基于重水拉曼技术评价口腔抑菌剂对粪肠球菌抑菌效能的研究

目的:开发有效且对患者副作用小的口腔抑菌剂配方,系统评价过氧化氢(hydrogen peroxide,H2O2)、次氯酸钠(Sodium hypochlorite,NaClO)对粪肠球菌(Enterococcus faecalis ATCC29212)的抑菌效能.方法:分别采用肉汤稀释法和重水拉曼技术(D2O-labeled single-cell Raman micro-spectroscopy),通过最小抑菌浓度(minimum inhibitory concentration,MIC)和最低抑制代谢浓度(minimum inhibitory concentration based on metabolic activity,MIC-MA)定量评价了抑菌剂对粪肠球菌的生长和代谢抑制作用.结果:对于过氧化氢和次氯酸钠,MIC分别为110 mg/L和0.45 g/L,尽管生长完全停止,但细菌细胞的代谢活性在8 h平均降低了71％、70％,显示出一种"非生长但代谢活跃"(NGMA)的状态,这种状态可能导致潜在的难治性反复感染.而MIC-MA分别为220 mg/L和0.9 g/L时,所有细胞的代谢活动在暴露8 h后完全停止.此外,NaClO+H2O2的组合使用优于单独使用次氯酸钠、过氧化氢.结论:MIC-MA有利于严格评估抗细菌疗效,NaClO+H2O2可作为细菌病原体更有效的抑菌剂方案.     

Quantitative Estimation of Plasma Free Drug Fraction in Patients With Varying Degrees of Hepatic Impairment: A Methodological Evaluation

Quantitative prediction of unbound drug fraction (f_u) is essential for scaling pharmacokinetics through physiologically based approaches. However, few attempts have been made to evaluate the projection of f_u values under pathological conditions. The primary objective of this study was to predict f_u values (n = 105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein associated with differing levels of hepatic dysfunction. For the purpose of scaling, data pertaining to albumin and α1-acid glycoprotein levels in response to differing degrees of hepatic impairment were systematically collected from 919 adult donors. The results of the present study demonstrate for the first time the feasibility of physiologically based scaling f_u in hepatic dysfunction after verifying with experimentally measured data of a wide variety of compounds from individuals with varying degrees of hepatic insufficiency. Furthermore, the high level of predictive accuracy indicates that the inter-relation between the severity of hepatic impairment and these plasma protein levels are physiologically accurate. The present study enhances the confidence in predicting f_u in hepatic insufficiency, particularly for albumin-bound drugs.     

Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors from Hypericum japonicum

Kaposi''s sarcoma associated herpesvirus (KSHV) has gained considerable attention as a type of carcinogenic pathogen. Recent research suggests that KSHV has participated in the pathogenesis of Kaposi''s sarcoma-related malignant neoplastic diseases. Viral lytic infection might be pivotal for the etiopathogenesis of KSHV-induced diseases; however, most clinical KSHV lytic replication inhibitors like ganciclovir, nelfinavir, or cidofovir do not restrain virus replication effectively enough to achieve clinical efficacy. In our continued pharmaceutical studies on Chinese herbal medicines, new acylphloroglucinol-based meroterpenoid enantiomers have been discovered from Hypericum japonicum. Most of these metabolites have potential inhibitory activities that target KSHV lytic replication. Amongst these analogues, compounds 1a and 1b possess an unreported ring system cyclopenta[b]chromene. Compounds 1a with 4a exhibit stronger inhibitory activities towards the lytic replication of KSHV in Vero cells. In addition, 1a and 4a have IC₅₀ values of 8.30 and 4.90 μM and selectivity indexes of 23.49 and 25.70, respectively. Qualitative and quantitative SAR and molecular docking studies for acylphloroglucinol-based meroterpenoids with regard to anti-KSHV activity were conducted. An explanation for the variation in the activity and selectivity indexes was proposed in accordance with the predicted binding pose found with molecular docking to a putative target, thymidylate synthase (kTS). Compounds 1a and 4a have potential for further development and optimization of their anti-KSHV activities which could lead to new candidate drugs.

New enantiomers (1a/1b–4a/4b) were discovered from Hypericum japonicum. 1a/1b possessed a novel ring system cyclopenta[b]chromene. 1a and 4a exhibited promising anti-KSHV activities. QSAR studies for enantiomers on anti-KSHV activity were conducted.     

Safety assessment of aditoprim acute,subchronic toxicity and mutagenicity studies

Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD₅₀ calculated was 1400 mg kg^–1 body weight (BW) day^–1 in rats and 1130 mg kg^–1 BW day^–1 in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg^–1 diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high‐dose group. Treatment‐related changes in clinical serum biochemistry were found in the medium‐ and high‐dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg^–1 diet, and significant decrease in relative weights of livers in males in the 100 mg kg^–1 diet were noted. Histopathological observations revealed that the 1000 mg kg^–1 ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no‐observed‐adverse‐effect level for ADP was a 20 mg kg^–1 diet, which is about 1.44‐1.53 mg kg^–1 BW day^–1 in rats. Copyright © 2015 John Wiley & Sons, Ltd.     

The effect of prenatal education curriculum on mother’s prenatal examination utilization,delivery mode and recovery status: a cross-sectional survey in China

ObjectivesTo examine the participation, implementation, and effect of the prenatal education curriculum provided by hospitals in China, and to provide evidence for the improvement of prenatal education.MethodsA cross-sectional survey was conducted in the hospitals in Hunan Province, China. Mothers aged 20–45 years who had given birth between 1 May 2011 and 1 May 2012 and not diagnosed with pregnancy-related complications were invited to participate in the study. A self-administered, structured questionnaire was used to examine the effect of prenatal education curriculum on prenatal examination utilization, delivery mode, and recovery status from delivery.ResultsAmong the total 604 respondents, only 175 (29.1 %) surveyed mothers participated in prenatal education curriculum provided by hospitals during their latest delivery. These mothers had a higher rate of attending all the required prenatal examinations (57.9 vs. 48.3 %), and a higher rate of recovering very well and well (80 vs. 73.7 %) from the latest delivery, than those who did not participate in prenatal education curriculum (P < 0.05). However, there was no statistical difference in the delivery mode between mothers who participated and those who did not participate in the prenatal education curriculum provided by hospitals.ConclusionsPrenatal education is indispensable for the improvement of maternal and child health, and thus should be advocated. In China, a standard and convenient specification prenatal education curriculum provided by hospitals and their doctors is appropriated for providing prenatal education to pregnant women.     

四川省西部山区农村寄宿制学校食育干预效果评价

目的通过对四川省西部山区农村寄宿制学校学生进行食育干预,提高学生的营养健康知识和技能,培养其科学的饮食习惯。方法整群抽取四川省蒲江县长秋山区农村寄宿制学校3所,并随机分为食育教育模式干预学校、普通营养教育对照学校及空白对照学校,研究对象为3所学校的2~8年级全部学生。结果经过1年时间的干预,食育干预学校学生营养健康知识知晓率有明显改善,"清楚知道《中国居民膳食宝塔》每层食物的"的知晓率上升最明显,相比基线调查上升了59.1%,高于对照组;在态度方面,食育干预学校学生喜欢吃含糖饮料的下降了19.0%;在行为方面,"学生购买食物前经常看营养标签"的上升了22.8%,"最近1周每天吃早餐"的上升了22.8%,均高于对照组。结论食育干预对学生的营养健康态度、食物喜好改变,还是饮食及健康相关行为方面的改善效果明显,而且食育干预效果优于普通营养教育对照学校。     

高效液相色谱法测定新生儿体内氟康唑的血药浓度

目的：建立测定新生儿体内氟康唑血药浓度的高效液相色谱（HPLC）法。方法：HPLC色谱条件为色谱柱Diamonsil C18柱（5 μm,4.6mm×250 mm）;流动相甲醇﹕磷酸盐缓冲液（pH 7.0）=45︰55;检测波长261 nm;流速1 mL/min;柱温30℃;进样量10 μL。供试品溶液的制备,取样品加入内标后用乙酸乙酯萃取,有机相用氮气吹干,以甲醇溶解,进样测定。结果：该方法氟康唑在1.0~50.0 μg/mL范围内有良好线性关系,精密度、稳定性及回收率较好。结论：该方法操作简单、重复性好、准确可靠,可作为新生儿体内预防用氟康唑HPLC含量测定的方法。     

Novel long noncoding RNA LINC02323 promotes cell growth and migration of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p

BackgroundThis study was aimed at investigating the effects of long noncoding RNA (lncRNA) LINC02323 in ovarian cancer and its possible mechanism.MethodsMicroarray analysis and QPCR were utilized to identify lncRNA LINC02323 expression in patients with ovarian cancer. MTT assay was used for analysis of ovarian cancer cell proliferation. Western blot was utilized to investigate its possible mechanism.ResultsIn patients with ovarian cancer, lncRNA LINC02323 expression was up‐regulated and miR‐1343‐3p expression was down‐regulated. Over‐expression of lncRNA LINC02323 promoted cell growth and reduced LDH activity levels in vitro model by suppression of miR‐1343‐3p expression. Down‐regulation of lncRNA LINC02323 reduced cell growth and increased LDH activity levels in vitro model by induction of miR‐1343‐3p expression. Over‐expression of miR‐1343‐3p reduced cell growth and reduced LDH activity levels in vitro model by suppression of TGF‐β receptor. Down‐regulation of miR‐1343‐3p promoted cell growth and reduced LDH activity levels in vitro model by induced of TGF‐β receptor.ConclusionOur findings show that Novel long noncoding RNA LINC02323 promotes cell growth of ovarian cancer via TGF‐β receptor 1 by miR‐1343‐3p.