基于生物信息学的乳腺癌关键基因筛选及实验验证

目的:通过利用生物信息学技术,筛选乳腺细胞癌组织与正常组织间的差异表达基因,明确其潜在治疗药物,为将来临床乳腺癌的免疫靶向治疗及药物治疗提供参考。方法:利用基因表达数据库(gene expression omnibus,GEO)检索关键词“乳腺癌”,下载GSE79586芯片数据,通过生信技术筛选对照组及乳腺癌模型组差异表达基因并对其进行基因本体(GO)功能分析、京都基因与基因组百科全书(KEGG)分析、差异基因特征表达分析以及蛋白互作网络(PPI)分析,对分析结果进一步可视化处理。通过GEPIA、GeneMANIA、Timer2.0数据库分别进行预后分析、相关功能预测以及免疫浸润分析。最终通过Connectivity Map(CMap)明确对乳腺癌具有潜在治疗作用的化合物。采用蛋白质印迹法及实时荧光定量PCR(RT-PCR)对核心基因及相关性最高的潜在治疗药物吉非替尼进行体外验证。结果:共筛选到包括1786个上调基因和2130个下调基因在内的3916个差异表达基因;GO结果显示差异基因主要参与磷酸化的正向调节、分泌囊泡、外消旋酶和差向异构酶活性等功能;KEGG结果显示差异基因主要参与系统性红斑狼疮、酒精中毒、粘着斑、阿米巴痢疾等疾病通路与Ras信号通路等;差异基因特征表达分析显示MEK抑制剂、HSP90抑制剂以及信号转导通路激酶抑制剂等是与差异基因相似的药物;PPI结果显示H2AFJ、TFF1、GATA3、FOXA1、CDH1等是与乳腺癌相关的核心基因;进一步选取相关性最高的H2AFJ、TFF1两个核心基因进行GEPIA分析。分析结果显示,原发性乳腺癌细胞组织中H2AFJ与TFF1 mRNA表达显著高于正常组织,并且与原发性乳腺癌细胞患者的病理分期、总生存率以及无病生存率存在显著相关性(P<0.01);H2AFJ与TFF1可能是影响乳腺癌细胞患者生存的潜在预后生物标志物;差异表达的H2AFJ与TFF1功能主要分别与激素受体结合、上皮结构维持和基因表观遗传负调控、参与转录负调控的染色质组织等过程有关;免疫浸润结果显示,H2AFJ与TFF1的表达与巨噬细胞、中性粒细胞、单核细胞、CD4^(+)T、CD8^(+)T以及B淋巴细胞等免疫细胞的浸润存在着显著相关性;CMap结果显示吉非替尼、阿培利西、索拉菲尼、舒尼替尼等化合物对乳腺癌具有潜在的治疗作用。Western blot和RT-PCR结果显示,H2AFJ与TFF1在乳腺癌细胞中显著高表达,吉非替尼可明显抑制乳腺癌细胞中H2AFJ与TFF1的表达(P<0.05,P<0.01)。结论:本研究通过生物信息学手段筛选出乳腺细胞癌组织与正常组织间差异表达基因,明确在乳腺癌发病进程中的关键基因及具有潜在治疗效果的化合物,进一步通过实验验证了所筛选药物对乳腺癌的有效性。为今后临床针对乳腺癌的新药研发提供参考,以便开发更有效的治疗方案。

Bioinformatics screening of breast cancer-related genes and potential drug research

Objective:To search the the differentially expressed genes between breast cell carcinoma tissues and normal tissues by using bioinformatics technology,and the potential therapeutic drugs for breast cancer were identified,which can provide reference for clinical immune targeted therapy and drug therapy of breast cancer in the future.Methods:"Breast cancer"was searched by using Gene Expression Omnibus(GEO),and GSE79586 chip data was downloaded.The differentially expressed genes in the control group and the breast cancer model group were screened by using bio-communication technology and subjected to GO function analysis,KEGG pathway analysis,differential gene characteristic expression analysis and protein-protein interaction network(PPI)analysis,and the analysis results were further visualized.Prognosis analysis,related function prediction and immune infiltration analysis were performed using the GEPIA,GeneMANIA,and Timer2.0 databases,respectively.Finally,the compounds with potential therapeutic effects on breast cancer are identified through Connectivity Map(CMap).Western blotting and real-time PCR(RT-PCR)were used to verify the core genes and potential therapeutic agents with the highest correlation in vitro.Results:A total of 3916 differentially expressed genes including 1786 up-regulated genes and 2130 down-regulated genes were screened.GO analysis showed that the differential genes were mainly involved in the positive regulation of phosphorylation,secretory vesicles,racemase and epimerase activities.KEGG analysis showed that differential genes were involved in systemic lupus erythematosus,alcoholism,sticky spots,amoebic dysentery Ras signal pathways and other disease pathways.The characteristic expression analysis of differential genes showed that MEK inhibitors,HSP90 inhibitors and signal transduction pathway kinase inhibitors were drugs similar to the differential genes.PPI results showed that H2AFJ,TFF1,GATA3,FOXA1,and CDH1 were core genes related to breast cancer.Two core genes of H2AFJ and TFF1 with the highest correlation were further selected for GEPIA analysis.The results of the analysis showed that the mRNA expression levels of H2AFJ and TFF1 in breast cancer cells were significantly higher than those in normal tissues,and there was a significant correlation with the pathological staging,overall survival rate and disease-free survival rate of breast cancer patients.H2AFJ and TFF1 may be potential prognostic biomarkers for survival of breast cancer patients.The functions of differentially expressed H2AFJ and TFF1 are mainly related to hormone receptor binding,epithelial structure maintenance and epigenetic negative regulation of genes,chromatin tissue involved in negative regulation of transcription,etc.The results of immune infiltration showed that the expressions of H2AFJ and TFF1 had a significant correlation with the infiltration of macrophages,neutrophils,monocytes,CD4+T,CD8+T,B lymphocytes and other immune cells.CMap results showed that compounds such as Gefitinib,Alpelisib,Sorafenib,and Sunitinib had potential therapeutic effects on breast cancer.Western blot and RT-PCR results showed that H2AFJ and TFF1 were significantly overexpressed in breast cancer cells.Gefitinib significantly inhibited the expression of H2AFJ and TFF1 in breast cancer cells(P<0.05,P<0.01).Conclusion:In this study,differentially expressed genes between breast cell carcinoma tissues and normal tissues were screened out by bioinformatics means to further identify key genes and compounds with potential therapeutic effects in the onset process of breast cancer and to further verify the effectiveness of the screened drugs on breast cancer through experiments.It will provide reference for clinical research and development of new drugs against breast cancer in the future in order to develop more effective treatment options.

基于星点设计-效应面法优化红花多糖提取工艺研究

目的:运用星点设计-效应面法探讨红花多糖的最佳提取技术工艺,并对其进行质量评价。方法:以红花多糖的提取率为指标,以料液比、提取时间、提取温度、提取次数为考察因素,在单因素试验的基础上,采用星点设计-效应面法优选出红花多糖的最佳提取工艺并验证。结果:以红花多糖提取率为因变量Y,料液比、提取时间和提取温度为自变量X,P<0.0001建立效应面模型。最佳提取技术工艺为料液比1∶16.69,提取温度91.39℃,提取工作时间89.78 min。在此条件下红花多糖提取率可达7.45%,验证实验结果显示相对标准偏差(RSD)为1.05%,证明该模型能较好地预测实验结果。结论:星点设计-效应面法优化红花多糖的提取率较高,工艺操作简便有效合理、稳定性高、精确度高,可充分发展应用于红花多糖的资源管理开发利用。

基于生物信息学筛选并综合分析肝细胞癌关键基因

目的:通过生物信息技术,检索肝细胞癌(LIHC)相关基因及对相关基因进行深入分析。方法:利用基因数据表达库(GEO)检索“LIHC“词条,下载GSE109903芯片数据,通过生信分析筛选对照组及组差异表达基因,对所获得差异表达基因进行GO功能分析、KEGG通路分析、差异基因特征表达分析并作可视化处理;蛋白互作网络分析并作可视化处理,筛选与LIHC相关性较强的核心基因EEF1A1与HK2。通过GEPIA、Kaplan-Meier plotter、GeneMANIA、Timer2.0数据库进行分析,明确LIHC关键基因的差异表达、预后价值和免疫细胞浸润情况。结果:共筛选到1 059个差异表达基因,包括637个上调基因、872个下调基因;功能分析显示差异基因主要参与以DNA为模版的正向转录调控、核体功能、核染色质功能、RNA结合等过程;通路分析显示差异基因参与系统性红斑狼疮、酒精中毒等疾病通路与RNA聚合酶Ⅰ启动子开放通路等;差异基因特征表达分析显示与差异基因特征相似的药物主要有CDC抑制剂、前列腺素、血清素受体拮抗剂、BAF转录阻遏抑制剂、酪氨酸磷酸酶抑制剂等;蛋白互作网络分析显示与LIHC相关的基因主要有EEF1A1、HK2、FAM38A、LAMB3等;选取EEF1A1与HK2两个基因进一步进行GEPIA分析,分析结果显示EEF1A1与HK2 mRNA在LIHC癌组织中表达较正常组织中高,并且与LIHC患者的病理分期和总生存率、无病生存率呈显著相关;EEF1A1与HK2可能是LIHC患者生存的潜在预后生物标志物;此外,差异表达的EEF1A1与HK2功能主要分别与翻译因子活性、分子伴侣介导的自噬和碳水化合物分解代谢过程、嘌呤核苷二磷酸代谢过程有关;免疫细胞浸润情况显示EEF1A1与HK2的表达与多种免疫细胞的浸润显著相关,包括6种类型的免疫细胞:CD4^(+)T细胞、巨噬细胞、中性粒细胞、B细胞、CD8^(+)T细胞和树突状细胞。结论:通过筛选差异表达基因,明确在LIHC发展过程中关键基因,为LIHC患者生存筛选潜在的预后生物标志物,同时本研究为LIHC临床治疗提供新思路和方案。

载Survivin-siRNA和蛇床子素阳离子脂质体纳米粒的制备工艺优化

目的:利用脂质体可同时装载水溶性成分和脂溶性成分的特点,制备载Survivin-siRNA和蛇床子阳离子脂质体纳米粒。方法:以膜材比、药脂比、超声时间和旋蒸温度为考察因素,采用正交试验法优化蛇床子素阳离子脂质体制备工艺。采用控制变量法以电位和粒径为指标,对HA-siRNA与鱼精蛋白体积比和HA-siRNA-鱼精蛋白复合物与脂质体比例进行考察。电位粒径仪测定其粒径和Zeta电位,透射电镜观察其形状;采用酶标仪测定不同浓度FAM-Survivin-siRNA标准溶液吸光度,计算载FAM-Survivin-siRNA与蛇床子素阳离子脂质体纳米粒的包封率。结果:采用薄膜分散法,通过正交试验得载蛇床子素阳离子脂质体最佳工艺为:膜材比3∶1,药脂比1∶5,旋蒸温度30℃,超声时间70 min包封率可达78.34%,通过控制变量法得载FAM-Survivin-siRNA与蛇床子素阳离子脂质体纳米粒最佳工艺为:Survivin-siRNA与鱼精蛋白体积比1∶1,鱼精蛋白复合物25μg,加入50μL阳离子脂质体。经电位粒径仪测得粒径(132.3±0.2)nm,Zeta电位(43.15±0.05)mV,其形状呈不规则的类圆形;根据标准曲线测得共载Survivin-siRNA与蛇床子素阳离子脂质体纳米粒的包封率为(81.34±0.04)%。结论:经过工艺优化制备的载Survivin-siRNA和蛇床子素阳离子脂质体纳米粒具有较好的包封率、粒径和Zeta电位。

Screening and comprehensive analysis of key genes in liver hepatocellular carcinoma based on bioinformatics

Objective:To search and analyze the related genes of liver hepatocellular carcinoma(LIHC)by using bioinformatics technology.Methods:Gene expression omnibus(GEO)was used to retrieve the entry of"Liver hepatocellular carcinoma",and GSE109903 chip data was downloaded.The differentially expressed genes in the control group and liver hepatocellular carcinoma group were screened by bioinformatics analysis.GO enrichment analysis,KEGG pathway analysis,differential gene expression analysis and visualization processing were performed for the differentially expressed genes;Protein interaction network analysis and visualization processing were used to screen core genes EEF1A1 and HK2 with strong correlation with liver hepatocellular carcinoma.GEPIA,Kaplan-Meier plotter,GeneMANIA and Timer 2.0 databases were used to analyze the differential expression,prognostic value and immune cell infiltration of key genes in LIHC.Results:A total of 1059 differentially expressed genes were screened,including 637 up-regulated genes and 872 downregulated genes.Functional analysis showed that differentially expressed genes were mainly involved in the process of positive transcription regulation,nucleosome function,chromatin function and RNA binding.Pathway analysis showed that differentially expressed genes were involved in systemic lupus erythematosus,alcoholism and RNA polymerase I promoter opening pathway.The analysis of differential gene expression showed that the drugs with similar gene characteristics were mainly CDC inhibitors,prostaglandins,serotonin receptor antagonists,BAF transcriptional repression inhibitors,tyrosine phosphatase inhibitors,etc;Protein interaction network analysis showed that the main genes associated with LIHC were EEF1A1,HK2,FAM38A and LAMB3;EEF1A1 and HK2 genes were further analyzed by GEPIA.The results showed that the expression of EEF1A1 and HK2 mRNA in LIHC tissues was higher than that in normal tissues,and was significantly correlated with the pathological stage,overall survival rate and disease-free survival rate of LIHC patients.EEF1A1 and HK2 may be potential prognostic biomarkers for LIHC patients.In addition,the functions of EEF1A1 and HK2 were mainly related to translation factor activity,molecular chaperone mediated autophagy and carbohydrate catabolism,and purine nucleoside diphosphate metabolism,respectively.Immunocyte infiltration showed that the expression of EEF1A1 and HK2 was significantly correlated with the infiltration of a variety of immune cells,including six types of immune cells:CD4+T cells,macrophages,neutrophils,B cells,CD8+T cells and dendritic cells.Conclusion:By screening differentially expressed genes,we can identify the key genes in the development of liver hepatocellular carcinoma,and screen potential prognostic biomarkers for the survival of patients with liver hepatocellular carcinoma.At the same time,this study provides new ideas and programs for clinical treatment of liver hepatocellular carcinoma.

用于治疗类风湿性关节炎的微针经皮给药系统研究进展

类风湿性关节炎是一种以慢性、炎症性为主的关节退行性疾病,因其病因复杂,目前尚无特效治疗方法。患者往往需要通过长期口服或注射非甾体抗炎药和皮质类固醇等药物以干扰验证相关通路来减轻炎症反应、延缓类风湿性关节炎(RA)进展,由此也带来诸多副作用。微针作为一种新型药物透皮给药方式,凭借其无痛微创、提高药物渗透性等优势在类风湿性关节炎治疗领域得到了应用与推广,有望成为临床治疗新策略。该文对微针在治疗类风湿性关节炎方面的应用进行总结,以期为后续新型微针的开发及扩大其临床应用提供参考。

基于VEGF/p38MAPK研究羟基红花黄色素A对过氧化氢诱导人肝细胞氧化损伤的保护作用

目的探讨羟基红花黄色素A(Hydroxysafflor yellow A,HSYA)对过氧化氢(H_(2)O_(2))诱导的人肝细胞LO2氧化损伤的保护作用及其机制。方法利用H_(2)O_(2)诱导并建立了LO2细胞氧化损伤模型。将细胞分为对照组(Control group,CG)、H_(2)O_(2)损伤模型组(Model group,MG)、HYSA(0.125,0.25,0.5,1mg·mL^(-1))干预组(MG+0.125,0.25,0.5,1mg·mL^(-1)HYSA)。分别利用MTT法、流式细胞术测定了细胞活力和凋亡程度;利用ELISA测定细胞内ROS、LDH、SOD、GSH-Px、MDA和CAT的活性及含量;Hoechst染色进一步观察细胞核凋亡状态;通过qRT-PCR技术测定细胞内VEGF、p38MAPK和凋亡相关蛋白的mRNA表达量;采用Western blotting法检测凋亡相关因子及VEGF/p38MAPK通路的蛋白表达。结果成功建立由H_(2)O_(2)所诱导的人肝细胞LO2损害模型;与MG比较,在0.125、0.25、0.5、1mg·mL^(-1)HYSA干预组细胞中LDH、MDA和ROS的活性和含量均明显下降,SOD、GSH-Px和CAT活性均明显增强,HYSA可明显抑制细胞凋亡并下调VEGF、p38MAPK/p-p38MAPK蛋白表达。结论HYSA可缓解H_(2)O_(2)对人肝LO2细胞造成的损伤,对细胞内氧化指标产生显著影响,有明显的氧化损伤保护作用,机制与VEGF/p38MAPK通路有关,可为HYSA的临床应用提供支持。

基于纳米载体的药物递送系统在类风湿性关节炎治疗中的研究进展

类风湿性关节炎是一种广泛存在的自身免疫性炎症性疾病,严重影响患者的生活质量。目前用于治疗RA的常规剂型存在诸多局限性,例如非特异性、疗效不佳、用药剂量大、给药频繁以及全身性副作用。目前,纳米技术已经能够解决传统治疗的局限性并简化疾病的复杂性,因此基于纳米技术的药物递送系统正逐渐成为一种用于RA诊断和治疗的新策略,其可使负载的抗炎药物通过主动和被动靶向至发炎区域,实现对关节的特异性、克服剂量和给药频率的增加以及与之相关的不良反应。该文旨在对近年来基于纳米载体的药物递送系统在RA领域中的最新研究进行归纳总结,并阐述如何使用纳米系统将治疗药物输送到发炎关节以控制RA进展。通过探讨目前纳米药物递送系统可能存在的问题以及亟待解决的挑战,为未来深入研究基于纳米技术的共递系统提供理论支持。

荧光内窥式共聚焦显微镜下青藤碱固体脂质纳米粒注射治疗类风湿性关节炎的研究

应用荧光内窥式共聚焦显微镜(fluorescence endoscopic laser confocal microscope,FELCM)引导关节注射青藤碱固体脂质纳米粒(sinomenine solid lipid nanoparticles,Sin-SLN),并考察体外药效评估Sin-SLN治疗类风湿性关节炎(rheumatoid arthritis,RA)的效果。采用乳化蒸发-低温固化法制备Sin-SLN,最佳处方工艺下制备的Sin-SLN包封率为64.79%±3.12%,载药量为3.84%±0.28%,测定平均粒径为(215.27±4.21)nm,Zeta电位为(-32.67±0.84)mV,初步稳定性考察中,Sin-SLN放置30 d后稳定性良好。皮下注射完全弗氏佐剂和卵白蛋白建立兔RA模型,药效实验设对照组、模型组、Sin组(1.5 mg·kg^(-1))、Sin-SLN组(1.5 mg·kg^(-1))和地塞米松组(阳性药,1.0 mg·kg^(-1),ig),对照组和模型组仅穿刺不注射药物,各实验组给予相应药物干预治疗。给药后,每日测量家兔膝关节直径及局部皮肤温度变化,与模型组相比,给药组膝关节直径和局部皮肤温度均下降;使用FELCM观测软骨形态学变化,Sin-SLN组膝关节软骨表面光滑,骨组织结构紧密;采用ELISA测定血清中白细胞介素-1(interleukin-1,IL-1)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达水平,发现Sin-SLN组血清中IL-1和TNF-α表达水平降低;与模型组相比具有显著性差异,苏木素-伊红(hematoxylin-eosin,HE)染色观察滑膜组织形态学变化,Sin-SLN组滑膜组织病变状况得到明显改善。因此,制备的Sin-SLN粒径均匀,性质稳定,通过关节注射给药形成药物贮库,Sin-SLN可有效减轻兔关节肿胀、减轻关节软骨损害,抑制炎症因子表达,抑制关节滑膜上皮增生和炎性细胞浸润,证明Sin-SLN可以有效抑制RA。

荒漠草原优势植物细根分解对土壤碳矿化与土壤养分的影响

【目的】研究宁夏东部荒漠草原优势植物细根分解对土壤碳矿化与土壤养分的影响,进一步分析优势植物细根分解动态与养分返还过程。【方法】以宁夏东部荒漠草原优势植物短花针茅(Stipa breviflora)与蒙古冰草(Agropyron mongolicum)细根为研究对象,设置对照(CK)、添加短花针茅细根(Sb)与添加蒙古冰草细根(Am)3种处理,采用室内培养法研究细根分解特征及其对土壤碳矿化与土壤养分的影响。【结果】连续培养61 d后,添加短花针茅和蒙古冰草细根显著增加土壤24 h CO_(2)释放总量、分解初期(前14 d)土壤碳矿化速率与累积CO_(2)释放量(P<0.01)。添加短花针茅与蒙古冰草细根使土壤激发效应显著增加(P<0.01),增幅为40.50%与35.28%。与CK相比,添加短花针茅和蒙古冰草细根显著增加土壤硝态氮含量(P<0.01),对土壤速效磷无显著影响。细根纤维素含量、m(C)∶m(N)与24 h CO_(2)释放总量呈显著负相关(P<0.05);细根碳含量、木质素含量、m(木质素):m(N)与24 h CO_(2)释放总量呈显著正相关(P<0.05)。细根木质素含量、m(木质素)∶m(N)与累积CO_(2)释放量呈显著正相关(P<0.05)。细根碳含量、氮含量、纤维素含量、m(N)∶m(P)与细根损失率呈显著正相关;细根木质素含量、m(木质素)∶m(N)与细根损失率呈显著负相关。【结论】植物细根初始化学性质是影响荒漠草原土壤有机碳矿化与养分循环的重要因素之一。

高分子材料载体在天然抗肿瘤药物中的研究进展

高分子材料作为在天然抗肿瘤药物载体研究领域的热点,近10年来取得了飞速的发展,尤其是在如何降低药物的毒副作用,促进药物在体内的溶解和释放,提高生物利用度方面取得了突破性的进展。现如今高分子材料作为载体应用于天然抗肿瘤药物,提高了药物的抗肿瘤的疗效,使大部分天然抗肿瘤药物制剂的开发成为可能,推动了高分子材料载体在天然抗肿瘤药物中的应用。总结并讨论了近10年高分子材料载体在天然抗肿瘤药物中的研究情况,并为后续高分子材料药物载体的开发与应用提供参考。

柚皮素纳米制剂的新剂型研究进展

柚皮素是一种具有多种生物活性的天然黄酮类化合物。但较低的水溶性和生物利用度限制了其临床应用。近年来国内外关于柚皮素纳米脂质体、纳米乳、纳米混悬剂、纳米凝胶、纳米固体分散体和纳米粒在提高溶解度、改善吸收等方面取得了一定进展。通过查阅国内外文献,对近年来柚皮素纳米新剂型研究进行综述,为其后续研发提供必要的思路和参考。

红花中抗氧化活性成分及其作用机制的研究进展

红花为菊科植物红花的干燥管状花,为活血化瘀类中药,临床上多用于治疗心脑血管疾病。适宜的抗氧化物质可以有效地消除过多自由基,对于各种氧化应激相关疾病的治疗具有重要意义。归纳了红花中的抗氧化活性成分黄酮类、多糖类和生物碱类成分,并对其抗氧化酶、清除自由基、拮抗一氧化氮的作用机制进行总结,以期为红花更好的临床应用提供参考。

基于网络药理学及体外实验验证探讨乌药抗胃癌的作用机制

利用网络药理学、分子对接技术和体外细胞实验,研究乌药抗胃癌的主要活性成分和潜在作用机制。利用中药系统药理学分析平台(TCMSP)数据库、在线人类孟德尔遗传(OMIM)和GeneCards数据库提取乌药活性成分,并预测了乌药与胃癌有关靶点。筛选二者共同的潜在功能靶位之后,再利用STRING数据库实现与二者共同靶点的蛋白相互作用(PPI)网络构建。利用DAVID数据库进行GO和KEGG富集分析;以STRING和DAVID数据库为基础,运用Cytoscape 3.7.2软件构建“活性成分-靶点”网络和“活性成分-靶点-通路”网络;利用AutoDock Vina进行分子对接,预测有效成分与关键作用靶点的结合度,最后对关键靶点和通路进行体外实验验证。预测结果共获得乌药活性成分9个、相关靶点179个,乌药与胃癌的共同靶点107个,靶点共涉及生物过程693种,细胞组成57种,分子功能129种,参与肿瘤抗原p53、缺氧诱导因子1等信号通路161条;分子对接结果显示核心成分吉马酮与TP53有较高的结合活性。最后体外实验将筛选出的乌药活性成分吉马酮对人胃癌细胞SGC-7901进行核心靶点和通路的初步验证,结果表明吉马酮可明显抑制胃癌细胞增殖并通过调控p53、Bax、Bcl-2等关键蛋白的表达来诱导SGC-7901凋亡。综上所述,乌药通过多成分、多靶点、多通路协同作用控制胃癌的发生发展,为今后临床进一步探讨乌药治疗胃癌的机制提供理论依据。

关节腔注射剂青藤碱纳米晶自稳定Pickering乳液的制备及药效学研究

目的 通过制备青藤碱纳米晶自稳定Pickering乳液(sinomenine nanocrystals self-stabilized Pickering emulsions,SinNSSPE)关节腔注射剂,在关节腔内形成药物贮库,缓慢释放以提高生物利用度,降低药物毒副作用,以青藤碱纳米晶(sinomeninenanocrystal,Sin-NCs)自身为稳定剂制备Sin-NSSPE关节腔注射剂,用药效学实验考察其对类风湿性关节炎(rheumatoid arthritis,RA)的治疗效果。方法 通过药物质量浓度、油水相比例和水相pH值等因素对Sin-NSSPE进行优化,运用福氏佐剂关节炎方法建立RA大鼠模型,以关节肿胀度、关节炎指数、脾指数、酶联接免疫吸附剂测定(enzyme-linked immunosorbnent assay,ELISA)、组织病理学检查、Western blotting法作为指标进行检测。结果 结果显示Sin-NSSPE的粒径均匀,载药量良好,Sin-NCs的平均粒径为(121.49±18.26)nm、Sin-NSSPE的粒径为(1 159.60±160.15)nm、载药量4.92mg/mL;药效学实验结果显示,与青藤碱ig组相比,Sin-NSSPE关节腔注射组能有效降低关节肿胀度和炎症指数,改善滑膜组织的病变、抑制关节炎症。青藤碱关节腔注射组和Sin-NSSPE关节腔注射组均能明显改善大鼠关节肿胀,降低滑膜组织中炎症因子白细胞介素-1(interleukin-1,IL-1)、IL-6、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达(P<0.05、0.01),且Sin-NSSPE关节腔注射组治疗效果优于青藤碱关节注射组,同时剂型稳定性提高并形成药物贮库,使药效更加平稳。结论 制备的Sin-NSSPE性质稳定,Sin-NSSPE关节腔注射对大鼠RA有良好的疗效。

Age-related differences in the biological parameters of vertebral cancellous bone from Chinese women

Background With aging, the human fracture risk gradually increase. This is mainly due to the corresponding changes of the biomechanical parameters of human bone presents with aging. We measured the microstructural parameters of lumbar bone from women in several age groups by micro-computed tomography and scanning electron microscopy. We observed changes in lumbar cancellous bone mineral density and in biomechanical parameters with aging to elucidate the relationship between age and risk of fracture. We provide theoretical support for human pathology, fracture risk increased with age and the individualized of each age group.