国产与进口盐酸胺碘酮片体外溶出情况比较分析

目的:通过考察盐酸胺碘酮(AH)片的溶出曲线,比较AH国产与进口(参比)制剂体外溶出情况。方法:采用2010年版《中国药典》AH片项下的溶出度测定方法对2010年市场上抽验到的10个厂家的174批国产AH片的溶出曲线进行考察,对溶出参数采用相似因子法进行统计学处理并与参比制剂进行相似性比较,采用相似等效限法进行批间溶出重现性和批内溶出均一性考察。结果与结论:与参比制剂比较,10个厂家的产品只有2家产品的溶出曲线与其相似,其余产品差异较大;10个厂家的产品有5家批间重现性不好,有4家批内均一性不好。参比制剂的体外溶出情况较国产片更优,发生差异的原因主要与处方组成及工艺有关。     

长期应用恩替卡韦治疗的慢性乙型肝炎患者耐药发生情况及原因分析:8年随访研究

目的:了解慢性乙型肝炎患者长期应用恩替卡韦(ETV)治疗的耐药发生情况并探讨耐药原因。方法:对2003-2007年3月参加ETV剂量和疗效的随机双盲Ⅱ期临床试验、ETV与拉米夫定(LAM)治疗慢性乙型肝炎的随机双盲对照Ⅲ期临床试验、ETV治疗LAM失效的慢性乙型肝炎Ⅲ期临床试验及其后续ETV开放治疗临床试验的63例慢性乙型肝炎患者继续给予治疗和随访,计算截至2011年3月的累积耐药发生率,对临床耐药患者进行乙型肝炎病毒(HBV)逆转录酶区(RT)序列突变检测,并分析耐药原因。结果:63例患者中3例治疗2年后失访;1例治疗2.5年时转其他中心治疗;其他59例中16例用药4～6年,43例用药7～8年,随访4～8年,中位随访时间7年。13例患者发生临床耐药,累积耐药发生率为20.5%。9例耐药患者进行了HBV RT序列突变检测,其中5例检测出LAM耐药位点L180M和M204V突变和1～2个ETV耐药位点突变,符合ETV耐药特点;3例仅检出LAM耐药位点突变;1例检出2个ETV耐药位点突变和ADF耐药位点A181T突变。LAM经治、治疗前高病毒载量、治疗6个月病毒学应答不佳、治疗依从性差可能与耐药的发生有关。结论:长期应用恩替卡韦治疗慢性乙型肝炎耐药率较低。对治疗初期应答不佳患者,加强监测和提高治疗依从性可减少耐药的发生。     

离子色谱法测定托吡酯原药中氨基磺酸盐和硫酸盐

建立了离子色谱法测定托吡酯原药中的降解物氨基磺酸盐和硫酸盐。采用电导检测器和A Supp 7-250阴离子分析柱,以碳酸钠(5.0 mmol/L)-碳酸氢钠(3.0 mmol/L)溶液∶丙酮(95∶5)为淋洗液。氨基磺酸根和硫酸根在0.5~20.0μg/ml浓度范围内线性关系良好,回收率为100.4%和101.5%,RSD均为0.7%。     

稳定性心绞痛患者PCI围手术期血浆超敏C反应蛋白与血管再狭窄

目的：探讨超敏C反应蛋白（hs-CRP）在稳定性心绞痛患者PCI围手术期中的变化与术后再狭窄的关系。方法：分析78例稳定性心绞痛患者临床资料,分析其在PCI术前、术后即刻、术后24 h、术后72 h及复查冠脉造影前的超敏hs-CRP水平;术后6个月行冠脉造影复查后分为再狭窄组（10例）及无再狭窄组（68例）;比较两组hs-CRP水平。结果：再狭窄组与无再狭窄组比较,两组各项临床特征差异无统计学意义;PCI术后所有患者的hsCRP水平与术前相比均有明显升高,而且再狭窄组患者术后72 h hs-CRP水平高于无再狭窄组（9.81±4.76 vs6.64±2.89,P〈0.01）,术后24 h时再狭窄组hs-CRP水平高于无再狭窄组（3.77±1.52 vs 2.43±1.05,P〈0.05）。结论：稳定性心绞痛患者PCI术后24 h、72 h时hs-CRP明显增高时,提示患者可能出现支架内再狭窄。     

Design,synthesis and activity evaluation of novel pyridinone derivatives as anti-HIV-1 dual (RT/IN) inhibitors

Three series of novel anti-immunodeficiency virus 1 (HIV-1) dual (RT/IN) inhibitors were rationally designed by introducing a functioning diketo acid (DKA) into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance (SPR), and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.     

Light Emitting Diodes Irradiation Regulates miRNA-877-3p to Promote Cardiomyocyte Proliferation

Mammalian cardiomyocytes (CMs) maintain a low capacity for self-renewal in adulthood, therefore the induction of CMs cycle re-entry is an important approach to promote myocardial repair after injury. Recently, photobiomodulation (PBM) has been used to manipulate physiological activities of various tissues and organs by non-invasive means. Here, we demonstrate that conditioned PBM using light-emitting diodes with a wavelength of 630 nm (LED-Red) was capable of promoting the proliferation of neonatal CMs. Further studies showed that low-power LED-Red affected the expression of miR-877-3p and promoted the proliferation of CMs. In contrast, silencing of miR-877-3p partially abolished the pro-proliferative actions of LED-Red irradiation on CMs. Mechanistically, GADD45g was identified as a downstream target gene of miR-877-3p. Conditioned LED-Red irradiation also inhibited the expression of GADD45g in neonatal CMs. Moreover, GADD45g siRNA reversed the positive effect of LED-Red on the proliferation of neonatal CMs. Taken together, conditioned LED-Red irradiation increased miR-877-3p expression and promoted the proliferation of neonatal CMs by targeting GADD45g. This finding provides a new insight into the role of LED-Red irradiation in neonatal CMs biology and suggests its potential application in myocardial injury repair.     

乙型肝炎肝硬化并发急性肾损伤患者临床特点及其危险因素分析

目的 分析总结乙型肝炎肝硬化患者并发急性肾损伤(AKI)的临床特点及其危险因素.方法 2015年4月～2020年2月我院收治的乙型肝炎肝硬化患者223例,采用ELISA法检测血清α羟丁酸脱氢酶(HBDH),使用分光光度计检测吲哚氰绿(ICG),采用简化的美国肾脏病膳食改善(MDRD)研究组发布的公式计算估算的肾小球滤过...     

Emerging trends in sacubitril/valsartan research: A bibliometric analysis of the years 1995–2021

Background:Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan.Methods:Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA).Results:A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015–2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. “Heart failure” was the leading research hotspot. The keywords, “inflammation,” “fibrosis,” and “oxidative stress” appeared most recently as research fronts.Conclusions:Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined.     

血清心肌肌钙蛋白Ⅰ的检测对慢性肺源性心脏病患者诊断治疗的临床意义

目的 探讨心肌肌钙蛋白Ⅰ(cardiac tropnin-Ⅰ,CTNI)检测对慢性肺源性心脏病(chronic pulmonary heart disease,CPHD)患者诊疗的临床意义.方法 检测30例CPHD患者、30例慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者急性加重期和缓解期以及20名健康者外周血清CTNI水平.结果 CPHD患者急性加重期血清CTNI为(0.02±0.49) μg/L,缓解期为(0.00±0.00) μg/L,认为CPHD患者急性加重期和缓解期血清CTNI水平差异有统计学意义(P＜0.001);COPD患者急性加重期和缓解期血清CTNI均为(0.00士0.00) μg/L,COPD患者急性加重期和缓解期血清CTNI水平差异无统计学意义(P＞0.05);CPHD患者急性加重期血清CTNI为(0.02±0.49) μg/L,COPD患者急性加重期血清CTNI(0.00±0.00) μg/L,认为CPHD患者急性加重期和COPD患者急性加重期血清CTNI水平差异有统计学意义(P＜0.001).结论 CPHD患者急性加重期存在心肌损伤,血清CTNI增高可作为CPHD患者急性加重期心肌损伤的指标之一.测定血清CTNI对及时了解CPHD患者心肌损害程度、改善疗效有重要的临床意义.     

高钾饮食对大鼠肾脏WNK1不同转录本表达的作用及其意义

背景 WNK1是新近发现的肾脏多个离子转运体及通道的调控蛋白,与醛固酮离子转运途径有关.目的 探讨高钾饮食致体内醛固酮增高对大鼠肾脏WNK1不同转录本表达的作用及其意义.方法 采用高钾饮水饲养Wistar大鼠8只,检测血清、24 h尿液离子质量浓度及血清醛固酮质量浓度.半定量RT-PCR方法 检测大鼠肾脏WNK1-L和WNK1-KS基因表达情况.结果 与正常对照组(n=8)比较,高钾组(n=8)血清醛固酮水平显著升高[(1.86±0.66)比对照组:(0.25±0.04)μg/L,P<0.01],为对照的7.4倍.血清及尿液钾离子和尿液氯离子质量浓度升高(P<0.05),尿液钠离子质量浓度下降(P<0.05),血清钠离子和氯离子无差异(P>0.05).高钾组WNK1-L表达量无差异(0.27±0.07比0.26±0.07,P>0.05),WNK1-KS表达量显著上升(1.60±0.22比0.38±0.08,P<0.01).结论 高钾饮食导致大鼠醛固酮质量浓度升高,醛固酮可通过调控WNK1-KS表达起到排钾保钠的生理作用.