Metabolism of the new synthetic cannabinoid EG-018 in human hepatocytes by high-resolution mass spectrometry

Purpose

The present study aims to recommend appropriate urinary marker metabolites for documenting EG-018 consumption by investigating its metabolism in human hepatocytes.

Methods

For metabolite profiling, 10 µM EG-018 was incubated in human hepatocytes for 3 h. Metabolite identification in hepatocyte samples was accomplished with high-resolution mass spectrometry via information-dependent data acquisition.

Results

EG-018 was highly metabolized in human hepatocytes. A total of eight metabolites were characterized, mainly generated from hydroxylation and carbonylation on the pentyl chain. Dihydrodiol formation, N-dealkylation, and glucuronidation of hydroxylated metabolites were the other major pathways.

Conclusions

The primary metabolites of EG-018 in human hepatocyte incubation were pentyl hydroxylated EG-018 (M6) and pentyl carbonylated EG-018 (M8). These two metabolites are proposed as the best urinary markers for confirming EG-018 intake.

     

危重脑出血患者短期临床结局的相关因素分析

目的 探究危重脑出血患者短期临床结局的相关因素.方法 回顾性分析2016年3月至2019年8月本院ICU收治的109例重症脑出血患者的临床资料,对影响发病后30 d相关危险因素进行单因素分析及Logistic回归分析,评估患者预后情况.结果 109例脑出血患者中,结局良好59例,结局不良50例;年龄≥75岁、收缩压≤110 mmHg或≥200 mmHg、血肿体积≥30 cm3、血肿破入脑室是影响危重脑出血预后的相关危险因素.结论 通过分析临床危重脑出血相关危险因素,予以相应干预措施,可进一步改善患者预后,降低不良预后发生率,值得临床推广应用.     

Research on Curing Water Demand of Cementing Material System Based on Hydration Characteristics

The performance of cover concrete is acknowledged as a major factor governing the degradation of concrete structures. Curing plays a vital role in the development of concrete durability. The effects of different water-binder ratios and mineral admixtures on the curing water demand of concrete were studied by the surface water absorption test. Combined with the characteristics of the hydration heat and chemically bound water of the composition cementing material system, the law of variation for curing water demand was analyzed. The results show that the addition of mineral admixtures can reduce the early hydration rate and hydration exothermic characteristics, and the hydration degree decreases with the increase of mineral admixtures. Due to the filling effect and active effect, the addition of fly ash (FA) and ground granulated blast slag (GGBS) reduces the curing water demand. The curing water demand of cover concrete decreases with the increase of mineral admixture content, and the curing water demand of pure water is the maximum and that of mix FA and GGBS is the minimum. Moreover, there is a strong correlation between the cumulative curing water demand and the chemically bound water content, indicating that the power of water migration mainly comes from the hydration activity of the cementing material system. The results provide a theoretical basis for the fine control of a concrete curing system.     

自体心包行主动脉窦部重建治疗A型主动脉夹层根部的近期疗效

目的 探讨自体心包行主动脉窦部重建在治疗A型主动脉夹层根部的近期疗效.方法 选取郑州大学第一附属医院2018年1月至2020年3月42例根部运用自体心包行窦部重建的A型主动脉夹层患者,回顾性分析患者的围手术期和随访资料,对术前、出院时和术后1 a的心脏超声指标进行统计学分析.结果 患者院内死亡3例,治愈出院39例,所有...     

慢性心力衰竭伴轻度认知障碍中医证素与认知功能的相关性研究

目的：探讨慢性心力衰竭(CHF)患者中医证候要素与认知功能的相关性。方法：选取2021年5月至2022年3月北京中医药大学东方医院收治的94例CHF伴轻度认知功能障碍(MCI)患者作为研究对象,进行中医证候要素辨证,记录患者的一般资料,采用蒙特利尔认知评估量表(MoCA)对患者的认知功能进行评估,最后对中医证候要素与各项认知功能进行比较。结果：气虚证患者的视空间与执行能力评分更低,血瘀证患者的MoCA总分、注意与计算能力评分更低,痰浊证患者的MoCA总分、延迟回忆力以及抽象思维评分更低。结论：气虚证患者更容易出现视空间与执行能力的下降,血瘀证患者更容易出现注意与计算能力的下降,痰浊证患者更容易出现延迟回忆力和抽象思维能力的下降。     

小儿腹腔结核高频超声表现

目的观察儿童腹腔结核高频超声表现。方法回顾性分析26例28天～16岁腹腔结核患儿高频超声声像图表现。结果高频超声声像图显示广泛性肠管壁增厚20例,广泛性壁层腹膜不均匀性增厚24例,15例腹腔、腹膜后淋巴结肿大,10例腹腔内见多个透声差的囊性包块,2例肝脾大、2例单肾体积增大,8例大量腹腔积液、4例中量、14例少量;胰腺均未见特殊改变。结论儿童腹腔结核以增殖和干酪病变为主,其高频超声表现有一定特异性,有助于早期诊断。     

海洛因依赖者的个性心理特征及其对复吸的影响分析

目的了解自愿戒毒的海洛因依赖者的个性心理特征及其对脱毒后复吸的影响。方法使用MMPI对30例自愿戒毒的海洛因依赖者和30例未对任何药物成瘾的正常人的个性心理特征进行对照分析，明确海洛因依赖者个性心理特征，在此基础上找出个性心理特征与复吸原因的联系。结果海洛因依赖者在MMPI各量表中诈病(F)，精神病态(Pd)，疑病症(Hs)，偏执狂(Pa)，精神分裂(Sc)等量袁与对照组有明显的差异，且这些差异与脱毒者复吸原因有着直接的关系。结论海洛因依赖者的个性心理特征为明显的反社会行为和社会适应障碍，对自己健康过分关注，缺乏对社会环境的归属感，易将自己的问题合理化而归因于剐人，并由这种心理特征增加了复吸率。     

UPLC法同时测定柴胡疏肝散水煎液冻干物中8个成分的含量

目的:建立柴胡疏肝散水煎液冻干物中8个成分含量同时测定的方法。方法:采用超高效液相色谱法对6批柴胡疏肝散水煎液冻干物样品中8个成分芍药内酯苷、芍药苷、阿魏酸、柚皮苷、橙皮苷、苯甲酰芍药苷、甘草酸、α-香附酮进行含量测定。色谱柱为Phenomenex,流动相为0.1%甲酸水-乙腈梯度洗脱,检测波长为250 nm,柱温为30℃,流速为1 mL/min,进样体积为10μL。结果:芍药内酯苷、芍药苷、阿魏酸、柚皮苷、橙皮苷、苯甲酰芍药苷、甘草酸、α-香附酮的检测质量浓度线性范围分别3.606~8.414、23.988~55.972、1.218~2.842、35.964~83.916、12.009~28.021、1.194~2.786、3.609~8.421、5.294~12.352μg/mL(r=0.999 5~0.999 9),定量限分别为0.206、0.178、0.256、0.168、0.196、0.242、0.268、0.157μg/mL;精密度试验、稳定性试验(12 h)、重复性试验中的RSD均<2%(n=5或6),回收率分别为97.93%、98.18%、96.57%、97.61%、98.51%、97.45%、98.14%、96.91%(RSD均<2%);6批样品中芍药内酯苷、芍药苷、阿魏酸、柚皮苷、橙皮苷、苯甲酰芍药苷、甘草酸的平均含量分别为59.258、429.237、23.173、625.847、200.424、15.048、67.620μg/g,α-香附酮因具有挥发性未检测出。结论:建立的含量测定方法简便,结果稳定、可靠、准确,可为柴胡疏肝散水煎液冻干物的质量控制提供参考。     

复方枣仁安神胶囊中黄连的定性鉴别和定量分析

目的:建立复方枣仁安神胶囊中黄连质量标准。方法:采用薄层色谱鉴别法对黄连进行定性鉴别,采用UPLC法测定黄连中盐酸小檗碱的含量。色谱条件:色谱柱:Waters Acquity UPLC BEH C18(2.1 mm×100 mm,1.7m);流动相:乙腈-0.05 mo L·L-1磷酸二氢钾溶液(30∶70)(0.5%三乙胺,磷酸调p H值至3.0~4.0);检测波长为345 nm;流速:0.25 m L·min-1;柱温:25℃。结果:在试验条件下,薄层斑点清楚,阴性无干扰,分离效果较好,重复性良好。UPLC方法学考察表明,制剂中盐酸小檗碱在0.25~1.50g范围内与峰面积呈良好的线性关系(r=0.9999),平均回收率为97.56%,RSD=1.54%(n=6)。结论:该方法准确、快速,重复性好,可用于复方枣仁安神胶囊中黄连的质量控制。     

Lenvatinib enhances antitumor immunity by promoting the infiltration of TCF1+ CD8+ T cells in HCC via blocking VEGFR2

Lenvatinib is the favorable treatment for advanced hepatocellular carcinoma (HCC), and it is currently undergoing phase III clinical trials. However, the specific effects of lenvatinib on PD1⁺ CD8⁺ T cells in HCC microenvironment have not been systematically studied. Here, we established an orthotopic hepa1-6 mouse model treated with lenvatinib to investigate CD8⁺ T cells’ role in the tumor and spleen. We found an increasing proportion of TCF-1⁺ in PD1⁺ CD8⁺ T cells and proliferation of PD1⁺ CD8⁺ T cells after lenvatinib treatment. Meanwhile, lenvatinib treatment upregulated the expression of granzyme B on PD1⁺ CD8⁺ T cells both in vitro and in vivo. Lenvatinib activated the endogenous mTOR pathway of exhausted CD8⁺ T cells, and mTOR pathway blockade eliminated the antitumor effect of lenvatinib and function of PD1⁺ CD8⁺ T cells. The effects of the mTOR pathway on PD1⁺ CD8⁺ T cells after lenvatinib treatment were mediated by VEGFR2 inhibition. Overall, our work provides insight into the mechanism of lenvatinib's antitumor efficacy through exhausted CD8⁺ T cells in HCC treatment.