Optimized prodrug approach: A means for achieving enhanced anti-inflammatory potential in experimentally induced colitis

In the present study, prodrug of ketoprofen was synthesized and evaluated in vitro to optimize the prodrug, and in vivo to observe the reduction in gastrointestinal disturbance and enhanced colonic anti- inflammatory potential for the prodrug. The prodrug was synthesized by coupling ketoprofen with l-glycine (KET-GLY). In vitro reversion of KET-GLY to ketoprofen was carried out in different pHs and in pH 6.8 containing optimized rat fecal material. In vivo healing potential of KET-GLY was evaluated in acetic acid-induced experimental colitis model. In vitro reversion studies suggested that KET-GLY remained intact in stomach but released the free drug at pH 6.8 containing fresh rat fecal material, where the colonic microfloral enzymes (amidase) hydrolyzed the KET-GLY amide linkage, releasing the free drug. In vivo evaluation indicated KET-GLY to be less toxic in stomach, with enhanced anti-inflammatory potential in the colonic region. These findings suggested KET-GLY to be better in action compared with the parent drug.     

环形电切锥切术治疗老年宫颈高度病变病人的临床疗效

目的探讨环形电切锥切术(LEEP)治疗老年宫颈高度病变病人的临床效果及对逆转率的影响。方法选择2017年6月至2019年6月老年宫颈高度病变病人143例作为对象,采用随机数表法分为对照组(n=70)和观察组(n=73)。对照组采用宫颈冷刀锥切术治疗,观察组采用LEEP治疗,术后3 d对病人手术指标进行评估,术后对病人进行6个月随访,比较2组手术指标、逆转率、并发症发生率及术后生活质量。结果观察组手术、住院及切口愈合的时间,术中出血量及手术费用均少于对照组(P<0.05)。术后6个月,2组宫颈管粘连、感染、阴道出血的发生率差异均无统计学意义(P>0.05)。2组术后1、6个月逆转率差异均无统计学意义(P>0.05)。观察组术后6个月的健康、食欲、精神症状、躯体感觉及睡眠状态评分均高于对照组(P<0.05)。结论LEEP用于老年宫颈高度病变病人中,手术创伤较小,能提高逆转率,降低术后并发症发生率,有助于提高病人生活质量,值得推广应用。     

Risk Factors for Mild Cognitive Impairment,Dementia and Mortality: The Sydney Memory and Ageing Study

Background

The nature and commonality of late-life risk factors for mild cognitive impairment (MCI), dementia, and mortality remain unclear. Our aim was to investigate potential risk factors, simultaneously in a single cohort including many individuals initially with normal cognition and followed for 6 years.

有机磷农药分子片段诱发沙门氏菌回复突变的计算机辅助评价

用计算机辅助分子片段评价程序分析了５９种有机磷化合物诱发沙门氏菌回复突变的资料。发现：有机磷诱发沙门氏菌回变与带甲基的分子片段有关，而带乙基分子片段的有机磷的阳性概率极低；磷酰基上的氧原子似有增强诱变性的作用，硫代磷酰基上的硫原子则似有减弱作用。提示：在这些相关片段中，甲氧磷酰基片段与有机磷诱发沙门氏菌回变相关，可推荐为有机磷诱发阳性的特征描述符；而乙基硫羰磷酰基阳性的概率极低，为阴性结果的描述符。     

SiRNA逆转人红白血病细胞株(K562/ADM)阿霉素耐药性的实验研究

目的:研究小分子干扰RNA片段(small inteffering RNA,siRNA)对人红白血病细胞株K562/ADM细胞mdr1基因表达及药物敏感性的影响,探索新的耐药逆转途径.方法:siRNA根椐GeneBank已知序列设计,在脂质体介导下转染K562/ADM细胞;用流式细胞仪检测K562/ADM细胞Pgp的表达;用MTT检测其对阿霉素ADM的敏感性;用PCR-ELISA法检测K562/ADM细胞的端粒酶活性.结果:siRNA转染后K562/ADM细胞Pgp的表达明显下降,对阿霉素ADM的IC50从8.7μg/ml降到5 μg/ml,端粒酶活性明显下调.结论:siRNA有效逆转了mdr1介导的耐药性,不失为一种新型、有效的肿瘤耐药逆转途径.     

丹芪葛酮逆转心肌肥厚的实验研究

目的观察丹芪葛酮对自发性高血压大鼠信号传导途径的影响，并探讨其逆转心肌肥厚作用机制。方法自发性高血压大鼠（SHR）24只，随机分为生理盐水组（ND）；卡托普利组（CAP）、丹芪葛酮组（DGH），每组各8只，另设立正常的Wister大鼠为对照组（CG）。于连续用药8周后取材，测定全心质量／体质量、左室质量／体质量比值，心室肌组织中Gaq／11，plc-β3蛋白及IP3、心肌血管紧张素Ⅱ（AngⅡ）和内皮素（ET）含量。结果丹芪葛酮组左心指数及左心室AngⅡ、ET表达与ND组比较均下降（P均〈0．05）。左心室肥厚时，Gaq／11蛋白表达无显著性差异，plc-β3蛋白浓度高于CG组（P〈0．05），IP3浓度明显高于CG组（P〈0．01）；CAP和DGH组与ND组比较P〈0．05，但CAP组与DGH组间无显著性差异。结论丹芪葛酮组方通过对心肌信号传导的影响而达到逆转心肌肥厚的作用。     

淫羊藿甙抗癌作用机制的实验研究

中药单体淫羊藿百一种新型的生物反应调节剂和诱导分化剂。为进一步探讨淫羊藿 作用机制,我们将淫羊藿和于人高转移肺癌细胞ＰＧ,采用ＭＴＴ、放免、流式细胞术、粘附实验,运动侵袭实验等多种手段进行了检测。结果表明,淫羊藿夼直接抑癌作用较强,但却能影响ＰＧ细胞周期的时相分布,使Ｓ期减小,并能升高细胞内ｃ－ＡＭＰ水平,降低ｃＧＭＰ水平,提示ｃＡＭＰ／ｃＧＭＰ比值,同时降低ＰＧ细胞对胞外基质的粘附性及侵袭、运动     

微RNA-103a-3p靶向调节Kazal基序富含半胱氨酸的逆转诱导蛋白表达对胃癌细胞迁移和侵袭能力的影响

目的 探讨胃癌细胞中微RNA(miR)-103a-3p与Kazal基序富含半胱氨酸的逆转诱导蛋白(RECK)表达的关系及其对胃癌细胞迁移、侵袭能力的影响。方法 将对数生长期人胃癌细胞系MKN-45细胞随机分为阴性对照(NC)组、miR-103a-3p组、RECK组、miR-103a-3p+RECK组。NC组细胞共转染miR-103a-3p-NC(miR-NC)和pCDH空表达载体,miR-103a-3p组细胞共转染miR-103a-3p模拟物(miR-103a-3p mimics)和pCDH空表达载体,RECK组细胞共转染miR-NC和含RECK的pCDH表达载体(pCDH-RECK),miR-103a-3p+RECK组细胞共转染miR-103a-3p mimic和pCDH-RECK。采用划痕试验检测各组细胞的迁移能力,采用Transwell实验检测各组细胞的侵袭能力,采用Western blot法检测各组细胞中RECK蛋白相对表达量。应用Starbase数据库通过生物信息分析预测miR-103a-3p与RECK的3′非翻译区(3′-UTR)是否存在结合位点,构建含有预测结合位点的野生...     

DDD-Pacemaker Pseudomalfunction During Supraventricular Tachycardia

Asynchronous pacing during the presence of electromagnetic interference or other sources of "noise" is a protective mechanism available to prevent pacemaker output inhibition. We describe a patient with a DDD pacemaker who had asynchronous dual chamber or noise reversion pacing as a consequence of repetitive signals (QRS complexes) falling into the noise sampling period (NSP) of the pacemaker ventricular refractory period. During supraventricular tachycardia at a rate of 215 bpm, noise reversion mode pacing occurred when QRS complexes were well detected immediately after the termination of a normal pacemaker ventricular refractory period and treated as a premature ventricular depolarization, resulting in automatic refractory period extension. Recycling of this extended refractory period occurred when consecutive QRS complexes were detected during the NSP and forced asynchronous dual chamber pacing at the programmed lower rate. The mechanism is presented and was supported by subthreshold esophageal pacing simulating the tachycadia and initiating the noise reversion response.