The fertilizing ability of human epididymal sperm

Purpose: Membrane cofactor protein (MCP), CD46, whose primary function is to protect host cells from homologous complement, has been presumed to serve as a sperm adhesion molecule for oocytes. The purpose of this study was to clarify the relationship between the properties of MCP expressed on epididymal sperm and their fertilizing ability in a recently developed strategy for assisted reproduction. Methods: We collected ejaculated sperm from normal subjects and epididymal sperm from vasectomized subjects and patients with congenital absence of the vas deferens. Western blotting and cofactor activity assay were performed to investigated the structural and functional properties of MCP. Results: Epididymal spermatozoa which showed a reduced fertilizing ability tended to react poorly with antibodies against MCP and also showed low cofactor activity, indicating weak complement regulatory activity compared to that of ejaculated spermatozoa. Conclusions: MCP is sufficiently expressed in ejaculated sperm in men with a normally developed epididymis but is diminished in epididymal sperm from men with congenital or acquired obstruction of the vas deferens.     

中医研究的三个重要趋势

就科学理念对实验设计的指导作用而言，当前中医研究有三个重要趋势：1．从线性的简单系统走向开放的复杂巨系统；2．由模式生物走向人体实验；3．由“纯粹”科学走向与人文科学相融合。     

中国科技期刊如何进入国际信息检索系统

以被多种国际著名信息检索系统收录的World Journal of Gastroenterology（WJG）杂志的发展历程为样例。探讨如何提高中国出版的科技期刊被国际信息系统收录的命中率，提高期刊的国际地位和知名度，更好地促进与国际的学术交流。     

FDA relations during drug development

Working closely and cooperatively with regulatory authorities during drug development is vital to successful drug development programs. In the United States, the drug development team includes not only members of the key disciplines of drug discovery, clinical research, regulatory affairs, marketing, chemistry, toxicology, and legal aspects, but also the Food and Drug Administration (FDA). New regulations encourage meetings at the pre-investigational new drug (pre-IND), end-of-phase-2, and pre-new drug application (pre-NDA) submission phases. Appropriate informal discussions via fax and telephone are also encouraged. By proactively interacting with the FDA, the pharmaceutical industry increases the probability of a successful drug development program.     

管理学课程教学创新探讨

管理学是研究管理活动的科学知识体系，是一门综合性应用学科，具有科学性和艺术性。针对管理学在新形势下不断呈现出的特点，探讨了管理学课程的教学目标、教学内容及教学方法应该作出的调整和创新。     

干扰素调节因子 5、粒细胞 -巨噬细胞集落刺激因子在细菌性肺炎病儿血清中的表达及预后价值

目的探讨干扰素调节因子 5(interferon regulatory factor 5,IRF5)、粒细胞 -巨噬细胞集落刺激因子( granulocyte-macrophage colony-stimulating factor,GM-CSF)在细菌性肺炎病儿血清中的表达变化及疾病预后价值。方法选取 2019年 4月至 2021年 5月中国人民解放军联勤保障部队第九二八医院收治的细菌感染性肺炎病儿 96例作为细菌组,同期非细菌感染性肺炎病儿 88例作为非细菌组,另外选取健康体检儿童 96例为对照组,收集检测三组病儿基本临床资料。检测血清中 IRF5、GM-CSF及其组间差异;采用 Pearson法分析细菌性肺炎病儿血清 IRF5、GM-CSF水平与病情指标的相关性;应用受试者操作特征曲线(ROC曲线)分析 IRF5、GM-CSF及二者联合预测细菌性肺炎预后的价值。结果细菌组血清 IRF5水平［(38.85±13.86)ng/L］显著高于非细菌组［( 11.15±4.37)ng/L］和对照组［( 10.76±1.55)ng/L］,且重症组高于轻症组( P<0.05);细菌组血清 GM-CSF水平［(54.73±16.56)ng/L］显著低于非细菌组［(246.73±28.94)ng/L］和对照组［(250.64±55.67)ng/L］,且重症组低于轻症组( P<0.05)。重症组气促、吐沫、三凹征、肺部明显湿啰音比例、 C反应蛋白( C-reactive protein,CRP)、白细胞水平显著高于轻症组、非细菌组(P<0.05)轻症组、非细菌组 CRP水平显著高于对照组( P<0.05),非细菌组 CRP水平显著高于对照组( P<0.05)。血清 IRF5水平与 CRP、,白细胞、临床肺部感染评分( clinical pulmonary infection score,CPIS)均呈正相关( r=0.34、0.36、0.41,P<0.05)血清 GM-CSF水平与 CRP、白细胞、 CPIS均呈负相关( r=-0.40、-0.32、-0.45,P<0.05)。预后不良组血清 IRF5水平高于预后良好,组,血清 GM-CSF水平低于预后良好组( P<0.05)。 ROC曲线显示, IRF5、GM-CSF对预后预测的 AUC分别为 0.90、0.87,二者联合对预后预测的 AUC为 0.96,明显高于二者单独诊断,(Z联合 vs.IRF5=2.86,P=0.004;Z联合 vs.GM-CSF =2.24,P=0.025),其灵敏度、特异度分别为 90.32%、90.77%。结论细菌性肺炎病儿血清 IRF5水平升高, GM-CSF水平降低,二者在评估病情进展及疾病预后预测方面具有较高的价值。     

Recommendations for Better Civic Learning: Building and Rebuilding Democracy

This is the concluding essay for a special report from The Hastings Center entitled Democracy in Crisis: Civic Learning and the Reconstruction of Common Purpose, which grew out of a project supported by the John S. and James L. Knight Foundation. This essay provides an integrative discussion of various theoretical and practical reform perspectives offered by other essays in the report. It also offers a number of recommendations. It notes that the aim of the special report is not to propose specific reform measures but, rather, to consider larger, more theoretic concerns related to political and economic questions, which are personal and structural—psychological, cultural, and institutional—at the same time. In response, this essay argues that the best relationship between the citizenry and government in a democracy is not one of deference, nor one of contestation, but one that is critically constructive, which in turn is linked to practices of civic learning. To be constructive, citizens need scientific literacy, an understanding of how government and other institutions work, critical thinking abilities, and many open and diverse forums for civic learning to offset the increasingly isolating media “bubbles” that are the only source of information for many. The essay then formulates five recommendations designed to facilitate critically constructive citizenship and civic learning. These are creating a basis for civic participation, acquiring information, talking to each other, designing institutional change, and achieving deliberation.     

中医专业七年制学生临床科研能力培养的实践与思考

在中医专业七年制学生的临床教学中,坚持并深化教育教学改革,通过规范毕业论文管理、定期举办"研究生论坛"、设立"萌芽计划"科研基金、开设专题学术讲座、培养学生科技创新意识等措施,致力于培养学生的临床科研能力,取得了显著成效。     

Functional and molecular characterization of multiple K-Cl cotransporter isoforms in corneal epithelial cells

The dependence of regulatory volume decrease (RVD) activity on potassium-chloride cotransporter (KCC) isoform expression was characterized in corneal epithelial cells (CEC). During exposure to a 50% hypotonic challenge, the RVD response was larger in SV40-immortalized human CEC (HCEC) than in SV40-immortalized rabbit CEC (RCEC). A KCC inhibitor-[(dihydroindenyl)oxy] alkanoic acid (DIOA)-blocked RVD more in HCEC than RCEC. Under isotonic conditions, N-ethylmaleimide (NEM) produced KCC activation and transient cell shrinkage. Both of these changes were greater in HCEC than in RCEC. Immunoblot analysis of HCEC, RCEC, primary human CEC (pHCEC), and primary bovine CEC (BCEC) plasma membrane enriched fractions revealed KCC1, KCC3, and KCC4 isoform expression, whereas KCC2 was undetectable. During a hypotonic challenge, KCC1 membrane content increased more rapidly in HCEC than in RCEC. Such a challenge induced a larger increase and more transient p44/42MAPK activation in HCEC than RCEC. On the other hand, HCEC and RCEC p38MAPK phosphorylation reached peak activations at 2.5 and 15 min, respectively. Only in HCEC, pharmacological manipulation of KCC activity modified the hypotonicity-induced activation of p44/42MAPK, whereas p38MAPK phosphorylation was insensitive to such procedures in both cell lines. Larger increases in HCEC KCC1 membrane protein content correlated with their ability to undergo faster and more complete RVD. Furthermore, pharmacological activation of KCC increased p44/42MAPK phosphorylation in HCEC but not in RCEC, presumably a reflection of low KCC1 membrane expression in RCEC. These findings suggest that KCC1 plays a role in (i) maintaining isotonic steady-state cell volume homeostasis, (ii) recovery of isotonic cell volume after a hypotonic challenge through RVD, and (iii) regulating hypotonicity-induced activation of the p44/42MAPK signaling pathway required for cell proliferation.