Cytotoxic Mechanisms of FK317, a New Class of Bioreductive Agent with Potent Antitumor Activity

FK317 is a member of a new class of bioreductive agents that exhibit strong cytotoxicity against various human cancer cells. The effect of FK317 was found to be stronger than that of mitomycin C (MMC), adriamycin (ADR) or cisplatin (CDDP). Alkaline elution analysis indicated that FK317 formed interstrand DNA-DNA and DNA-protein cross-links in cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK317. In a cell-free system the deacetylated metabolites produced cross-linked DNA under reductive conditions, though FK317 itself did not form DNA-DNA cross-links. In order to elucidate the metabolic activation mechanisms, we established an FK317-resistant subline from human non-small cell lung cancer cells (Lu99) by stepwise and brief exposure (1 h) to FK317. The resistant subline (Lu99/317) showed cross-resistance to MMC and carboquone (CQ), but not to ADR or CDDP. DT-diaphorase, which is one of the activation enzymes of MMC and CQ, was deficient in Lu99/317 cells as determined by enzyme activity assay. However, the levels of NADPH:cytochrome P450 reductase, which is another activation enzyme for MMC and CQ, were comparable in resistant and parent cell lines. Treatment of the cells with dicumarol, an inhibitor of DT-diaphorase, reduced the cytotoxicity of FK317 to Lu99 cells, but not to Lu99/317 cells. These results indicate that deacetylation of FK317 is necessary for its reductive activation, and deacetylated FK317 is reduced by DT-diaphorase to form an active metabolite, which produces DNA-DNA interstrand and DNA-protein cross-links that lead to cell death.     

Halichondria属软海绵次生代谢产物及其生物活性

Halichondria属软海绵分布广泛,含多种生物活性成分,引起人们的深入研究。近30年来,已从Halichon-dria属软海绵中分离得到了许多结构新颖,有抗菌、抗肿瘤和抗病毒等生物活性的次生代谢产物,如大环内酯、聚醚、生物碱、内酰胺、萜类、甾醇、鞘类脂糖苷等。在调研国内外相关资料的基础上,按化合物的结构类型简要介绍了1978—2003年Halichondria属软海绵次生代谢产物及其生物活性的研究概况,为进一步的研究工作提供参考。     

结扎橡皮圈应力松弛的研究

目的通过定期测量结扎橡皮圈负载后应力的变化，研究它应力松弛的过程及在不同负载下应力松弛率的异同。方法选取结扎橡皮圈30个，随机分为3组，每组10个，3组试样分别负载100g、150g和200g。通过定期测量结扎橡皮圈在不同负载下的应力，了解应力的变化过程。对3组试样的应力变化进行统计分析。结果结扎橡皮圈在最初的48h内应力衰减较快，负载48h后残余应力为初始应力的80％左右（78．4％-83．5％），之后应力松弛的速率逐渐减小，至第32天时残余应力为初始应力的73．1％-85．8％。结论结扎橡皮圈在不同负载下均存存应力松弛的现象，应力松弛率相同。     

益气通腑汤治疗女性直肠前突随机平行对照研究

[目的]观察益气通腑汤治疗女性直肠前突疗效。[方法]使用随机平行对照方法,将123例随机分为两组,对照组60例麻仁丸口服,治疗组60例益气通腑汤化裁。3个月为1疗程,治疗1疗程(90d)判定疗效。[结果]治疗组临床治愈6例,有效40例,无效14例,总有效率76.67%。对照组临床治愈1例,有效21例,无效38例,总有效率36.67%。治疗组疗效优于对照组(P<0.01)。[结论]中医药以整体观念为原则,以调理脏腑机能为根本,弥补了西医治疗的不足,值得临床推广。     

导乐陪伴配合音乐放松对分娩影响的临床观察

[目的]探讨导乐陪伴配合音乐放松对分娩的影响。[方法]选择愿意阴道分娩的孕妇142例,随机分为实验组和对照组,实验组分娩时指派1名助产士在孕妇自己挑选的音乐背景下指导孕妇配合分娩;对照组孕妇产程发动后指派1名助产士陪伴分娩。[结果]实验组产妇的产前焦虑评分、宫口开大3cm和10cm的疼痛评分、产程进展情况、剖宫产率、难产率、产后出血量与对照组有显著差别。[结论]导乐陪伴配合音乐放松,可以减轻分娩前的焦虑、分娩时的疼痛和加快产程进展,降低剖宫产率、难产率和产后出血量,对新生儿评分无明显影响。导乐陪伴配合音乐放松对分娩是人性化服务,有利于提高产科质量。     

Gd/Mn Co-Doped CaBi4Ti4O15 Aurivillius-Phase Ceramics: Structures,Electrical Conduction and Dielectric Relaxation Behaviors

In this work, Gd/Mn co-doped CaBi₄Ti₄O₁₅ Aurivillius-type ceramics with the formula of Ca_1-xGd_xBi₄Ti₄O₁₅ + xGd/0.2wt%MnCO₃ (abbreviated as CBT-xGd/0.2Mn) were prepared by the conventional solid-state reaction route. Firstly, the prepared ceramics were identified as the single CaBi₄Ti₄O₁₅ phase with orthorhombic symmetry and the change in lattice parameters detected from the Rietveld XRD refinement demonstrated that Gd³⁺ was successfully substituted for Ca²⁺ at the A-site. SEM observations further revealed that all samples were composed of the randomly orientated plate-like grains, and the corresponding average grain size gradually decreased with Gd content (x) increasing. For all compositions studied, the frequency independence of conductivity observed above 400 °C showed a nature of ionic conduction behavior, which was predominated by the long-range migration of oxygen vacancies. Based on the correlated barrier hopping (CBH) model, the maximum barrier height W_M, the dc conduction activation energy E_dc, as well as the hopping conduction activation energy E_p were calculated for the CBT-xGd/0.2Mn ceramics. The composition with x = 0.06 was found to have the highest E_dc value of 1.87 eV, as well as the lowest conductivity (1.8 × 10⁻⁵ S/m at 600 °C) among these compositions. The electrical modules analysis for this composition further illustrated the degree of interaction between charge carrier β increases, with an increase in temperature from 500 °C to 600 °C, and then a turn to decrease when the temperature exceeded 600 °C. The value of β reached a maximum of 0.967 at 600 °C, indicating that the dielectric relaxation behavior at this temperature was closer to the ideal Debye type.     

基于盆底肌加强的阴道紧缩术

目的 探讨通过加强盆底相关肌群在提升阴道紧缩术临床效果中的作用及其关键操作.方法:从作者手术项目组2018年1月至2019年12月期间实施的盆底肌加强型阴道紧缩术案例中,随机选择50例作为观察对象.均采用阴道粘膜和会阴皮肤菱形切口,行粘膜下潜行分离,依次暴露会阴浅横肌、球海绵体肌和双侧肛提肌;首先拉拢缝合固定肛提肌;然...     

基于UFLC-IT-TOF-MS技术的牡荆子中2个木脂素在大鼠体内代谢研究

目的对牡荆子中2个木脂素单体化合物6-羟基-4-(4-羟基-3-甲氧基苯基)-3-羟甲基-7-甲氧基-3,4-二氢-2-萘醛(VB-1)和vitedoin A(VB-2)在大鼠体内的代谢情况进行研究。方法采用超快速液相色谱-离子阱飞行时间质谱(UFLC-IT-TOF-MS)技术,鉴定大鼠分别ig给予2个木脂素单体化合物后,粪便、尿液、胆汁、血浆中的代谢产物。结果发现并确证了2个木脂素原型及其11个代谢产物在大鼠体内的存在。通过代谢产物鉴定分析了其主要代谢途径,发现在大鼠体内这2个木脂素成分发生了葡萄糖醛酸化、硫酸化、羟化、羟化硫酸化、还原葡萄糖醛酸化和还原硫酸化等代谢反应。结论通过对2个木脂素单体化合物代谢产物的分析,基本阐明了其在体内的代谢过程,为进一步的药理活性及其机制研究提供了依据。     

松脂醇二葡萄糖苷大鼠胆汁内排泄研究

[目的]建立液质联用方法,同时测定胆汁中松脂醇二葡萄糖苷和其代谢产物松脂醇单葡萄糖苷的含量,研究两者在胆汁内排泄特征。[方法]大鼠灌胃给药松脂醇二葡萄糖苷的生理盐水溶液,并按照设定的时间点收集胆汁。以华法林单体为内标,建立液质联用分析方法,测定灌胃给药后大鼠胆汁中松脂醇二葡萄糖苷和其代谢产物松脂醇单葡萄糖苷的含量变化情况。[结果]松脂醇二葡萄糖苷和松脂醇单葡萄糖苷在8~5 000 ng/m L范围内线性关系良好,日内精密度和日间精密度及其他方法学考察项RSD均符合生物样本定量要求。给药后松脂醇二葡萄糖苷和松脂醇单葡萄糖苷的累积排泄量在给药之后不断增长,到6 h后保持一个平稳状态;排泄速率在4 h时到达顶峰,之后迅速降低,6 h后保持一个较低的状态,实验后期大鼠排泄率有上升趋势。[结论]该方法符合生物样品检测要求,可用于松脂醇二葡萄糖苷和松脂醇单葡萄糖苷的同时定量测量。     

17-氢-9-去氢穿心莲内酯体外代谢速率及代谢产物研究

应用体外大鼠肝微粒体孵育体系,研究喜炎平注射液中主要有效成分17-氢-9-去氢穿心莲内酯(DHA)的体外代谢速率及代谢产物。将17-氢-9-去氢穿心莲内酯与加入NADPH的大鼠肝微粒体共同孵育,采用超高效液相色谱-三重四极杆串联质谱法(UHPLC-MS/MS)测定其剩余浓度,考察17-氢-9-去氢穿心莲内酯的肝微粒体代谢速率,并采用超高效液相色谱串联飞行时间质谱(UPLC-TOF-MS^E)对孵育体系中17-氢-9-去氢穿心莲内酯的代谢产物进行鉴定。研究结果显示在加入辅酶的大鼠肝微粒体中,17-氢-9-去氢穿心莲内酯代谢速率较快,其半衰期(t_1/2)和肝微粒体中清除率(CL)分别为(19.7±0.5) min和(35.1±0.8) mL·min^-1·g^-1。高分辨质谱数据结合文献信息共鉴定孵育体系中17-氢-9-去氢穿心莲内酯的9个代谢产物,主要为羟基化产物和脱氢产物。鉴定结果为筛选出活性更好的穿心莲二萜内酯类衍生物提供了一定的依据。