Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis

Summary— Acidosis affects multiple steps in the excitation-contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca²⁺ and 3) endothelin-1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady-state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin-1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca²⁺, which was more effective than increasing [Ca²⁺]_i through elevating extracellular Ca²⁺ or the addition of forskolin which increased [Ca²⁺]_i but desensitized the myofilaments to Ca²⁺.     

我国医疗保障制度改革中医院配套改革措施探讨

论述了医疗保障制度改革给医院带来的机遇与挑战,认为医院应采取调整结构,转换运行机制;完善补偿机制;加大宏观调控力度,制订和实施区域卫生规划等配套措施,来适应医疗保障制度的改革。     

conference report: Mental health and intellectual disability: an international perspective

The present paper reports on the inaugural meeting of the Mental Health Special Interest Research Group (SIRG) of the International Association for the Scientific study of Intellectual disability which was held at Fitzwilliam College, Cambridge, UK, in March 1998. The meeting was organized in conjunction with the Ninth Annual SIRG on ageing and intellectual disability. Representatives from North America, several European and Scandinavian countries, Australia, and Israel attended. Two broad themes had been determined prior to the meeting: ‘Improving the detection of mental health problems’ and ‘Research strategies for identifying risk factors for mental health problems’. In the presentations and subsequent discussions, it was apparent that there were extrenely diverse perspectives both across and within the different countries represented. Not only were individuals' experiences very different, but most strikingly, the theoretical frameworks were very diverse. This was partly a function of there being understandable differences in perspectives across disciplines, but at its most marked, there were fundamental differences in the way both intellectual disability and mental health were conceptualized.     

我国农村订单定向医学生培养的研究热点与趋势分析

背景 农村订单定向医学生（简称定向医学生）的免费培养工作是缓解农村地区基层医生匮乏、提升基层医疗卫生队伍整体素质和水平的重要举措。目的 探索我国定向医学生培养的研究热点、研究动态和未来趋势,为后续研究提供参考。方法 于2022-02-15,在中国知网、万方数据知识服务平台、维普网中检索2010-01-01至2021-12-31发表的关于定向医学生培养相关论文,统计其发文量,运用Cite Space软件对样本文献作者、研究机构、关键词进行知识图谱的可视化分析。结果 共纳入598篇文献,关于定向医学生培养研究的文献量呈上升趋势,2018年达到历年顶峰（n=81）。该领域存在5个大的作者群,发文量排在前3位的机构为赣南医学院[113篇（18.9%）]、广西医科大学[40篇（6.7%）]及新乡医学院[28篇（4.7%）]。关键词词频排在前3位的分别是“订单定向”（70次）、“定向生”（57次）、“人才培养”（44次）。关键词聚类图谱得到“#0学习动力”“#1教学模式”“#2定向培养”“#3影响因素”“#4全科医学”“#5基层”“#6医学院”“#7医学生”8个聚类主题。最强突现词显示,排在前3位...     

小儿遗尿症指南和专家共识质量评价

背景 小儿遗尿症是儿科常见病之一,有效的小儿遗尿症诊疗指南有助于症状的规范化控制和缓解,而制定高质量的临床实践指南是提高小儿遗尿症诊疗水平的重要方式。目的 基于AGREEⅡ和RIGHT工具,评价2010年以来国内外发布的小儿遗尿症指南和专家共识的质量,以期为临床实践及后续指南的制订提供参考。方法 检索中国知网、万方数据知识服务平台、维普网、中国生物医学文献数据库和PubMed(补充检索医脉通、世界卫生组织以及英国国家临床示范研究所等数据库)2010-01-01至2022-01-31公开发表的小儿遗尿症相关的诊疗指南和专家共识。采用AGREEⅡ和RIGHT工具评价纳入文献的方法学和报告质量。根据AGREE Ⅱ工具评价结果,将各指南/共识推荐等级评定为“推荐(A级)”“更新后推荐(B级)”和“不推荐(C级)”。使用组内相关系数(ICC)进行一致性评价。结果 纳入8部指南和5部专家共识。共形成推荐意见185条,其中44条为诊断评估方面的意见,140条为治疗方面的推荐意见,1条为随访推荐意见。AGREEⅡ工具评价结果显示,范围和目的、参与人员、严谨性、清晰性、应用性和独立性6个领域的总得分(报...     

中医药治疗子宫内膜息肉的临床研究进展

子宫内膜息肉是妇科常见疾病,现代中医认为本病主要病理因素是瘀滞,临床常见气滞血瘀、痰湿瘀阻、湿热瘀滞、气虚血瘀、阳虚血瘀诸证,运用中医药辨证治疗、中医外治法,可有效改善临床症状,降低息肉复发率,提高妊娠率。本文将近十年中医药治疗子宫内膜息肉的临床研究作以综述。     

Cytogenetic characterization of ten cases of Ph1-positive acute myelogenous leukemia

Chromosome banding analyses were made on 10 cases of Ph1-positive AML (7 M1 and 3 M2). The standard type Ph1 translocation, t(9q +;22q -), was identified in all of them. Karyotypically normal cells were observed in 6-65% of bone marrow metaphases at the initial cytogenetic examination of 7 patients, whereas the remaining 3 patients had only Ph1-positive cells at diagnosis. Follow-up studies performed in 5 cases indicated that the frequency of karyotypically normal cells increased up to 81-100% when the patients were in remission, whereas it was much reduced in relapse. In 5 cases, there was observed a clone of cells in which the Ph1 translocation was the sole karyotypic abnormality. Various types of other chromosome abnormalities, in addition to the Ph1, were observed in all cases, among which-7 was the most frequent, being found in three cases as a stem line. Other additional changes encountered were + Ph1, del(5), i(17q), - 10, + 18, + X, and various numerical and structural changes including certain secondary translocations that occurred in the Ph1 (22q -) or its partner (9q +). The types and frequencies of these additional changes appeared to be different from those found in the acute phase of CML or in Ph1-positive ALL.     

Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage

Although gross insertions (>20 bp) comprise <1% of disease-causing mutations, they nevertheless represent an important category of pathological lesion. In an attempt to study these insertions in a systematic way, 158 gross insertions ranging in size between 21 bp and approximately 10 kb were identified using the Human Gene Mutation Database (www.hgmd.org). A careful meta-analytical study revealed extensive diversity in terms of the nature of the inserted DNA sequence and has provided new insights into the underlying mutational mechanisms. Some 70% of gross insertions were found to represent sequence duplications of different types (tandem, partial tandem, or complex). Although most of the tandem duplications were explicable by simple replication slippage, the three complex duplications appear to result from multiple slippage events. Some 11% of gross insertions were attributable to nonpolyglutamine repeat expansions (including octapeptide repeat expansions in the prion protein gene [PRNP] and polyalanine tract expansions) and evidence is presented to support the contention that these mutations are also caused by replication slippage rather than by unequal crossing over. Some 17% of gross insertions, all >or=276 bp in length, were found to be due to LINE-1 (L1) retrotransposition involving different types of element (L1 trans-driven Alu, L1 direct, and L1 trans-driven SVA). A second example of pathological mitochondrial-nuclear sequence transfer was identified in the USH1C gene but appears to arise via a novel mechanism, trans-replication slippage. Finally, evidence for another novel mechanism of human genetic disease, involving the possible capture of DNA oligonucleotides, is presented in the context of a 26-bp insertion into the ERCC6 gene.     

Glucose preferences in wild and domestic guinea pigs

Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body $\text{wt.}{}^{\mathrm{<mtext>3</mtext><mtext>4</mtext>}}$ during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.     

尼古丁依赖的功能影像学研究进展

在过去10年中,随着功能脑影像学技术在物质滥用领域的发展,越来越多的研究者运用这些技术以探讨尼古丁成瘾的神经生物学机制。本文主要总结了尼古丁急、慢性暴露下对脑功能影响的神经脑影像学研究进展,证实了尼古丁依赖与中脑边缘犒赏系统、调节注意、记忆、运动以及联想相关脑环路之间的相关性。这些研究发现将为揭示尼古丁依赖的神经生物学机制提供更多的证据支持,进一步促进今后戒烟治疗的发展。