Lyophilization provides long-term stability for a lipid nanoparticle-formulated,nucleoside-modified mRNA vaccine

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A Multi-Targeting,Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice

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补肾调经汤对多囊卵巢综合征伴胰岛素抵抗肾虚痰阻证患者糖脂代谢和子宫内膜容受性的影响

目的观察自拟补肾调经汤对多囊卵巢综合征伴胰岛素抵抗肾虚痰阻证患者糖脂代谢和子宫内膜容受性的影响。方法将2018年1月—2019年2月山东省立医院收治的90例多囊卵巢综合征伴胰岛素抵抗肾虚痰阻证患者随机分为2组,对照组给予屈螺酮炔雌醇片、盐酸二甲双胍片口服,血脂异常者给予普伐他汀钠片口服,观察组在对照组治疗基础上给予补肾调经汤治疗,2组均连续治疗3个月经周期,对比2组治疗前后糖代谢指标[空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、脂代谢指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、子宫内膜容受性(子宫内膜厚度、子宫螺旋动脉搏动指数、子宫螺旋动脉阻力指数),评估2组临床疗效及不良反应发生情况。结果与治疗前比较,2组治疗后FPG、FINS、HOMA-IR、TC、TG、LDL-C水平及子宫螺旋动脉搏动指数、子宫螺旋动脉阻力指数均明显降低(P均<0.05),且观察组均明显低于对照组(P均<0.05);与治疗前比较,2组治疗后HDL-C、子宫内膜厚度均明显升高(P均<0.05),且观察组均明显高于对照组(P均<0.05)。观察组治疗总有效率为91.1%(41/45),明显高于对照组的71.1%(32/45),差异有统计学意义(χ²=5.874,P<0.05);2组治疗期间均未发生严重不良反应。结论补肾调经汤联合西药治疗多囊卵巢综合征伴胰岛素抵抗肾虚痰阻证患者效果更好,能够有效调节糖、脂代谢,改善子宫内膜容受性,且安全。     

腹部推拿对高脂饮食诱发肥胖大鼠胰岛素抵抗的改善作用机制

目的:观察腹部推拿对肥胖大鼠胰岛素抵抗的改善作用与机制。方法:将60只大鼠随机分为空白对照组和模型组,空白对照组喂养普通饲料;模型组喂养高脂饲料造模,造模成功大鼠随机分为模型对照组和推拿干预组。两组均继续采用高脂饲料喂养,推拿干预组采用腹部推拿疗法进行干预。4周后观察各组动物空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)、骨骼肌单磷酸腺苷活化蛋白激酶(AMPK)、沉默信息调节因子(SIRT1)、过氧化物酶体增生物激活受体Y共活化因子lα(PGC-1α)蛋白表达水平。结果:模型对照组的FPG与TC、LDL-C、FINS、HOMA-IR均显著高于空白对照组(P<0.05,P<0.01),TG、HDL-C、ISI及骨骼肌AMPK、PGC-1α、SIRT1蛋白表达水平均显著低于空白对照组(P<0.01);推拿干预组与模型对照组比较,FPG、TC、LDL-C、FINS、HOMA-IR均显著降低(P<0.05,P<0.01),TG、HDL-C、ISI及骨骼肌AMPK、SIRT1、PGC-1α蛋白表达水平均显著升高(P<0.05,P<0.01)。结论:腹部推拿疗法能够有效调节肥胖大鼠的胰岛素抵抗现象,其可能的机制之一是改善和加强了骨骼肌SIRT1/PGC-lα通路的作用,更好发挥其调节糖脂代谢及胰岛素分泌的功能。     

肿瘤坏死因子可致机体脂质过氧化损伤

采用ＳＤ大鼠持续泵入人工重组肿瘤坏死因子。型（ｒｈ－ＴＮＦ－ａ），以６×１０￣５Ｕ·ｋｇ￣－１／ｄ速度作用７２ｈ，观察血浆及组织丙二醛（ＭＤＡ）含量，全血和组织超氧化物歧化酶（ＳＯＤ）活性，组织超弱发光和白细胞吞噬发光的变化。结果：血浆及组织ＭＤＡ含量明显增加，全血ＳＯＤ活性显著下降，组织ＳＯＤ活性所受影响较小，肾、肠组织超弱发光明显增强，白细胞吞噬发光无明显变化。实验表明：持续７２ｈ泵入ＴＮＦ作用于大鼠，可使机体自由基产生增加，自由基清除系统部分受损，而导致脂质过氧化损伤，但对分叶核粒细胞的呼吸爆发作用无明显影响。     

苦参碱固体脂质纳米粒的制备及其体外透皮研究

目的制备苦参碱固体脂质纳米粒(matrine solid lipid nanoparticles,MA-SLN),并考察其药剂学性质与体外透皮给药行为。方法采用微乳-低温固化法制备MA-SLN,以粒径、ζ电位和包封率为评价指标,通过正交试验筛选最佳处方和工艺;扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察MA-SLN的形态;差示扫描量热法(DSC)和X射线衍射扫描(XRD)分析苦参碱在MA-SLN中的包埋状态;体外透皮实验考察药物的透皮及释放行为。结果最佳处方工艺制得的MA-SLN包封率可达(56.12±0.82)%,激光粒度仪(DLS)检测MA-SLN的平均粒径为(196.31±6.26)nm,电位为(-37.18±2.36)mV。SEM和TEM显示MA-SLN呈规整的均匀球状或类球状结构;DSC和XRD检测可确定苦参碱可完全包裹在SLN内,苦参碱与SLN骨架材料相容性良好;体外透皮实验显示,9 h时累积透过量(ΔM)达到500μg/cm~2,且可持续释放至24 h,表明MA-SLN能够显著提高苦参碱的透皮吸收效率并具有较好的缓释行为。结论采用微乳-低温固化法制备MA-SLN,其工艺简单、周期短、可控性高,易于产业化推广;且制成的MA-SLN性能优良、透皮吸收率高与缓释行为显著,可为透皮给药制剂提供一种较好的给药模型,为苦参碱进一步开发应用奠定基础。     

熊果酸磷脂复合物纳米结构脂质载体的制备及其体内药动学研究

目的制备熊果酸磷脂复合物纳米结构脂质载体,并考察其体内药动学。方法乳化?超声分散法制备熊果酸磷脂复合物纳米结构脂质载体,测定粒径、Zeta电位、包封率、载药量、体外释药。大鼠灌胃给药(12.5 mg/mL)后,于0.25、0.75、1、1.5、2、2.5、3、4、6、8、12 h采血,HPLC法测定熊果酸血药浓度,计算主要药动学参数。结果所得制剂呈类球形或球形,平均粒径、Zeta电位、包封率、载药量分别为(209.32±4.47)nm、-(10.82±0.42)mV、80.54%、3.57%;36 h内累积释放度低于70%,释药符合Weibull模型(R2=0.9906)。与原料药、磷脂复合物比较,纳米结构脂质载体tmax延长(P<0.05,P<0.01),Cmax、AUC0~t、AUC0~∞升高(P<0.01);与原料药比较,磷脂复合物、纳米结构脂质载体相对生物利用度分别增加至2.73、3.95倍。结论磷脂复合物纳米结构脂质载体可促进熊果酸体内吸收,提高其口服生物利用度。     

加味参红宁心方对经皮冠状动脉介入治疗术后再狭窄患者血脂、超敏C反应蛋白的影响研究

目的观察加味参红宁心方联合西药对冠心病经皮冠状动脉介入治疗(PCI)术后再狭窄患者血清超敏C反应蛋白(hs-CRP)和血脂的影响。方法选取PCI术后再狭窄患者60例,随机分为观察组和对照组,各30例。对照组给予氯吡格雷片75 mg,阿司匹林片100 mg,阿托伐他汀钙片(立普妥)20 mg,均每日1次,口服。观察组在此基础上加用加味参红宁心方。2组治疗均为12周,观察2组hs-CRP和血脂水平。结果 2组hs-CRP 水平较治疗前明显下降,观察组下降更为明显(P<0.05);2组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均较治疗前下降(P<0.05);其中TC、LDL-C 观察组较对照组下降更为明显(P<0.05)。结论加味参红宁心方联合西药能较好地降低PCI术后再狭窄患者的血脂,抑制炎症反应。     

Proteomic analysis of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention

ObjectiveTo investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.MethodsSeventy-one subjects were enrolled in the study. We assessed blood glucose, blood lipids, body mass index (BMI), and phlegm-dampness pattern, which was confirmed by a traditional Chinese medicine clinician. Of the participants, we included healthy participants with normal weight (NW, n = 23), overweight/obese participants with normal metabolism (ONM, n = 19), overweight/obese participants with pre-diabetes (OPD, n = 12), and overweight/obese participants with marginally-elevated blood lipids (OML, n = 17). Among them, the ONM, OPD, and OML groups were diagnosed with phlegm-dampness pattern. The data-independent acquisition (DIA) method was first used to analyze the plasma protein expression of each group, and the relevant differential proteins of each group were screened. The co-expressed proteins were evaluated by Venn analysis. The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis (IPA) software. Parallel reaction monitoring (PRM) was used to verify the differential and common proteins in each group.ResultsAfter comparing ONM, OPD, and OML groups with NW group, we identified the differentially expressed proteins (DEPs). Next, we determined the DEPs among OPD, OML, and ONM groups. Using Venn analysis of the DEPs in each group, 24 co-expressed proteins were screened. Two co-expressed proteins were verified by PRM. IPA analysis showed that pathways including LXR/RXR activation, acute phase response signaling, and FXR/RXR activation were common to all three groups of phlegm-damp overweight/obesity participants. However, the activation or inhibition of these pathways was different among the three groups.ConclusionParticipants with overweight/obesity have similar proteomic characteristics, though each type shows specific proteomic characteristics. Two co-expressed proteins, VTN and ORM1, are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegm-dampness retention.