Effects of Total Flavones from Acanthopanax senticosus on L‐type Calcium Channels,Calcium Transient and Contractility in Rat Ventricular Myocytes

Acanthopanax senticosus (Rupr. et Maxim.) Harms (AS), a traditional herbal medicine, has been widely used to treat ischemic heart disease. However, the underlying cellular mechanisms of its benefits to cardiac function remain unclear. The present study examined the effects of total flavones from AS (TFAS) on L‐type Ca²⁺ channel currents (I_Ca‐L) using the whole cell patch‐clamp technique and on intracellular calcium ([Ca²⁺]_i) handling and cell contractility in rat ventricular myocytes with the aid of a video‐based edge‐detection system. Exposure to TFAS resulted in a concentration‐ and voltage‐dependent blockade of I_Ca‐L, with the half‐maximal inhibitory concentration (IC₅₀) of 283.12 µg/mL and the maximal inhibitory effect of 36.49 ± 1.95%. Moreover, TFAS not only increased the maximum current in the current–voltage relationship but also shifted the activation and inactivation curves of I_Ca‐L toward the hyperpolarizing direction. Meanwhile, TFAS significantly reduced amplitudes of myocyte shortening and [Ca²⁺]_i with an increase in the time to 10% of the peak (Tp) and a decrease in the time to 10% of the baseline (Tr). Thus, the cardioprotective effects of TFAS may be attributed mainly to the attenuation of [Ca²⁺]_i through the direct inhibition of I_Ca‐L in rat ventricular myocytes and consequent negative effect on myocardial contractility. Copyright © 2015 John Wiley & Sons, Ltd.     

胎儿下肢长骨骨重的非对称性研究

作者研究胎儿下肢长骨骨重的非对称性,测量了佳未斯地区胎儿88具下肢长骨,两侧骨重相差10%为非对称性标准。结果表明:除女性腓骨外,胎儿男、女性各骨骨重侧别差异均无统计学意义,长骨骨重的非对称性占绝大多数,右侧重多于左侧重。     

罗格列酮单用或者与阿伐他汀联合使用对于2型糖尿病患者心血管疾病的非传统标志物的作用

背景和目的:罗格列酮与阿伐他汀联合疗法已经被证实对于2型糖尿病患者的血糖控制以及脂质水平都有益处。本试验将通过检测罗格列酮与阿伐他汀联合疗法对于2型糖尿病患者的生物标记水平的作用来研究该联合疗法对血管炎的作用。方法:30例患有2型糖尿病和高脂血症的患者被纳入治疗。对这些患者给予罗格列酮单一疗法4mg/d,持续3个月,然后在接下来的3个月中给予这些患者阿伐他汀10mg/d作为联合疗法。在研究开始时,罗格列酮单一疗法之后以及罗格列酮与阿伐他汀联合治疗之后测量炎性生物标记物,包括高敏C-反应蛋白(hs-CRP)、基质金属蛋白酶9(MMP…     

杏丁注射液对塌陷前期酒精性股骨头坏死患者血液流变学及影像学的影响

目的观察杏丁注射液对塌陷前期酒精性股骨头坏死患者血液流变学及影像学的影响。方法将37例塌陷前期酒精性股骨头坏死患者随机分成2组:对照组给予川芎嗪注射液120 mg+5%葡萄糖液250 mL静滴;治疗组予杏丁注射液30 mL+250 mL生理盐水或葡萄糖液静滴,均每日1次,14 d为1个疗程。观察2组治疗前后血液流变学及影像学变化。结果治疗组用药后血液流变学及骨髓水肿改善程度与疼痛缓解程度明显优于对照组。在随访过程中未发现杏丁注射液的不良反应。治疗组患者X线片示塌陷率与对照组比较无显著性差异。结论杏丁注射液可显著改变血液流变状态以及股骨头内骨髓水肿程度,可有效缓解髋部的疼痛,是治疗塌陷前期酒精性股骨头坏死的一种有效而安全的药物。     

复方丹参滴丸联合心得安对肝纤维化及门脉高压的影响

1999年6～9月，我们采用复方丹参滴丸联合心得安治疗肝炎肝硬化30例，以观察其降低门脉高压及肝纤维化程度的变化，现报告如下。     

利用条件错误发现率方法识别抑郁症和失眠症的多效性位点

背景 抑郁症和失眠症常共病存在,两者存在一些共同的发病机制,并可能受相同的多效性基因调控。既往全基因组关联研究（GWAS）一般采用单性状研究,在解释基因多效性方面存在一定的狭窄性。目的 识别与失眠症和抑郁症相关的遗传变异位点,检验抑郁症和失眠症是否存在共同的遗传因素。方法 抑郁症GWAS数据来自精神疾病遗传学联盟（PGC）,共包含246 363例抑郁症患者和561 190例正常对照。失眠症GWAS数据来自睡眠障碍知识门户,共包含1 331 010例受试者。采用条件错误发现率（cFDR）和联合的条件错误发现率（ccFDR）方法筛选与抑郁症和失眠症相关的遗传位点,采用通路富集分析检验这些位点的生物学功能。结果 抑郁症和失眠症存在显著的多效性富集现象。利用cFDR方法,以cFDR<0.01作为显著性阈值,鉴定出21个易感位点与抑郁症相关（其中17个是新识别的）,38个易感位点与失眠症相关（其中28个是新识别的）。以ccFDR<0.05为显著性阈值,识别出16个多效性位点与抑郁症和失眠症均相关,其中15个是本研究新识别的。通路富集分析结果显示,与抑郁症和失眠症均关联的易感位点富集于突触传递相关通路,如突触后密度（GO：0014069,P=4.91E-04,FDR=4.84E-03）、不对称突触（GO：0032279,P=5.09E-0,FDR=4.84E-03）、突触后膜神经递质受体水平的调节（GO：0099072,P=5.11E-04,FDR=1.69E-02）。结论 失眠症与抑郁症之间存在多效性富集现象,其共病机制与突触传递有关。     

Association Between Nap and Reported Cognitive Function and Role of Sleep Debt: A Population-Based Study

Background and PurposeThe relationship between napping and cognition remains controversial. This study aimed to investigate the association between napping and cognition according to sleep debt in the Korean adult population.MethodsA population-based nationwide cross-sectional survey was conducted in 2018. A two-stage stratified random sample of Koreans aged ≥19 years was selected and evaluated using questionnaires by trained interviewers. Cognitive function was assessed using the Mail-In Cognitive Function Screening Instrument (MCFSI). Sleep habits on weekdays and weekends, napping, and subjective sleep requirements were assessed using the questionnaires. Accumulated sleep debt was calculated by subtracting the weekly average sleep duration from subjective sleep requirements. Sleep quality, daytime sleepiness, insomnia, depression, demographics, and comorbidities were assessed. Participants were grouped into those with sleep debt ≤60 min and those with sleep debt >60 min. Multiple linear regression was used to estimate the independent association between the factors and cognition.ResultsIn total, 2,501 participants were included in the analysis. Naps were reported in 726 (29.0%) participants (nappers). The mean MCFSI score was higher in nappers (3.4±3.6) than in non-nappers (2.3±3.0) (p<0.001). Multiple linear regression controlling for age, alcohol, smoking, depression, insomnia, daytime sleepiness, sleep quality, and education revealed that 30 to 60 min of napping was associated with worse cognitive function in participants with sleep debts ≤60 min, while >60 min of napping was associated with better cognitive function in participants with sleep debts >60 min.ConclusionsIn general, naps are associated with worse cognitive function in the Korean adult population. However, for those with sleep debt of >60 min, naps for >60 min were associated with better cognitive function.     

Design,Synthesis, Biological Evaluation,and Molecular Docking of Novel Benzopyran and Phenylpyrazole Derivatives as Akt Inhibitors

By inspiration of good Akt1 inhibitory and cytotoxic activity of our previously screened hits 1 and 2 , a series of novel benzopyrans 3a – c , 4 and phenylpyrazoles 5a – c , 6a – b , and 7 were designed, synthesized, and biologically evaluated for their in vitro Akt1 inhibitory and cytotoxic activity. The results revealed that all of these compounds showed moderate‐to‐excellent antiproliferative effects against the tested cancer cell lines (i.e. HL‐60, OVCAR, PC‐3, and HepG2). Among them, compounds 3a and 3c exhibited preferable Akt1 inhibitory activities (IC₅₀ of 3a and 3c are 6.18 and 5.28 μm , respectively), while compounds 4 , 5a – c , 6a – b , and 7 only showed weak Akt1 inhibitory activities. Consequently, we used molecular docking and dynamic simulation to propose a mode of binding between Akt1 and the 3c compound.     

骨化三醇对腹透患者钙磷代谢及T淋巴细胞亚群的影响

目的 :了解骨化三醇 (1 ,2 5 (OH) 2 D3 ,罗钙全 )对腹膜透析患者钙磷代谢及免疫功能的影晌。方法 :观察 3 7例腹膜透析 (PD)患者服用骨化三醇前后血清T细胞亚群、IL 8以及血免疫反应甲状旁腺激素 (iPTH)、钙、磷水平变化。结果 :用药前PD组血清T淋巴亚群的CD4/CD8低于正常对照组 (P<0 .0 5 ) ,服用骨化三醇 4wk后 ,CD4/CD8从 0 .5 6±0 .1 0升至 0 .79± 0 .1 2 ;而iPTH显著降低 ,血钙显著升高 ,血磷明显下降。结论 :骨化三醇能改善PD患者钙磷代谢 ,进而改善其免疫功能     

Dry powder inhalations containing thymopentin and its immunomodulating effects in Wistar rats

Thymopentin (TP5), a synthetic pentapeptide, has been used in clinic as a modulator for immunodeficiences through intramuscular administration. The purpose of this study was to design and evaluate dry powder inhalations (DPIs) for pulmonary delivery of TP5. Dry powder inhalations containing leucine (a dispersibility enhancer), mannitol, and lactose (bulking agents) were prepared by spray-drying from aqueous formulations. The formulation components on the aerosolisation characteristics of spray-dried powders were investigated through the use of various amount of leucine, lactose and mannitol. Following spray-drying, resultant powders were characterized using scanning electron microscopy, laser diffraction and tapped density measurements, and the aerosolisation performance was determined using Twin Stage Impinger. The immunosuppression Wistar rats model was constructed to evaluate the immunomodulating effects of TP5 DPIs in vivo. The results of T-lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+ ratio) analyses suggest that TP5 DPIs have modulating effects. On an overall evaluation, TP5 pulmonary delivery DPIs may be feasible for the future clinical application.