香豆雌酚对膝骨关节炎患者软骨细胞OPG/RANKL及MMP-1、MMP-3表达的影响

目的:研究香豆雌酚(coumestrol)对膝骨关节炎患者软骨细胞OPG/RANKL及MMP-1、MMP-3表达的影响,初步探讨其对骨关节炎的治疗机制。方法:分离、培养因膝骨关节炎行膝关节置换患者的膝关节软骨细胞,运用Ⅱ型胶原免疫荧光染色进行软骨细胞鉴定。用不同浓度(10-9、10-8、10-7mol·L-1)香豆雌酚干预第3代细胞,并设0浓度为空白对照组,分别于培养后3、7 d用real-time PCR法测定细胞骨保护素(osteoprotegerin,OPG)、核因子κB受体活化因子配基(receptor activator of nuclear factor-κB ligand,RANKL)、基质金属蛋白酶-1(matrix metalloproteinase-1,MMP-1)和基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)mRNA的表达。结果:干预3 d,10-8mol·L-1组OPG及RANKL mRNA表达均增加,其OPG/RANKL相对表达是空白对照组的2.59倍(P<0.05);干预7 d,10-9和10-8mol·L-1组OPG mRNA表达均增加,10-7mol·L-1组RANKL mRNA表达增加,10-8mol·L-1组OPG/RANKL相对表达是空白对照组的3.85倍(P<0.05)。干预3 d,10-8mol·L-1组MMP-1 mRNA表达减少(P<0.05);干预7 d,10-8mol·L-1组MMP-1和MMP-3 mRNA表达均减少(P<0.05)。结论:香豆雌酚能增加膝骨关节炎患者关节软骨细胞OPG表达及OPG/RANKL值,减少其MMP-1、MMP-3表达,具有一定的软骨保护作用。     

干扰素联合拉米夫定治疗YMDD变异株慢性乙型肝炎

新一代核苷类似物拉米夫定作为抗乙型肝炎病毒(HBV)感染的有效药品用于临床已取得了较好疗效，但因YMDD变异株的出现，又使部分慢性乙型肝炎(CHB)的治疗复杂化。目前尚无理想的抗YMDD变异病毒治疗方案，我们用干扰素联合拉米夫定治疗YMDD变异株CHB近两年，效果比较满意。     

Identification and characterization of novel synthetic cannabinoid ethyl-2-(1-(5-fluoropentyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (5F-EDMB-PICA)

Forensic Toxicology - The purpose of the current study was to evaluate an analytical characterization of a novel synthetic cannabinoid...     

177Lu-FA-DOTA-PEG-PLGA靶向可降解纳米粒子腹腔灌注治疗小鼠卵巢癌伴腹膜转移的实验研究

目的 观察放射性核素¹⁷⁷Lu标记的叶酸-二乙烯三胺五乙酸-聚乙二醇-聚乳酸共聚物(¹⁷⁷Lu-FA-DOTA-PEG-PLGA)纳米粒子的体内靶向分布,评价腹腔灌注纳米粒子治疗小鼠卵巢癌腹膜转移瘤及腹水疗效。方法 制备¹⁷⁷Lu-FA-DOTA-PEG-PLGA纳米粒子,向人卵巢癌移植瘤荷瘤小鼠尾静脉注射纳米粒子后4、24、72 h和7 d,行微型单光子发射计算机断层显像仪(micro-SPECT/CT)显像,观察纳米粒子体内分布情况。将12只人卵巢癌腹腔转移瘤裸鼠模型按随机抽签法分为阴性对照组(生理盐水)、化疗组(顺铂3 mg/kg,2次/周)和粒子组(¹⁷⁷Lu-FA-DOTA-PEG-PLGA粒子18.5 MBq),每组4只,腹腔灌注给药。7 d后行活体荧光成像评价腹腔肿瘤生长情况,计算相对抑瘤率,TUNEL法检测肿瘤细胞凋亡率,免疫组织化学法检测肿瘤Ki67增殖活性,比较治疗后各组腹水体积。结果 micro-SPECT/CT显像显示,移植瘤放射性浓聚,24 h肿瘤肌肉摄取比值(T/M)最高,为2.81±0.49。活体荧光成像显示,腹腔给药治疗后,粒子组、化疗组和阴性对照组的腹腔肿瘤荧光强度分别为(1.45±0.19)×10¹⁰、(2.21±0.36)×10¹⁰和(2.63±0.79)×10¹⁰,差异有统计学意义(F=6.09,P=0.029);粒子组和化疗组的相对肿瘤抑制率(TGI)分别为35.6%和18.6%。粒子组和化疗组的肿瘤细胞凋亡率(AI)均高于阴性对照组(F=9.96,P=0.009),粒子组和化疗组的Ki67指数均低于阴性对照组(F=9.93,P=0.013),粒子组和化疗组腹水体积均小于阴性对照组(F=13.43,P=0.006)。结论 ¹⁷⁷Lu-FA-DOTA-PEG-PLGA纳米粒子可行小鼠卵巢癌靶向显像,腹腔灌注后局部滞留和降解吸收,抑制卵巢癌腹膜转移瘤和腹水生长,为晚期卵巢癌伴腹膜转移患者诊疗提供新思路。     

心房颤动的药物治疗现状和进展

心房颤动(AF)是临床常见的心律失常之一,患病率和致残致死率高,药物疗效不理想.近年来,随着对AF发生和维持机制的不断了解,特别是新药不断问世、传统药物新功能的研究,药物治疗已取得了较大进展.本文主要从心率控制、节律控制、改善心房重构和抗炎等方面加以介绍.     

天王补心丹联合丙硫氧嘧啶治疗甲状腺功能亢进的疗效观察

目的探讨丙硫氧嘧啶联合天王补心丹治疗甲状腺功能亢进患者的治疗效果。方法选取2018年1月—2019年6月许昌市人民医院收治甲状腺功能亢进患者86例,随机分为对照组和治疗组,每组各43例。对照组患者口服丙硫氧嘧啶片,初始剂量为100 mg/次,3次/d,然后依据患者甲状腺激素水平改变剂量。治疗组在对照组基础上口服天王补心丹,1丸/次,3次/d。两组患者治疗30 d。观察两组患者临床疗效,同时比较治疗前后两组患者中医证候积分,三碘甲状腺原氨酸(FT3)、四碘甲状腺原氨酸(FT4)、促甲状腺激素(TSH)和促甲状腺素受体抗体(TRAb)指标水平,及随访结果情况。结果治疗后,对照组临床有效率为79.07%,显著低于治疗组的95.35%,两组比较差异具有统计学意义(P0.05)。治疗后,两组中医证候积分均明显降低(P0.05),且治疗组降幅明显大于对照组(P0.05)。治疗后,两组患者FT3、FT4、TRAb的指标均明显下降(P0.05),而TSH指标则明显上升(P0.05),且治疗组明显好于对照组(P0.05)。随访期间治疗组患者的症状控制时间、肝脏损伤时间、TSH指标恢复正常时间均显著短于对照组(P0.05)。结论丙硫氧嘧啶联合天王补心丹治疗甲状腺功能亢进患者疗效显著,并改善患者的甲状腺激素水平,同时安全性好。     

Autophagy induction by rapamycin ameliorates experimental colitis and improves intestinal epithelial barrier function in IL-10 knockout mice

BackgroundAn impairment of the intestinal barrier function is one of the major characteristics of Crohn’s disease (CD). This study aimed to evaluate the impact of autophagy induction by rapamycin on the intestinal epithelial barrier function in CD model mice.MethodsIL-10 knockout (IL-10 KO) mice were used as the human CD models in this study. All the mice were randomly assigned into four groups, (a) wild-type (WT) group; (b) IL-10 KO group; (c) IL-10 KO + rapamycin group and (d) IL-10 KO + 3-methyladenine (3-MA), containing 6 mice in each group. The disease activity index (DAI), histology, pro-inflammatory cytokines and chemotactic factors in colon tissues, intestinal and colonic permeability, distributions and expressions of tight junction (TJ) proteins, epithelial apoptosis of mice in four groups were evaluated and compared.ResultsAutophagy induction by rapamycin treatment ameliorated DAI and histological colitis, decreased pro-inflammatory cytokines (TNF-α, IFN-γ and IL-17) and chemotactic factors (CXCL-1 and CXCL-2), decreased intestinal and colonic permeability, improved the distribution and expression of TJ proteins in IL-10 KO mice.ConclusionAutophagy induction by rapamycin significantly improved intestinal barrier function and protected IL-10 KO mice from the experimental chronic colitis.     

临床药师参与1例车祸致重症感染患者临床治疗万古霉素谷浓度不达标的原因分析

目的:分析车祸致重症感染患者万古霉素谷浓度不达标的原因,探究临床药师的药学监护过程。方法:临床药师参与万古霉素给药方案的制订,对重症感染患者开展治疗药物监测(TDM)和药学服务。结果:万古霉素的血药浓度受患者体质量、年龄、肾功能、体液量及表观分布容积等多种因素的影响。结论:万古霉素的个体差异较大,影响因素较多,临床医生和药师应对万古霉素TDM,关注其谷浓度的变化。     

经阴道常规超声联合实时超声弹性成像评估宫颈癌同步放化疗疗效

目的 观察经阴道常规超声联合实时超声弹性成像评价宫颈癌同步放化疗（CCRT）疗效的可行性。方法 收集30例经病理确诊并接受CCRT的宫颈癌患者,于CCRT前1周（治疗前）、治疗3周（治疗中）及治疗结束1个月（治疗后）行经阴道常规超声联合实时超声弹性成像检查,于治疗前及治疗后行盆腔MRI,比较治疗前、中、后各超声参数变化。依据超声及MRI表现评估宫颈癌CCRT疗效,观察二者的一致性。结果 30例宫颈癌中,28例鳞癌、2例腺癌。治疗前、中、后病灶最大径差异均有统计学意义（P均<0.01）;治疗前、后病灶回声、血流分级、弹性评分差异均有统计学意义（P均<0.01）;治疗前、中、后病灶边界、阻力指数差异均无统计学意义（P均>0.05）。治疗后12例完全缓解、18例部分缓解,经阴道常规超声联合弹性成像评估结果与MRI结果的一致性较强（Kappa=0.72,P<0.01）。结论 经阴道常规超声联合实时超声弹性成像技术可用于评估CCRT治疗宫颈癌效果。     

More attention should be paid to pregnant women who fail non-invasive prenatal screening

ObjectiveWe discuss how to handle failure of first-pass non-invasive prenatal screening (NIPS) and investigate the pregnancy outcomes after second-pass failure.MethodsA total of 35,187 pregnant women underwent NIPS in a single center. Those who failed first-pass NIPS were re-tested after a repeat blood draw. Those who failed again were offered genetic counseling. We recorded antenatal data and pregnancy outcomes.ResultsA total of 273 (0.78%) women failed the first test. On re-testing, 220 (80.59%) yielded reliable results and 53 failed the test again. Women with higher total cell-free DNA (cfDNA) levels evidenced a lower NIPS success rate (40%) and a higher incidence of adverse pregnancy outcomes.ConclusionsMost women who failed first-pass NIPS yielded reliable results on repeat testing, especially those with lower fetal fraction. Higher concentrations of cfDNA in maternal plasma were associated with poorer pregnancy outcomes. Such women require special attention, thus early medical intervention, to avoid an adverse prognosis.