破骨细胞分化在颞下颌关节骨关节炎发生中的作用

目的 探究破骨细胞分化在颞下颌关节骨关节炎(TMJOA)发生中的作用.方法 构建小鼠TMJOA模型,Micro-CT观察TMJOA发生发展过程中髁突骨质变化,苏木素伊红(HE)染色观察TMJOA关节组织学结构变化,抗酒石酸酸性磷酸酶(TRAP)组织染色观察TMJOA关节组织中破骨细胞的存在情况.收集TMJOA患者滑液,...     

A Unique Robust Dual-Promoter-Driven and Dual-Reporter-Expressing SARS-CoV-2 Replicon: Construction and Characterization

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, SARS2) remains a great global health threat and demands identification of more effective and SARS2-targeted antiviral drugs, even with successful development of anti-SARS2 vaccines. Viral replicons have proven to be a rapid, safe, and readily scalable platform for high-throughput screening, identification, and evaluation of antiviral drugs against positive-stranded RNA viruses. In the study, we report a unique robust HIV long terminal repeat (LTR)/T7 dual-promoter-driven and dual-reporter firefly luciferase (fLuc) and green fluorescent protein (GFP)-expressing SARS2 replicon. The genomic organization of the replicon was designed with quite a few features that were to ensure the replication fidelity of the replicon, to maximize the expression of the full-length replicon, and to offer the monitoring flexibility of the replicon replication. We showed the success of the construction of the replicon and expression of reporter genes fLuc and GFP and SARS structural N from the replicon DNA or the RNA that was in vitro transcribed from the replicon DNA. We also showed detection of the negative-stranded genomic RNA (gRNA) and subgenomic RNA (sgRNA) intermediates, a hallmark of replication of positive-stranded RNA viruses from the replicon. Lastly, we showed that expression of the reporter genes, N gene, gRNA, and sgRNA from the replicon was sensitive to inhibition by Remdesivir. Taken together, our results support use of the replicon for identification of anti-SARS2 drugs and development of new anti-SARS strategies targeted at the step of virus replication.     

箭叶橐吾中萜类成分的研究

目的：研究民间草药箭叶橐吾根及根茎的化学成分。方法：乙醇总提物经反复硅胶柱色谱,Sephadex LH-20柱色谱纯化,根据理化性质和光谱数据鉴定化合物结构。结果：分离鉴定了7个萜类化合物,其中5个为倍半萜类,7α-hydroxy-9(10)-ene-1,8-dioxo-6,7-dihydrofuranoeremophilane(1),1β,10β-epoxy-6β,8β-dihydroxy-eremophil-7(11)-en-12,8α-olide(2),1-oxo-9-desoxycacalol(3),benzofuranoeremophil-1-ene(4),蜂斗菜内酯A(bakkenolide A)(5)；2个为三萜类化合物,3β,16β-dihydroxy-12-oleanen-28-al(6)和羽扇醇(lupeol)(7)。结论：化合物1～3和6为首次从箭叶橐吾中分离得到,其中化合物3和6为橐吾属内首次报道。     

N-三甲基壳聚糖对睾酮凝胶在兔体内药动学的作用研究

 目的研究N-三甲基壳聚糖(N-trimethyl chitosan,TMC)对睾酮凝胶在兔体内药动学的作用,考察TMC的透皮吸收促进作用效果。方法用壳聚糖及碘甲烷为主要原料,合成季铵化程度分别为40%和60%的TMC,即TMC40和TMC60,通过¹H-NMR确定其季铵化程度。以泊洛沙姆P407为基质制备4份凝胶,以睾酮为模型药物,以月桂氮酮(2%)为阳性对照,以不加促渗剂为阴性对照,另两份凝胶分别含TMC40和TMC60各5%作为促渗剂。经皮给药后采用RP-HPLC测定兔血浆中的睾酮浓度,计算药动学参数,对4种凝胶进行比较,考察TMC40,TMC60的促渗效果。结果经1H-NMR确定合成得到的TMC40,TMC60季铵化程度分别为38.8%和67.2%。主要药动学参数t_max,ρ_max,K_a,AUC经方差分析及双单侧t检验后,TMC60较空白组及月桂氮酮组各参数均具有显著性差异(P<0.05),TMC40较空白组有明显促进作用(P<0.05),较月桂氮酮组除参数K_a外无显著性差异(P>0.05)。结论TMC60具有显著的促进睾酮凝胶透皮吸收作用,TMC40较空白组促进吸收作用明显,但效果与2%月桂氮酮相比无显著性差异。     

阿勒泰橐吾的倍半萜类成分研究

 目的对菊科橐吾属植物阿勒泰橐吾(Ligularia altaica DC.)的萜类成分进行研究并进行抗白血病细胞K₅₆₂的活性筛选。方法采用硅胶、凝胶柱色谱和重结晶等技术进行分离纯化,根据理化性质和波谱数据并参考文献确定化合物结构,采用MTT法进行抗K562细胞增殖的活性筛选。结果分离鉴定了9个倍半萜化合物:furaneremophilan-14β,6α-olide(1),8β-hydroxyl-7(11)-eremophilen-12,8α-olide(2),7(11)-eremophilen-12,8α-olide(3),8β-hydroxyl-eremophil-7(11)-en-12,8α(14β,6α)-diolide(4),6β-hydroxyl-7(11)-eremophilen-12,8α-olide(5),6β,8β-dihydroxyl-7(11)-en-12β,8α-olide(6),7-acetyl-6(7)-en-noreremophil-13β-carboxylic acid(7),8β-hydroeremophil-7(11)-eremophilen-12,8α(14β,6α)-diolide(8)和2-hydroxyl-plary phillide(9)。结论以上化合物均为首次从该种植物中分离得到,eremophilane型降倍半萜化合物7和9对K₅₆₂细胞生长显示弱的抑制活性。     

p27kip1蛋白在卵巢上皮癌中的表达及其临床意义

目的 :研究p2 7kip1在卵巢上皮癌中的表达及其临床意义。方法 :采用免疫组化SP法检测 2 0例卵巢良性、5 8例卵巢恶性上皮性肿瘤中p2 7kip1蛋白的表达。应用Kaplan Meier法及Cox比例风险回归模型 ,分析p2 7kip1蛋白表达与卵巢上皮癌患者预后的关系。结果 :(1)卵巢良性和恶性上皮性肿瘤中p2 7kip1蛋白表达阳性率分别为75 .0 % ,4 6 .6 % ,恶性肿瘤中p2 7kip1蛋白表达阳性率明显低于良性肿瘤 ,恶性肿瘤染色阳性部位以胞浆为主 ;(2 )p2 7kip1蛋白的表达与病理学分级有关 ,与年龄、临床分期、淋巴结转移、组织学亚型无关 ;(3)卵巢上皮癌中 ,p2 7kip1蛋白的表达与bax蛋白的表达呈正相关 ,与bcl 2蛋白的表达呈负相关 ,与ki6 7蛋白无明显相关性 ;(4)p2 7kip1蛋白表达是影响卵巢上皮癌患者预后的独立因素 ,阳性者预后较好。结论 :p2 7kip1蛋白可能与卵巢上皮癌的发生有关。p2 7kip1蛋白可作为判断患者预后的指标。     

N-三甲基壳聚糖对环孢素经皮渗透作用的试验研究

OBJECTIVE To study the penetration effect of N-trimethyl chitosan(TMC) on Cyclosporin.METHODS TMC60 was synthesized by a two-step method using chitosan and methyl-iodide.The degree of quaternization(DQ) of TMC was determined by 1H-NMR.The excised mice ski     

复方甘草酸苷胶囊的人体生物等效性研究

目的 评价复方甘草酸苷胶囊在健康人体中的生物等效性.方法 采用LC-MS法测定人血浆中的甘草次酸;用随机双交叉自身对照试验设计,24名受试者分别口服75 mg受试制剂和参比制剂后,测定甘草酸苷代谢物甘草次酸的血药浓度,计算药物动力学参数,评价两制剂的生物等效性.结果 复方甘草酸苷胶囊和片剂中甘草次酸的t1/2分别为9....     

中药虎杖商品药材的定性鉴别与定量分析

目的建立较为合理的中药虎杖的质量评价标准.方法化学定性鉴别采用TLC法,含量测定采用HPLC法.结果以白藜芦醇苷和大黄素为对照品,以不同的展开系统展开,建立了虎杖的TLC定性鉴别方法;以白藜芦醇苷为对照品建立了HPLC含量测定方法.结论建立的TLC方法对虎杖药材的鉴别具有较好的专属性,能够区别虎杖与同科属常用药材(2000年版中国药典收载的同科根与根茎类药材).本文建立的测定白藜芦醇苷含量的HPLC法简单、准确,重现性好.