六味地黄丸治疗围绝经期综合征的临床研究进展

围绝经期综合征是女性绝经前后的常见疾病,临床研究发现六味地黄丸治疗该病具有较好的疗效。经典名方六味地黄丸由熟地黄、山茱萸、山药、泽泻、牡丹皮、茯苓6味中药组方,可有效改善患者的血管舒缩、情绪失常、睡眠障碍、脂代谢紊乱、骨质流失等症状,其药效机制可能在于调节患者的雌激素水平,进而改善患者全身症状。综述六味地黄丸治疗围绝经期综合征的临床研究进展,以期为后续临床和实验研究提供参考。     

青钱柳多糖对H4IIE肝细胞胰岛素信号传递的影响

目的：观察青钱柳多糖对肝细胞胰岛素信号传导通路关键靶点基因、蛋白表达的影响。方法：以H4IIE大鼠肝细胞为模型,培养72h后,采用Neutral Red法检测青钱柳多糖（50、100、200、400μg·mL^-1）对细胞活性的影响;根据细胞活性检测结果分为正常对照组（Control组）、胰岛素组（Insulin组）、青钱柳多糖低剂量组（LCP组）和高剂量组（HCP组）;药物干预2h后RT-PCR检测肝细胞相应基因表达,药物干预30min后,利用Western blot法检测肝细胞相应蛋白磷酸化水平。结果：与Control组比较,100、200、400μg·mL^-1青钱柳多糖干预后肝细胞活性显著升高（P<0.01）;干预2h 后,LCP组InsR、IRS-2基因表达显著升高（P<0.05）,Insulin组和HCP组InsR、IRS-2基因表达极显著升高（P<0.01）;干预30min后,Insulin组、HCP组InsR β、IRS-2、Akt蛋白磷酸化水平显著升高（P<0.01）。结论：青钱柳多糖具有增加肝细胞活性作用,其上调肝细胞胰岛素信号通路关键靶点InsR、IRS-2基因表达,以及InsR β、IRS-2、Akt蛋白磷酸化水平可能是其发挥降糖作用的机制。     

小叶黑柴胡药材的HPLC指纹图谱研究

目的建立小叶黑柴胡药材的HPLC指纹图谱。方法以Kromasil C18为色谱柱,流动相为乙腈-水梯度洗脱,体积流量1.0 mL/min,检测波长260 nm。结果建立了小叶黑柴胡药材的HPLC指纹图谱,确定了14个共有峰,共有峰相对保留时间的RSD为0.02%~1.49%,相对峰面积的RSD为6.12%~58.75%,10批样品的相似度均大于0.9。结论本方法简单可靠,可用于小叶黑柴胡药材的质量控制。     

《中医方剂大辞典》中含栀子方剂用药规律分析

栀子为药食两用的物品,不仅在中医临床中经常使用,在食品与保健食品中也应用广泛。《中医方剂大辞典》是中医方剂的集大成者,为方剂与中药的开发研究提供了良好素材。该文基于中医传承辅助平台(TCMISS),分析《中医方剂大辞典》中含栀子方剂组方规律,为栀子的临床应用及深度研发提供参考。应用TCMISS将含栀子方剂构建数据库,使用该软件的频次统计、关联规则等数据处理方法,分析含栀子方剂中的常用药物、组合规律、核心组合。共纳入方剂3 523首,涉及中药1 725味,设支持度352(10%)、置信度90%,共得到在含栀子方剂中出现频次较高的药物组合57对,核心组合用药较为集中,组方法度清晰;主治疾病18种。其中,栀子常与清热解毒、祛风解表、活血行气、活血化瘀之品联用,主以黄疸、伤寒、头痛等为治疗病症。     

羟基和甲氧基取代苯甲醛在亚硫酸氢钠-乙酸乙酯-水两相中分配系数的测定

 目的 以羟基和甲氧基取代的4个苯甲醛系列化合物为对象,测定它们在亚硫酸氢钠-乙酸乙酯-水两相体系中的分配系数,采用亚硫酸氢钠加成和盐酸酸化的方法研究提取和分离天然醛类化合物的可行性。方法 采用亚硫酸氢钠加成反应,将脂溶性的醛类化合物转化成水溶性的α-羟基磺酸钠衍生物,使醛类化合物从有机相转移到水相。采用高效液相色谱法测定不同比例的亚硫酸氢钠-乙酸乙酯-水两相体系中这些化合物在上相与下相之间的分配系数。采用盐酸酸化和分配萃取,实现α-羟基磺酸钠衍生物还原为原有的醛类化合物。结果 醛类化合物的分配系数,随着亚硫酸氢钠-乙酸乙酯-水两相体系中亚硫酸氢钠比例的增加急剧减小,并达到平衡。结论 通过亚硫酸氢钠加成反应和盐酸酸化,使脂溶性的醛类化合物经水溶性的α-羟基磺酸钠衍生物还原到原始的醛类化合物,经两次萃取,可以实现天然产物中醛类化合物专属性的提取和分离。     

Efficacy and safety of transcatheter arterial chemoembolization-lenvatinib sequential therapy for patients with unresectable hepatocellular carcinoma: a single-arm clinical study

BackgroundRepeated transcatheter arterial chemoembolization (TACE) could cause ischemia of the tumor tissue and increases production of angiogenic factors in patients with hepatocellular carcinoma (HCC). Lenvatinib can inhibit the expression of angiogenic factors induced by ischemia after TACE and reduce angiogenesis and tumor recurrence. TACE-lenvatinib sequential therapy may improve clinical outcomes. There have been few investigations of TACE-lenvatinib sequential therapy for the treatment of unresectable HCC. We aimed to evaluate the efficacy and safety of TACE-lenvatinib sequential therapy for unresectable HCC.MethodsFrom May 2018 to May 2021, 53 consecutive patients who underwent TACE-lenvatinib sequential therapy were retrospectively reviewed. Of these, 30 patients who met the inclusion criteria were selected. Lenvatinib treatment started within 1 or 2 weeks after TACE at a dose of 8 or 12 mg once daily. Treatment response was assessed using dynamic magnetic resonance imaging (MRI) according to the modified response evaluation criteria in solid tumor (mRECIST). Blood tests were also performed at every response evaluation. Patients with complete response (CR) or partial response (PR) and stable disease (SD) received continuous lenvatinib therapy, and patients with progressive disease (PD) received repeated TACE. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were calculated. Statistical analysis was performed using the Kaplan-Meier method.ResultsThe median age was 58.5±9.1 years, and 16.7% (5/30) of patients were female. A total of 12 patients were categorized as Barcelona Clinic Liver Cancer (BCLC) Stage B and 18 were BCLC Stage C. The mean follow-up time was 15.7 months. The ORR was 76.7% (23/30), and the DCR was 96.7% (29/30). The median PFS was 6.1 months, and the median OS was 20.7 months. The most common lenvatinib-related AE was rash, and the most common TACE-related AE was elevated aspartate aminotransferase (AST). No treatment-related mortality was observed.ConclusionsFrom our findings, TACE-lenvatinib sequential therapy may prolong OS and PFS in patients with unresectable HCC, and the side effects are acceptable. The efficacy and safety of the sequential therapy should be confirmed in multiple center randomized controlled trials (RCTs) with a large sample and sufficient follow-up period.     

基于斑马鱼模型比较宽体金线蛭和菲牛蛭对血管新生的影响

摘 要 目的：探讨及比较宽体金线蛭和菲牛蛭对Tg（kdrl:mCherry）斑马鱼的血管新生影响。方法: 将受精后 6 ~ 8 h（6 ~ 8hpf）的胚胎暴露在含不同浓度宽体金线蛭和菲牛蛭水提取物的胚胎培养液中,每24 h更换一次含药培养液。72 hpf时,在显微镜下观察发育形态和节间血管,测定48,72 hpf孵化率,72 hpf节间血管数目、心率。结果: 在抑制血管新生方面,宽体金线蛭组浓度≥30 μg· ml^-1时,菲牛蛭组浓度≥20 μg· ml^-1时,斑马鱼节间血管数目均较空白组明显减少（P<0.01）。毒性方面,在48 hpf,给药组浓度≥40 μg· ml^-1时,宽体金线蛭和菲牛蛭组斑马鱼的孵化率均较空白组明显降低（P<0.01）;在72 hpf,宽体金线蛭组斑马鱼的孵化率在100 μg·ml^-1时较空白组明显降低（P<0.01）,而菲牛蛭组斑马鱼的孵化率在80 μg· ml^-1就明显降低（P<0.01）。宽体金线蛭和菲牛蛭组斑马鱼的卵黄囊、心囊无明显水肿,脊柱未弯曲;两组心率显著降低（P<0.01）,但在正常心率范围内。结论: 宽体金线蛭和菲牛蛭都具有抗血管生成活性,且菲牛蛭的抗血管生成活性强于宽体金线蛭。两者对斑马鱼发育有一定程度的影响,但毒性不大。     

The latest review on the polyphenols and their bioactivities of Chinese Morus plants

The mulberry tree (Morus alba) plays a key role in agriculture, and its different parts have been used as popular Traditional Chinese Medicines for thousands of years. There are 16 species belonging to the Morus genus. Among them, 11 species distribute in China, most of which have been used as the substitutes of M. alba in local provinces. This review summarizes the structural characters of polyphenols, the main components in Morus, including Diels–Alder-type adducts, flavonoids, 2-arylbenzofurans, and stilbenes, and also their related bioactivities in the last 10 years.     

二萜合酶的研究进展

植物二萜类化合物广泛存在于自然界中,是一类重要的天然化合物。随着一些具有重要经济价值的二萜不断被发现,其生物合成中的二萜合酶也倍受关注。二萜合酶催化活性的多样性决定了终产物(二萜化合物)的丰富性。本文重点探讨了近年来二萜生物合成途径和二萜合酶的类型、克隆、催化机制及其合成生物学应用等研究进展。     

基于模糊层次分析法优选红花通络方最佳提取工艺路线

目的构建多层次指标评价模型以优选红花通络方(HTP)最佳提取工艺路线。方法选取有效成分、杂质控制、行为学、组织病理学、免疫监测作为准则层,方中代表性成分羟基红花黄色素A、淫羊藿苷的提取率,出膏率,大鼠机械性刺激痛觉超敏反应、机械性刺激痛觉过敏反应的缩足百分率,背根神经节细胞偏心核比率,足底P物质量作为指标层,运用模糊层次分析法(FAHP)为各指标赋权,综合评价HTP各提取工艺路线。结果准则层指标权重(ω)由高到低为免疫监测(ω=0.245)、组织病理学(ω=0.23)、有效成分和行为学(ω=0.20)、杂质控制(ω=0.125)。最佳工艺路线为红花60℃温浸、淫羊藿等水回流提取、桂枝80%乙醇回流提取。结论以FAHP为赋权方法,有效成分指标结合药效学指标和杂质控制作为评价指标来优选提取工艺路线的方法,既能保留复方有效合理的本质,又能满足现代制剂研发的要求。