人单核巨噬细胞泡沫化抑制剂筛选模型的建立及应用

目的: 建立人单核巨噬细胞泡沫化抑制剂筛选模型,筛选得到可抑制细胞泡沫化的抑制剂.方法: U937单核细胞经100 nmol·L-1佛波酯(PMA)诱导72 h分化为巨噬细胞后,换无血清培养液于96孔板中,每毫升含巨噬细胞1×106个,每孔再加入80 mg·L-1氧化的低密度脂蛋白(ox-LDL),37 ℃培养48 h,建立单核巨噬细胞泡沫化模型.利用微生物发酵液,或单一的化合物样品与其共孵育,油红.染色后观察细胞胞内变化,寻找对泡沫细胞形成有抑制作用的样品.利用基因工程技术表达的人清道夫受体A类II型的胞外部分,在本模型中可抑制巨噬细胞泡沫化的形成,进一步验证了模型的可行性.结果: 从2000 个微生物发酵液中筛选到6株微生物发酵液为阳性,从10个化合物中发现一个有抑制巨噬细胞泡沫化活性的新化合物.结论: 本模型可用于细胞泡沫化抑制剂的高通量筛选.     

3-苯基乳酸的研究进展

介绍了3-苯基乳酸的结构、制备、手性拆分等的研究现状，并阐述了其抑菌、药理作用及在医药、化工等领域的应用。     

许树化学成分研究

目的研究许树Clerodendrum inerme的化学成分。方法利用硅胶柱色谱进行分离和纯化,通过光谱分析鉴定结构。结果分离到8个化合物,鉴定为木栓酮(friedelin,Ⅰ)、豆甾醇(stigmasterol,Ⅱ)、白桦酸(betulinicacid,Ⅲ)、金合欢素(acacetin,Ⅲ)、丁香酸(syringicacid,Ⅳ)、对甲氧基苯甲酸(Ⅴ)、芹菜素(apigenin,Ⅵ)和胡萝卜苷(daucosterol,Ⅶ)。结论化合物Ⅱ、Ⅲ、Ⅳ、Ⅳ、Ⅶ为首次从该植物中分离得到。     

Stretch of mammalian nerve in vitro: effect on compound action potentials

Stretch of nerve has been reported to decrease the amplitude of the compound action potential (CAP) with a complete block appearing in approximately 30 minutes. But for the most part, those experiments were carried out in vivo, and it is generally accepted that the failure of responses was due to a closure of vessels supplying the nerve with a resulting ischemia and anoxia. These studies were undertaken to determine if stretch of nerve has effects that are independent of interference with its vascular supply. In the studies, lengths of rat sciatic and dog peroneal nerves were removed and placed in a chamber supplied with oxygen in which their CAPs were continuously elicited and recorded. This in vitro preparation obviated interference with the nerve's metabolism on stretching. We have previously shown that the form change termed 'beading,' appearing within 10 seconds and reversing as quickly on relaxation, can be elicited with tensions of only several grams. We wished to determine if stretch adequate to produce beading could alter CAPs with the same rapidity. Tensions below 2 g had little effect. On applying tensions of 10-100 g, levels well above those needed to bead the fibers, both increases and decreases of CAP amplitude were seen. The changes occurred within 10 seconds of stretch application, the time at which beading arises with stretch. Although the decreases of CAP amplitudes could be accounted for by beading, the degree of CAP change did not correspond to the amount of tension applied. We hypothesize that the constrictions in the beaded fibers increase axial resistivity and diminish local currents so as to block conduction. The lack of an increasing degree of decreased CAP amplitude with increases in tension is ascribed to the inhibition of elongation offered by the collagen fibrils present in nerve. Collagenase applied to nerves allowed a further increase in length, producing a 'hyperbeading,' showing much longer lengths of beading constrictions on stretch. This would further increase axial resistance and is taken to account for the greater decreases of CAP amplitudes seen following collagenase treatment. To account for those cases where increases of CAP amplitude were seen on stretch, we hypothesize that stretch can also cause an increase in the excitability of the nodes. The outcome of stretch in any given nerve would be the resultant of two opposing actions; beading of the internodes causes a decrease of local currents leading to block of CAPs, while an increased excitability of the nodes acts to augment the responses.     

蔡炳勤教授治疗外科术后疑难发热医案三则

蔡炳勤教授为广东省名中医,全国老中医药专家学术经验继承工作指导老师,从事中医外科医、教、研40余年,学验俱丰,在中医外科方面颇有建树,提出许多独到的见解,尤其是疑难杂症的治疗,蔡老认为“善治常者,亦善治其变”。笔者有幸侍诊于侧,聆听教诲,受益匪浅,凡遇临床验案便悉心整理。以     

牛磺酸治疗高血压病的疗效及对血管内皮细胞功能的影响

目的观察牛磺酸对原发性高血压病(EH)病人的疗效及血管内皮活性物质内皮素1(ET-1)、血栓素A2(TXA2)、一氧化氮(NO)和降钙素基因相关肽(CGRP)的影响。方法56例EH病人用牛磺酸治疗2个月,观察用药前后血中ET-1、NO、CGRP和TXA2的变化。结果牛磺酸治疗EH总有效率为71.4%。牛磺酸治疗后血中NO、CGRP浓度均较治疗前显著升高(P<0.01),血中ET、TXA2浓度显著下降(P<0.01)。结论牛磺酸有较好的降压作用,可明显改善EH病人血管内皮功能。     

The attenuation effect of potassium 2‐(1‐hydroxypentyl)‐benzoate in a mouse model of diabetes‐associated cognitive decline: The protein expression in the brain

Aims dl‐PHPB (potassium 2‐(1‐hydroxypentyl)‐benzoate) has been shown to have neuroprotective effects against acute cerebral ischemia, vascular dementia, and Alzheimer''s disease. The aim of this study was to investigate the effects of dl‐PHPB on memory deficits and preliminarily explore the underlying molecular mechanism.MethodsBlood glucose and behavioral performance were evaluated in the KK‐A^y diabetic mouse model before and after dl‐PHPB administration. Two‐dimensional difference gel electrophoresis (2D‐DIGE)‐based proteomics was used to identify differentially expressed proteins in brain tissue. Western blotting was used to study the molecular mechanism of the related signaling pathways.ResultsThree‐month‐old KK‐A^y mice were given 150 mg/kg dl‐PHPB by oral gavage for 2 months, which produced no effect on the level of serum glucose. In the Morris water maze test, KK‐A^y mice treated with dl‐PHPB showed significant improvements in spatial learning and memory deficits compared with vehicle‐treated KK‐A^y mice. Additionally, we performed 2D‐DIGE to compare brain proteomes of 5‐month KK‐A^y mice treated with and without dl‐PHPB. We found 14 altered proteins in the cortex and 11 in the hippocampus; two of the 25 altered proteins and another four proteins that were identified in a previous study on KK‐A^y mice were then validated by western blot to further confirm whether dl‐PHPB can reverse the expression levels of these proteins. The phosphoinositide 3‐kinase/protein kinase B/glycogen synthase kinase‐3β (PI3K/Akt/GSK‐3β) signaling pathway was also changed in KK‐A^y mice and dl‐PHPB treatment could reverse it.ConclusionsThese results indicate that dl‐PHPB may play a potential role in diabetes‐associated cognitive impairment through PI3K/Akt/GSK‐3β signaling pathway and the differentially expressed proteins may become putative therapeutic targets.     

Use of the optimized sodium thiosulfate regimen for the treatment of calciphylaxis in Chinese patients

BackgroundSodium thiosulfate (STS) can be used to treat patients diagnosed with calciphylaxis, which is a rare life-threatening syndrome. However, our patients treated with the recommended STS regimen presented with serious adverse events, resulting in treatment withdrawal. Then an optimized STS regimen was used to increase the tolerance of patients to STS and improve treatment continuation. The curative effect of the new regimen is not yet definite. Therefore, this study aimed to evaluate the response to the use of the optimized STS regimen for the treatment of calciphylaxis in Chinese patients during the first three courses of treatment.MethodsDemographic, clinical, and laboratory data were retrospectively collected on 31 calciphylaxis patients with chronic kidney disease (CKD) or end-stage kidney disease (ESKD) treated with the optimized STS regimen. The primary outcome was a clinical improvement. The secondary outcomes included survival rate and adverse events.ResultsTwenty-five patients (over 80%) achieved clinical improvement considering improvement or nonspecific changes of skin lesions (80.65%) and pain relief (100%). Furthermore, 54.84% of patients did not experience any adverse events and none died from complications. During a median follow-up of 9 months (interquartile range 4‒19), 27 patients (87.10%) survived; additionally, 13 patients (41.94%) survived after a one-year follow-up period.ConclusionThe optimized STS regimen is relatively safe, associated with satisfactory outcomes, and well tolerated by patients for short to medium treatment duration. Hence, it is a promising approach for the treatment of patients diagnosed with calciphylaxis.     

糖尿病大鼠早期视网膜神经节细胞凋亡机制的探讨

目的：探讨糖尿病大鼠模型早期视网膜神经节细胞(retinal ganglion cells,RGCs)凋亡的机制。

方法：SD大鼠60只,随机分为对照组(CON)及糖尿病组(DM),糖尿病组一次性腹腔注射1% STZ诱发糖尿病鼠模型,两组于第4,8,12wk分别行HE、透射电镜及TUNEL法检测RGCs的凋亡情况,并应用激光共聚焦显微镜检测RGCs内钙离子浓度的变化。

结果：糖尿病组第8wk开始出现RGCs数量减少、细胞排列紊乱的病理改变,第12wk更为明显。糖尿病组透射电镜下可见第4wk时RGCs出现线粒体肿胀; 第8wk时RGCs内肿胀的线粒体更为明显、数目增多,染色质边集于核膜周边,部分细胞体积缩小、细胞器减少; 第12wk时出现RGCs体积变小,甚至出现细胞核断裂。TUNEL阳性RGCs最早于糖尿病组第4wk时出现,随病程延长凋亡的阳性细胞逐渐增多,凋亡指数与同期对照组相比,差异有统计学意义(P<0.01)。糖尿病组第8,12wk时RGCs内钙离子浓度明显高于同期对照组,差异显著(P<0.01); 糖尿病组第8wk与第12wk比较,升高差异亦有统计学意义(P<0.05)。

结论：糖尿病早期出现了视网膜神经节细胞的凋亡,其机制可能与细胞内钙离子浓度升高有关。