重组人干扰素a1b注射液与利巴韦林治疗手足口病疗效和安全性的系统评价

目的:评价重组人干扰素 a1b 注射液和利巴韦林治疗手足口病的有效性和安全性。 方法:通过 PubMed、Cochrane 图书馆、中国知网、万方数据库及中国生物医学文献数据库检索重组人干扰素 a1b 注射液治疗手足口病的随机对照研究文献,提取文献信息并进行方法学质量评价,应用 RevMan 5.3 软件进行 Meta 分析。 结果:最终纳入 14 篇研究,干扰素组 913 例,利巴韦林组 901 例,共计 1 814 例患儿。 干扰素组治疗总有效率、退热时间、皮疹消退时间和疱疹溃疡愈合时间均优于利巴韦林组,差异具有统计学意义[OR=6.86,95%CI(4.97,9.46);MD=-1.55,95% CI(-2.13,-0.96);MD= -1.71,95% CI(-2.31,-1.11);MD=-1.13,95%CI(-1.38,-0.88),P<0.05]。 干扰素组不良反应发生率低于利巴韦林组。 结论:重组人干扰素 a1b 注射液联合常规治疗用于小儿手足口病较利巴韦林联合常规治疗有更好的疗效及安全性,但限于纳入研究质量总体不高,需更多高质量、多中心临床研究进一步验证。     

Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in mice

Aim:

Aliskiren (ALK) is a renin inhibitor that has been used in the treatment of hypertension. The aim of this study was to determine whether ALK could ameliorate pressure overload-induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.

Methods:

Transverse aortic constriction (TAC) was performed in mice to induce heart pressure overload. ALK (150 mg·kg⁻¹·d⁻¹, po), the autophagy inhibitor 3-methyladenine (10 mg·kg⁻¹ per week, ip) or the PKCβI inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY333531","term_id":"1257370768","term_text":"LY333531"}}LY333531 (1 mg·kg⁻¹·d-¹, po) was administered to the mice for 4 weeks. Heart hypertrophy, fibrosis and function were evaluated based on echocardiography, histological and biochemical measurements. Mechanically stretched cardiomyocytes of rats were used for in vitro experiments. The levels of signaling proteins were measured using Western blotting, while the expression of the relevant genes was analyzed using real-time QRT-PCR.

Results:

TAC induced marked heart hypertrophy and fibrosis, accompanied by high levels of Ang II in plasma and heart, and by PKCβI/α and ERK1/2 phosphorylation in heart. Meanwhile, TAC induced autophagic responses in heart, i.e. increases in autophagic structures, expression of Atg5 and Atg16 L1 mRNAs and LC3-II and Beclin-1 proteins. These pathological alterations in TAC-mice were significantly ameliorated or blocked by ALK administration. In TAC-mice, 3-methyladenine administration also ameliorated heart hypertrophy, fibrosis and dysfunction, while {"type":"entrez-nucleotide","attrs":{"text":"LY333531","term_id":"1257370768","term_text":"LY333531"}}LY333531 administration inhibited ERK phosphorylation and autophagy in heart. In mechanically stretched cardiomyocytes, {"type":"entrez-protein","attrs":{"text":"CGP53353","term_id":"875191971","term_text":"CGP53353"}}CGP53353 (a PKCβI inhibitor) prevented ERK phosphorylation and autophagic responses, while U0126 (an ERK inhibitor) blocked autophagic responses.

Conclusion:

ALK ameliorates heart hypertrophy, fibrosis and dysfunction in the mouse model in setting of chronic pressure overload, via suppressing Ang II-PKCβI-ERK1/2-regulated autophagy.     

黄连解毒汤配方颗粒中4种成分含量的测定及与传统汤剂的比较

目的：建立一种同时测定黄连解毒汤配方颗粒中4种成分（栀子苷、黄芩苷、盐酸巴马汀、盐酸小檗碱）含量的HPLC方法,对黄连解毒汤配方颗粒和传统汤剂的主要色谱峰及成分含量进行比较。方法：采用菲罗门Gemini 5u C18110A色谱柱（250mm×4.6mm,5μm）,以乙腈为流动相A,以每100mL水中含1mL pH=6.0的醋酸-醋酸铵缓冲溶液为流动相B;梯度洗脱,体积流量为1.0mL/min,检测波长260nm,柱温30℃。结果：在39min内黄连解毒汤配方颗粒中栀子苷、黄芩苷、盐酸巴马汀、盐酸小檗碱4种成分完全分离;回归方程显示4种成分的峰面积与其浓度呈良好的线性关系;4种成分的平均加样回收率（n=6）为95.02%～104.57%, RSD均小于3.0%;黄连解毒汤配方颗粒与传统汤剂的主要色谱峰的峰形峰位一致,成分含量相当。结论：该方法简单快捷,灵敏度高,稳定、重复性好,可用于黄连解毒汤配方颗粒的质量控制,黄连解毒汤配方颗粒与传统汤剂的主要成分一致,可为其替代传统汤剂作为理论依据。     

Cytotoxic and anti-inflammatory constituents from the seeds of Descurainia sophia

A new sinapoyl glycoside, 1,3-di-O-sinapoyl-β-d-glucopyranose (1) along with 13 known compounds, including, sinapoyl glycosides (2 and 3), cardenolide glycoside (4), flavonoids (5–10), lignan (11), phenolic acids (12 and 13), and phytosterol (14), were isolated from the seeds of Descurainia sophia by chromatographic separation methods. The structures of 1–14 were determined by the interpretation of spectroscopic data as well as by comparison of that data with previously reported values. Compounds 2, 3, 5, 6, and 11 were identified in and isolated from this plant for the first time in this study. All isolates were evaluated for in vitro cytotoxic activities against seven human cancer cell lines and for in vitro anti-inflammatory potential using LPS-stimulated RAW264.7 murine macrophages. Compound 4 showed potent cytotoxicity (IC₅₀ values ranging from 0.034 to 0.596 μM) against all human cancer cell lines tested and was identified as the main active cytotoxic constituent of this plant. Compound 8 (ED₅₀ = 5.45 μM) and 11 (ED₅₀ = 10.02 μM) exerted dose-dependent inhibitory effects on NO production in LPS-stimulated RAW264.7 cells.     

慢性根尖周炎一次性根管治疗的疗效分析

目的 观察分析慢性根尖周炎一次性根管治疗的长期疗效,评价慢性根尖周炎一次性根管治疗的临床可行性.方法 选取临床诊断为慢性根尖周炎的磨牙228颗为研究对象.120颗患牙在一次治疗内完成去除腐质、清理髓腔、根管预备和根管充填,设为Ⅰ组;108颗患牙经3次治疗后完成根管充填（第一次去除腐质,髓腔清理后封CP一周,第二次根管预备后封氢氧化钙1周,第三次完成根管充填）,设为Ⅱ组.两组均采用冠向下技术预备根管,3％的次氯酸钠和17％的EDTA冲洗根管,侧向加压法充填根管.术后2年随访,比较两组的临床疗效.结果 Ⅰ组根管治疗的成功率88.79％ （95/120）;Ⅱ组根管治疗的成功率92.08％（93/108）.x 2检验结果显示两组疗效差异没有统计学意义（x 2=0.649,P＞0.05）.结论 慢性根尖周炎根管治疗采用一次法或多次法完成,其长期疗效并无区别.     

新生儿早发型B族链球菌败血症16例临床分析

目的：探讨早发型新生儿B族链球菌（GBS）败血症的临床特征及治疗方法。方法：回顾性分析2011年1月至2013年10月我院新生儿科收治的16例新生儿早发性GBS败血症病例,分析临床特点、治疗方法和预后。结果：16例早发型GBS败血症中足月儿8例,早产儿8例;1 h内起病9例,均表现为呼吸困难,临床合并肺炎,有发生持续肺动脉高压可能;1~3 d起病7例,临床表现以败血症或化脓性脑膜炎为主;并发肺炎12例、休克5例、化脓性脑膜炎3例（均为足月儿）。药敏试验显示GBS对青霉素、氨苄西林、头孢曲松、万古霉素等敏感。死亡3例,均为超低出生体质量儿（生后72 h内死亡）;脑积水1例,腹腔引流术后,确诊脑瘫;1例脑室扩大。结论：早发型GBS败血症早期起病以呼吸道表现为主,1~3 d起病以败血症及颅内感染为主要表现,有导致神经系统后遗症及死亡可能。     

Fc融合蛋白在药学领域的研究进展

Fc融合蛋白是指利用基因工程等技术将某种具有生物活性的功能蛋白分子与Fc片段融合而产生的新型重组蛋白,其不仅保留了功能蛋白分子的生物学活性,还具有一些抗体的性质,如通过结合相关Fc受体延长半衰期和引发抗体依赖细胞介导的细胞毒性效应等。对Fc融合蛋白及其在药学领域的研究进展进行了综述。     

治疗自身免疫性疾病的抗细胞因子疫苗

抗细胞因子疫苗是针对疾病相关细胞因子而设计与构建的一类能激发体液免疫应答的主动免疫治疗性疫苗,是用于自身免疫性疾病的一种极具潜力的新型疗法。目前研究与开发的抗细胞因子疫苗主要有2种类型,一种是通过偶联载体或直接修饰为细胞因子引入外源表位而构建的蛋白疫苗,另一种则是可表达细胞因子免疫原的核酸疫苗。这两类疫苗在临床前及临床研究中,对各种自身免疫性疾病均显现出治疗活性。简介各类抗细胞因子疫苗及其作用机制,综述用于治疗类风湿性关节炎、多发性硬化症、系统性红斑狼疮等各种自身免疫性疾病的抗细胞因子疫苗研究进展。     

基于蒙特卡洛模拟评价头孢噻肟/他唑巴坦对产ESBL肠杆科细菌不同给药方案研究

目的:探讨头孢噻肟/他唑巴坦对产超广谱β-内酰胺酶(ESBL)大肠埃希菌和肺炎克雷伯菌临床分离株的最低抑菌浓度(MIC)分布情况,评估头孢噻肟/他唑巴坦不同给药方案下％fT＞MIC≥50％达标率,为该药临床给药方案的筛选及优化提供参考.方法:采用微量肉汤稀释法测定头孢噻肟单药、头孢噻肟/他唑巴坦(他唑巴坦固定质量浓度4...     

双黄连冻干粉通过抑制MEK-ERK信号通路诱导急性淋巴细胞白血病Nalm6细胞凋亡

目的探讨双黄连(SHL)冻干粉诱导急性B淋巴细胞白血病细胞(Nalm6)凋亡的机制。方法采用0、0.025、0.05、0.1、0.2、0.4、0.8 g/L的SHL处理急性白血病细胞株(Nalm6、Jurkat、Molt4、KG1a),CCK-8法检测细胞增殖抑制率,并计算半数抑制浓度(IC50)。Nalm6细胞分为空白对照组(含有10%胎牛血清的RPMI 1640培养基)和SHL0.1、0.2、0.4 g/L组。流式细胞术检测各组细胞周期分布及凋亡情况,Hoechst 33342染色细胞后观察细胞凋亡形态学改变。蛋白免疫印迹法检测各组Nalm6细胞MEK-ERK-c-Myc信号通路蛋白以及凋亡相关蛋白的表达情况。结果SHL对Nalm6的IC50最低,为(0.11±0.01)g/L。细胞周期分析显示,0.1～0.4 g/L SHL处理后,Nalm6的细胞周期分布无明显变化,但随着处理浓度的升高,Nalm6凋亡细胞数增多,总凋亡率升高,t Bid、cleaved Caspase-9、cleavedCaspase-3、cleaved PARP表达升高,MEK/ERK通路相关蛋白p-MEK/...