环磷腺苷葡胺治疗慢性充血性心力衰竭的临床疗效观察

目的评价环磷腺苷葡胺治疗慢性充血性心力衰竭的临床疗效。方法2008年8月至2009年2月我院住院病人中选取40例确诊为心力衰竭的患者,随机分为两组各20例。对照组给予常规运用洋地黄,利尿剂,血管紧张素转换酶制剂（ACEI）等药物治疗,治疗组在此基础上加用环磷腺苷葡胺治疗,两周后通过观察临床症状,心功能测值等以判定两组疗效。结果治疗组20例患者中显效5例,有效14例,无效1例,总有效率95.0%;对照组20例患者中显效2例,有效13例,无效5例,总有效率75.0%。两组总有效率比较差异有统计学意义（P〈0.05）。两组治疗后左室射血分数均其治疗前有所改善,差异具有显著性（P〈0.05）;且治疗组治疗后优于对照组,组间相比较,差异有统计学意义（P〈0.05）。结论环磷腺苷葡胺治疗慢性充血性心力衰竭有良好的临床疗效,值得临床推广。     

安徽铜陵药用牡丹不同生长期物质的积累和氮、磷、钾的吸收动态

目的探讨药用牡丹不同生长期氮、磷、钾的吸收规律及其种植的平衡施肥问题。方法采用定期采样,分析不同生长期药用牡丹氮、磷、钾的吸收量及生长量,推算种植过程的科学施肥量。结果药用牡丹地上部快速生长期主要在7月份之前,植株地上部对氮、磷、钾的吸收较高;氮、磷、钾的平均含量1.259%氮、0.114%磷、0.530%钾。从7月开始,地下部明显增重,此时期根部积累的氮、磷、钾较多:根氮、磷、钾的平均含量0.794%氮、0.108%磷、0.380%钾。结论药用牡丹植株生长每年的需氮约1 500 g、需磷160 g、需钾640 g。     

补肾益精方提高卵巢切除大鼠骨质疏松模型松质骨骨质量的实验研究

目的：探讨补肾益精方对去卵巢大鼠骨质疏松模型松质骨骨质量的影响。方法：40只10月龄Wistar雌性大鼠随机分为正常组、模型组、倍美力组和补肾益精方组,每组10只。正常组仅行假手术,其余3组行卵巢切除术。术后第91天开始给药,连续用药90天,处死动物,取出第2腰椎,测定骨质密度和钙、磷、有机质含量;取出第3腰椎,测定其骨质密度和生物力学性能。应用上述多项指标评价骨质量。结果：补肾益精方能明显提高骨质疏松大鼠腰椎骨的骨质密度和钙、磷、有机质含量,增强椎骨的抗压生物力学性能。结论：补肾益精方能够提高去卵巢大鼠松 质骨的骨质量。     

Ac10c: a medium‐ring,cycloaliphatic Cα,α‐disubstituted glycine. Incorporation into model peptides and preferred conformation

Abstract: Two complete series of N‐protected oligopeptide esters to the pentamer level from 1‐amino‐cyclodecane‐1‐carboxylic acid (Ac₁₀c), an α‐amino acid conformationally constrained through a medium‐ring C^α_i ? C^α_i cyclization, and either the l ‐Ala or Aib residue, along with the N‐protected Ac₁₀c monomer and homo‐dimer alkylamides, were synthesized using solution methods and fully characterized. The preferred conformation of these model peptides was assessed in deuterochloroform solution using FT‐IR absorption and ¹H NMR techniques. Furthermore, the molecular structures of two derivatives (Z‐Ac₁₀c‐OH and Fmoc‐Ac₁₀c‐OH) and two peptides (the dipeptide ester Z‐Ac₁₀c‐l ‐Phe‐OMe and the tripeptide ester Z‐Aib‐Ac₁₀c‐Aib‐OtBu) were determined in the crystal state using X‐ray diffraction. The experimental results support the view that β‐bends and 3₁₀‐helices are preferentially adopted by peptides rich in Ac₁₀c, the third largest cycloaliphatic C^α,α‐disubstituted glycine known. This investigation allowed us to complete a detailed conformational analysis of the whole 1‐amino‐cycloalkane‐1‐carboxylic acid (Ac_nc, with n = 3–12) series, which represents the prerequisite for our recent proposal of the ‘Ac_nc scan’ concept.     

异紫堇定的扩血管作用与环核苷酸的关系(英文)

应用血管平滑肌等张收缩和放射免疫测定环核苷酸水平等方法研究了异紫堇定扩血管作用及其机理 .结果表明 ,异紫堇定浓度依赖性地松弛去甲肾上腺素 (NE ,1μmol·L- 1)和KCl(30mmol·L- 1)预收缩的兔胸主动脉螺旋条 ,EC50 分别为 (12 .6± 4 .4 )和 (447± 38) μmol·L- 1,对NE的作用比对KCl强 36倍 .亚甲蓝 (10 μmol·L- 1)可部分抑制异紫堇定的扩血管作用 ,但不受格列本脲 ,吲哚美辛 ,普萘洛尔或N L 硝基精氨酸影响 .异紫堇定还可促进cGMP生成增加 ,并可被亚甲蓝完全阻断 .异紫堇定对cAMP的生成无影响 .结果提示 ,异紫堇定的扩血管作用至少部分通过激活鸟苷酸环化酶 ,促进cGMP的生成实现     

心脏起搏离子通道的分子结构和功能特性(英文)

心脏的起搏受控于一类存在于心脏窦房结被称作If 的离子通道 ,该通道是被细胞膜的超极化所激活 .新近 ,一类被命名为超极化激活及环化核苷酸调控的阳离子 (HCN)通道被克隆 .该家族至少有4个成员 ,即HCN1～HCN4 .其中 2个HCN2和HCN4在心脏有丰富表达 .用异体表达系统表达克隆的HCN2和HCN4通道蛋白 ,其通道特性类似心脏的天然If 通道 .本综述讨论了HCN通道之间的分子结构差异 ,功能性表达特点以及与它们功能特性有关的分子结构     

Pharmaceutical Significance of the Cyclic Imide Form of Recombinant Human Glial Cell Line Derived Neurotrophic Factor

Purpose. The purpose of this paper is to determine the significance of cyclic imide formation of an aspartic acid residue during storage on the pharmaceutical quality of a recombinant human glial cell line-derived neurotrophic factor (rhGDNF) formulation. Methods. A combination of chromatography, peptide mapping, mass spectroscopy, and protein sequencing was used to purify and characterize the degradation product. Circular dichroism, 1,8-ANS and heparin binding, melting temperature determination, bioassays, and preclinical pharmacokinetic and toxicology testing were performed to examine its equivalence to native rhGDNF.Results. The rhGDNF with cyclic imide at aspartic acid residue 96 showed identical activity, structure, pharmacokinetic profile, and toxicity profile to the native rhGDNF. Conclusions. Formation of cyclic imide at aspartic acid residue 96 does not affect the pharmaceutical quality of the rhGDNF formulation.     

Association between Serum Inorganic Phosphorus Levels and Adverse Outcomes in Chronic Kidney Disease: The Fukushima CKD Cohort Study

Objective Although an association between serum inorganic phosphorus levels and a poor prognosis has been noted in dialysis patients, these associations have been insufficiently reported in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients. This study attempted to determine the association between serum inorganic phosphorus levels and adverse outcomes in Japanese NDD-CKD patients. Methods We investigated the relationships between serum inorganic phosphorus levels and adverse outcomes, such as kidney events, cardiovascular events, and all-cause death, in Japanese NDD-CKD patients using longitudinal data from the Fukushima CKD Cohort Study with a median follow-up period of 2.8 years. The study evaluated 822 patients with NDD-CKD enrolled between June 2012 and July 2014. A kidney event was defined as a combination of doubling of the baseline serum creatinine or end-stage renal disease. Cox regression was performed to analyze the relationships of the quartile of the serum inorganic phosphorus with kidney events, cardiovascular events, and all-cause death. Results The frequency of kidney events per 1,000 person-years exhibited a U-shaped distribution based on serum inorganic phosphorus levels, with these levels not significantly associated with an increased risk of cardiovascular events and all-cause death. A multivariable Cox regression analysis showed an increased risk of kidney events for the highest quartile of the serum inorganic phosphorus levels (≥3.7 mg/dL) versus the second quartile (2.9-3.2 mg/dL, hazard ratio, 3.30; 95% confidence interval, 1.50-7.28; p=0.003). There were no significant associations between the serum calcium levels and adverse outcomes. Conclusion Serum inorganic phosphorus levels were associated with an increased risk of CKD progression in Japanese NDD-CKD patients.     

Frequency of serological markers of rheumatoid arthritis in patients with IgA anti‐β2 glycoprotein I antibodies

AimTo determine the frequency of serological markers of RA in patients with anti‐β2 glycoprotein I antibodies (aβ2GPI) of IgA isotype.Material and MethodsA retrospective study was conducted on 67 patients with aβ2GPI‐IgA. Ninety healthy blood donors (HBD) were used as a control group. IgG anti‐cyclic citrullinated peptides antibodies (CCP‐Ab) and rheumatoid factors (RF) IgG, IgA, and IgM were detected by enzyme‐linked immunosorbent assay (ELISA).ResultsSeventeen patients and eight HBD had CCP‐Ab and/or RF (25.4% vs. 8.9%, p = 0.005, CI 95% [14.95; 35.79], odds ratio = 3.5). The frequency of CCP‐Ab was significantly higher in patients than in healthy subjects (14.9% vs. 3.3%, p = 0.009). IgA isotype of RF was significantly higher in patients than in controls (7.5% vs. 0%, p = 0.02). In male patients, CCP‐Ab and/or RF were more frequent than in healthy male subjects (37.5% vs. 11.8%, p = 0.02). In patients, no correlation was found between the levels of aβ2GPI‐IgA and CCP‐Ab (r = 0.082, p = 0.51). There was no correlation between the level aβ2GPI‐IgA and the level of the isotypes of RF (IgG, IgA, and IgM) in patients (r = 0.1, p = 0.37; r = 0.17, p = 0.17 and r = 0.07, p = 0.59 respectively).ConclusionFrequencies of CCP‐Ab and RF are high in patients with aβ2GPI‐IgA suggesting that these patients are susceptible to developing RA.     

Silencing of Nesprin‐2 inhibits the differentiation of myofibroblasts from fibroblasts induced by mechanical stretch

Mechanical force plays a pivotal role in the pathogenesis of hypertrophic scar (HTS). Dermal fibroblasts and myofibroblasts are the key cells involved in HTS. Myofibroblasts in HTS possess different biochemical and biophysical characteristics by which myofibroblasts are often distinguished from fibroblasts. The role of mechanotransducers outside the nucleus in the pathogenesis of HTS has been reported in many studies. However, the role of Nesprin‐2 in HTS is not clear. Hence, we aim to construct a cell model of HTS and explore the role of Nesprin‐2 in this process. Myofibroblasts and fibroblasts were isolated from HTS and healthy skin tissues of the same patient. Fibroblasts were exposed to cyclic stretch with 10% magnitude and a frequency of 0.1 Hz for 3 days, 5 days, and 7 days, respectively. After the cell model was confirmed, fibroblasts transfected with siRNA targeting human Nesprin‐2 were exposed to cyclic stretch. The mechanical behaviour and biochemical reaction of the dermal fibroblasts were analysed. The stretched fibroblasts at day 5 showed the same mechanotransductive and biochemical features as unstretched myofibroblasts. Mechanical strain could induce the myofibroblasts differentiation and a cell model of HTS was established successfully at day 5. The expressions of lamin A/C, alpha‐smooth muscle actin, transforming growth factor beta 1, and collagen type I in fibroblasts were reduced by the silencing of Nesprin‐2. Mechanical strain could induce the myofibroblasts differentiation and silencing of Nesprin‐2 could block the mechanical stimulation of terminal myofibroblasts differentiation. Nesprin‐2 might be a potential target to treat the HTS.