进作用.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient (Chst14−/−) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14−/− mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14−/− mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14−/− mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

目的 研究高压氧对急性一氧化碳中毒大鼠心肌损伤的保护作用.方法 将大鼠随机分为正常对照组(NC组),急性一氧化碳中毒组(CO-P组),高压氧治疗组(HBO组).采用分次腹腔注射法建立急性一氧化碳中毒大鼠模型,对照组大鼠腹腔注射同等剂量空气,高压氧组大鼠给予高压氧治疗15天,每天1次.CO-P组和HBO组于CO染毒前,第1、2、3、4次CO注射术后1h,第3、7、15天,描记心电图.于染毒后第1天和第16天应用电镜观察各组大鼠心肌超微结构改变.结果 心肌超微结构:CO-P组第1天可见心肌纤维排列紊乱,线粒体肿胀等现象;第16天线粒体腔和嵴间隙略增大.HBO组第1天可见线粒体呈轻度肿胀改变等现象,第16天超微结构已恢复正常.ECG:与NC组比较,CO-P组第4次CO注射后1h、第3、7天和HBO组第3天ST段分别抬高(0.34±0.16)mv,(0.27±0.18)my,(0.20±0.08)my,(0.21±0.11)mv(P ＜0.01);与CO-P组第4次CO注射后1h比较,CO-P组第3、7、15天和HBO组第3、7、15天ST段均显著降低(P＜0.01);与NC组比较,CO-P组第15天和HBO组第7、15天ST段改变基本恢复(P＞0.01).结论 HBO可以显著减轻CO-P大鼠心肌超微结构的损伤程度;CO-P大鼠心电图ST段改变都是可逆的,高压氧治疗可加速ST段下降持续时间及ST段下降幅度,加快心肌损伤的恢复,对心脏有明显的保护作用.

Introduction:Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior. Methods:We evaluated 21-day-old BALB/c mice with and without isolation for aggressive behavior using a resident-intruder test. Immune-reactivity and protein expression of ADAR1 (p110) were measured using immunohistochemistry and Western blotting. Htr2c RNA editing was evaluated using pyrosequencing. In addition, the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 was used to treat the isolated mice, and the performance of both treatments on the behavior, ADAR1 (p110) expression, and Htr2c RNA editing in isolated mice was examined. Results:Both the protein expression and immune-reactivity of ADAR1 (p110) in the amygdala decreased, but the percentage of Htr2c RNA editing at A and B sites of amygdala only showed a moderate increase in isolated BALB/c mice with enhanced aggressive behavior compared to the age-matched group-housed BALB/c mice. Additionally, treatment with the 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered the enhanced aggressive behavior of isolated mice and returned the protein expression and immune-reactivity of ADAR1 (p110) back to the normal level. Moreover, compared to the age-matched isolated mice treated with physiological saline, isolated mice treated with 5-HT 2C R inverse agonist SB206553 showed a lower percentage of Htr2c RNA editing at both A and B sites, and the same result occurred in isolated mice treated with 5-HT 2C R antagonist SB243213 at B site of Htr2c RNA editing. Conclusions:The 5-HT 2C R antagonist SB243213/5-HT 2C R inverse agonist SB206553 recovered increased aggressive behavior of isolated BALB/c mice mediated by ADAR1 (p110) expression and Htr2c RNA editing.

随着现代医学模式的转变,医学人文教育与医学专业教育的融合已成为医学教育主体构成的重要组成部分.医学基础实验教学是进行人文知识教学的绝佳阵地,在实验教学中运用多种教学方法、整合并丰富实验教学内容、提高教师的人文素质、营造医学人文文化氛围等方面,来探讨如何将医学人文素质教育融于实验教学中及二者融合在医学基础实验教学中的实际效果.

Objective To observe the influence of tea pigment on myocardial contractility,electrocardiogram(ECG) and heart rate in exsomatized toads under the condition of myocardialischemia.Methods Sixty toads were divided into the normal exsomatized toad heart group(A) and myocardial ischemia toad heart(B).Then the group A was re-divided into the Ringer's solution group (A1),tea pigment low dose(200 mg/L) group(A2) and the high dose(400 mg/L) group(A3);the group B was re-divided into the pituitrin model group(B1),pituitrin + tea pigment low dose(200 mg/L) group(B2) and high dose(400 mg/L) group(B3).The BL-420S biological function experiment system was used to record the myocardial contractile force and ECG change curve of exsomatized toad.Results Compared with the group A1,the myocardial contractility in the group A3 was obviously increased(P＜0.05),the difference in the group A2 had no statistical significance(P＞0.05);the QRS peak value of ECG and heart rate had no statistically significant difference(P＞0.05);compared with the group A1,the myocardial contractility,ECG QRS peak value and heart rate in the group B1 were significantly decreased(P＜0.05);compared with the group B1,the myocardial contractility,ECG QRS peak value and heart rate in the group B2 and B3 were significantly increased(P＜0.05).Conclusion Tea pigment can obviously improve the decrease of the exsomatized toad cardiac activity caused by myocardial ischemia.

Genipin is the major active component of Gardeniae fructus and has been shown to ameliorate diabetes and insulin resistance in rat models. In this study, we first investigated the effect of genipin on obesity and the related lipid metabolism mechanisms in diet-induced obese rats. Our results showed that genipin reduced body weight, food intake, and visceral fat mass; ameliorated dyslipidemia, glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic steatosis; and reduced serum tumor necrosis factor- level in diet-induced obese rats. Quantitative real-time reverse-transcription polymerase chain reaction results further illustrated that genipin promoted lipolysis and -oxidation of fatty acid by upregulating gene expressions of hormone-sensitive lipase and adipose triglyceride lipase in white adipose tissue (WAT) and peroxisome proliferator-activated receptor- and carnitine palmitoyltransferase 1 in hepatic tissue. Moreover, genipin promoted browning of WAT by upregulating the mRNA and protein levels of uncoupling protein 1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis factor-, and interlukin-6 in WAT. These results indicated that genipin had a potential therapeutic role in obesity, in which regulation of lipid mobilization and browning of WAT were involved.

实验中心将平台建设紧密结合学科的定位与发展规划,建立大学生创新实验基地及人体实验室 、虚拟实验平台 、自主学习平台 、移动学习平台,构建了集教学科研为一体的多元化 、多功能实验平台.将平台建设与教学模式改革有机结合,"以学生为本,以能力培养为核心",设置层层递进 、不断提高的实验课程模式,优化实验教学体系,加强实验室整合和资源配置,有效推动了医学实验教学管理与教学方法改革,使高等医学教育更好地体现了人才培养的质量要求.

In order to carry out the training objectives of " excellent doctor education and training program" and to implement the teaching model of " preclinic medical education and the vertical organ-system oriented integrated curriculum",in the preclinic medical learning period,Basic Medical School of Dalian Medical University has constructed a progressive and continuous improved preclinic medical experimental teaching system characterized in "system,comprehension,design and creation" for clinical medical students of five-year system of clinicál medicine specialty.The medical practice ability and preliminary clinical diagnostic thinking ability of medical students can be developed by the path of the basic and comprehensive experiments.The students' innovative thinking and scientific research ability can be cultivated gradually through the course of innovation which is included in the teaching plan as a limiting election one.After nine semesters of exploration and practice,the results indicate that this new developing experimental teaching model is helpful for medical students to train their ability in preclinic medical knowledge and skills,comprehensive analysis,and innovation,and suits the need of five-year clinical medical talent training model from "excellent doctor education and training program".And the results may lay the foundation to explore and establish an ‘ 5 + 3 ’ clinical medical talent training model,deepen the clinical medicine education reform of seven-year-system,and cultivate tiptop innovative medical talents.

ObjectiveTo explore the effects of social isolation on the cognition and expression of 5-HT2C receptor(5-HT2CR) and adenosine deaminase that act on RNA 1(ADAR1) in BALB/c mice.MethodsThe healthy BALB/c mice were isolated for 2,4,and 8 weeks individually since postnatal 21 days respectively to set up isolation mice model,the same age mice without isolation were regarded as control group.The new object location and the new object recognition tests were used to measure the spatial and non-spatial cognitive function,and western blot was used to measure the protein expression of 5-HT2CR and ADAR1.ResultsThe new object location test showed that the spatial discrimination index (DI) of BALB/c mice isolated for 2 weeks was decreased significantly compared with the control group(control group was (0.075±0.340),isolation group was (-0.653±0.308),P<0.05),and no obvious difference was found for the group isolated for 4 and 8 weeks.The new object recognition test showed that the non-spatial DI of BALB/c mice isolated for 2 and 4 weeks were decreased significantly compared with the control group(control 2 weeks group was (0.088±0.210),isolation 2 weeks group was (-0.945±0.194),P<0.05;control 4 weeks group was (0.105±0.267),isolation 4 weeks group was (-0.506±0.215),P<0.05),and no obvious difference was found for the group isolated for 8 weeks.Compared with the control group the expression of 5-HT2CR and ADAR1 in the hippocampus were decreased significantly for the group isolated for 2 weeks.(5-HT2CR:control group was (1.025±0.144),isolation group was (0.891±0.026),P<0.05.ADAR1: control group was (0.839±0.120),isolation group was (0.629±0.094),P<0.05).ConclusionsTwo week social isolation results in the decrease of spatial and non-spatial cognitive function in BALB/c mice,in the meanwhile,social isolation stress results in the obvious decrease of 5-HT2C receptor and ADAR1 protein expression in the hippocampus of BALB/c mice.

OBJECTIVE To formulate resibufogenin (RBG)-loaded polylactide-co-glycolide-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (RPTN) with RBG as model drug and PLGA TPGS as polymer matrix,the best prescription and preparation technology of nanoparticles were chosen by orthogonal tests,in vitro stability of RPTN was evaluated.METHODS RPTN was prepared by the ultrasonic emulsification-solvent evaporation method.The determination of the best prescription and preparation technology of nanoparticles:influence on preparative conditions (such as size,drug loading and entrapment efficiency) with different ratios of RBG to polymer matrix,different concentrations of TPGS aqueous solution,different ultrasonic power and time were estimated by appraisal method.Then factors and levels of the orthogonal design were established and the best prescription and preparation technologies of nanoparticles were selected.The in vitro stability of RPTN was examined by the stress testing,acceleration testing and long term testing.RESULTS According to orthogonal tests,the best prescription and preparation technologies of RPTN were selected:3∶10 (W∶W) was selected as the best ratio of RBG to PLGA-TPGS with 0.05％ TPGS aqueous solution as emulsifier,then the mixed solution was sonicated for 10 min at 250 W.The average particle size,DL and EE of RPTN were (152.3 ± 2.5) nm,(18.4 ± 0.3) ％ and (79.3 ±-1.2) ％ (n =6),respectively.The nanoparticles showed good stability under the conditions of the stress testing,acceleration testing and long term testing.CONCLUSION The best prescription and preparation technologies of RPTN are selected.RPTN produces smaller particle size,higher DL and EE,and good in vitro stability.

目的 观察茶色素(TPs)预处理对心肌缺血离体蟾蜍心肌收缩力、心率和心电图的影响.方法 选取50只蟾蜍随机分为对照组和实验组.对照组分为任氏液组和模型组.实验组分TPs预处理低、中和高剂量(200 mg/L、400 mg/L和800 mg/L)+垂体后叶素组.应用BL-420S生物机能实验系统同时记录离体蟾蜍心肌收缩力和心电图曲线,并进行心肌收缩力、心率和心电图的统计学分析.结果 垂体后叶素组与任氏液组比较,心肌收缩力、心率和心电图QRS波峰值均明显减小(均P<0.05),心电图T波峰值明显增大(P<0.001).灌流垂体后叶素与灌流不同浓度TPs比较:心肌收缩力,TPs为200 mg/L略有减小,差异无统计学意义(P>0.05),TPs为400 mg/L和800 mg/L时明显增加(P<0.05);心率略有变化,但差异无统计学意义(P>0.05);心电图,QRS波幅和T波峰值略有变化,差异无统计学意义(P>0.05).结论 一定浓度的TPs能预防由垂体后叶素引起的离体蟾蜍心脏活动低下.

The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)- induced acute liver and renal damages have been reported in our previous works. However, the actions of dioscin against LPS-induced acute lung injury (ALI) is still unknown. In the present study, we investigated the effects and mechanisms of dioscin against LPS-induced ALI in vitro and in vivo. The results showed that dioscin obviously inhibited cell proliferation and markedly decreased reactive oxidative species level in 16HBE cells treated by LPS. In addition, dioscin significantly protected LPS-induced histological changes, inhibited the infiltration of inflammatory cells, as well as decreased the levels of MDA, SOD, NO and iNOS in mice and rats (p < 0.05). Mechanistically, dioscin significantly decreased the protein levels of TLR4, MyD88, TRAF6, TKB1, TRAF3, phosphorylation levels of PI3K, Akt, IκBα, NF-κB, and the mRNA levels of IL-1β, IL-6, and TNF-α against oxidative stress and inflammation (p < 0.05). Dioscin significantly reduced the overexpression of TLR4, and obviously down-regulated the levels of MyD88, TRAF6, TKB1, TRAF3, p-PI3K, p-Akt, p-IκBα, and p-NF-κB. These findings provide new perspectives for the study of ALI. Dioscin has protective effects on LPS-induced ALI via adjusting TLR4/MyD88- mediated oxidative stress and inflammation, which should be a potent drug in the treatment of ALI.

Virtual simulation experiment teaching can effectively reduce the experimental cost,widen the beneficial scope,and solve the problem of high quality experimental resource sharing.Starting from the background and significance of the construction of virtual simulation experiment teaching center,combined with the construction experience of virtual simulation experiment teaching center of Dalian Medical University, around the construction of autonomous learning platform,4A network teaching and digital network teaching resources, this paper discusses the current structure of the experimental teaching center of virtual simulation,system function and the existing problems in the construction.

我国高等教育的重要意义就是培养高素质的人才,创新能力是人才培养质量中的关键性指标之一.通过医学机能学创新性实验的推动,大力开展大学生创新能力训练,基本形成了基于机能实验学课堂教学配合各层次科研活动的立体互动式科研能力培养模式并初见成效.对于促进学生全面发展和改进教学方法具有重要意义.

OBJECTIVE:To study the inhibitory effects of sinomenine(SIN)-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate(PLGA-TPGS)nanoparticles(SPTN)on the proliferation of HCa-F cells in lymph tubes and ec-topic transplantation tumors in mice. METHODS:HCa-F cell suspension were incubated with normal saline,5-fluorouracil(FS), sinomenine solutions (SS),sinomenine PLGA nanoparticles (SPN) and SPTN,with concentration of 80 μg/ml. The cells were marked with CFSE,and then were injected with suspension 50 μl via one footpad of mice. Inhibitory effect of above suspensions on the proliferation of HCa-F in lymph tubes of mice was observed by fluorescence inverted microscope at 3,6,9,12,24 h(n=15). Mice were divided into normal control group,blank PLGA-TPGS nanoparticles (EPTN) group,normal saline group,SPTN group,SPN group,SS group and FS group with 10 mice in each group. The latter 5 groups were injected with relevant medicine 15 mg/kg,once a day,via tail vein for consecutive 10 days after the model of HCa-F cells-bearing ectopic transplantation tumor mice was established. The serum content of ALT,AST,γ-glutamyltransferase(γ-GT),ALB and T-BIL were determined;solid tu-mors were taken,measured and weighed,and the inhibitory rate of tumor was also calculated. RESULTS:The inhibitory effect of above solution on the proliferation of HCa-F cells in descending order was as follows:SPTN>SPN>FS>SS>normal saline. Com-pared with normal saline group,the serum levels of ALT,AST,γ-GT and TBIL of SPTN group,SPN group,SS group and FS group decreased,while ALB level increased(P<0.05);the amount of tumor volume increase and tumor weight in SPTN group, SPN group and FS group decreased significantly (P<0.05). The inhibitory rate of tumor in 3 groups were 49.62%,40.53% and 33.90%. CONCLUSIONS:SPTN can inhibit the proliferation of HCa-F cells in lymph tubes of mice,and can improve HCa-F cells-bearing ectopic transplantation tumor in mice. It is better than SPN and FS.

A lot of literature show that social isolation stress could be a key reason that leads to cognitive deficits for both humans and rodent models; however, the detailed mechanisms are still not clear completely. ADAR1 (Adenosine deaminase acting on RNA) is an enzyme involved in RNA editing that has a close relation to cognitive function. We hypothesize that social isolation stress may impact the expression of ADAR1, leading to cognitive deficits. To prove our hypothesis, we evaluated the cognition ability of the mice isolated for different durations (2, 4, and 8 weeks) using object recognition and object location tests; we also measured ADAR1 expressions in hippocampus and cortex using immunohistochemistry and western blot. Our study showed that social isolation stress significantly induced spatial and non-spatial cognition deficits. In addition, social isolation significantly increased both the immuno reactivity and protein expressions of ADAR1 in the hippocampus and frontal cortex. Furthermore, we found that adolescent re-socialization recovered not only the cognition deficits but also the increased ADAR1 protein expression in hippocampus and the increased number of ADAR1 positive cells in frontal cortex of the isolated mice. In conclusion, social isolation stress significantly increased ADAR1 expressions in the hippocampus and cortex, leading to cognitive deficits.