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??Tacrolimus is widely used as a first-line immunosuppressant after adult liver transplantation. However, because of narrow treatment window and pharmacokinetic individual differences, it is difficult to formulate individualized dosing regimens in short term. Pharmacokinetic parameters that estimated by population pharmacokinetics(PPK) can provide a preliminary individualized regimen for early postoperative patients. This paper collected literatures on PPK modeling of orally administered tacrolimus in adult liver transplantation patients through literature search. And multiple influencing factors of PPK model was mainly summarized, such as demographic characteristics, blood biochemical index, combined medication, liver and kidney function, genetic factors, postoperative time and dosage. It will provide literature support for the development of individualized dosing regimens for oral tacrolimus recipients using the PPK protocol for adult liver transplantation.     

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??Ideal preparation of cancer therapy could specifically target to tumor cells, serving as safe and effective drug delivery system. With peculiar molecular recognition ability, aptamers become the most promising biological target molecules. This review was based on representative literatures,and the data was summarized and analyzed. It summarizes the latest research progress of aptamers modified targeted tumor preparation in the past five years from tethered way and carriers type, and the existing problems are analyzed and prospected.     

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??Multidrug resistance of tumor cells is a material cause of chemotherapy failure, and the overexpression of adenosine triphosphate-binding cassette(ABC) membrane transporters is an important factor in multidrug resistance. Significant progress has been made in reversing multidrug resistance by reducing the expression of drug transporters on tumor cells; inspired by the mechanism of multidrug resistance,speeding up the efflux of poisons by increasing the expression of drug transporters is attracting more and more attention. In this review, We summarized the research progress on mechanism of membrane transp-orters in drug resistance in recent years, and new mechanism of detoxification based on these theories.     

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??A disintegrin-like and metalloprotease(ADAMTS) proteinases are a group of multidomains and secreted metalloproteinases containing the thrombospondin motifs. ADAMTS-7 is a member of ADAMTS family and plays a crucial role in the cardiovascular diseases. In physically, ADAMTS-7 was involved in the growth and development of the body. However, in pathological conditions, over expression of ADAMTS-7 gene accelerated the progression of cardiovascular diseases through by promoting the breakdown of cartilage oligomeric matrix protein (COMP) matrix. Meantime, the over expression of ADAMTS-7 can be effectively inhibited by TGF-??, miRNA29a/b, and then effectively retarded the development of cardiovascular disease. This article mainly reviews the gene structure, protein function and the mechanism of ADAMTS-7 involved in cardiovascular diseases and looks forward to the possibility of ADAMTS-7 as a new target for the treatment of cardiovascular diseases.     

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??Many neurodegenerative diseases are closely linked with neuroinflammation, microglia is one of the important participants, which plays an important role in physiological and pathological states. Therefore, inhibiting the excessive activation of microglia will be the potential drug targets of control neuroinflammation. Recent studies have found resveratrol in the central nervous system have a neuroprotective effect, which related to the inhibition of microglia activation and control of neuroinflammation. In this study, its possible mechanisms will be reviewed.     

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??The aim of the article is to analyze recent studies on the role of mitophagy in cardiovascular diseases and related mechanism. Under normal circumstances, mitophagy is able to maintain the stability of the mitochondrial function, thus ensuring the normal operation of cardiac function, while mitophagy abnormalities are closely associated with cardiovascular diseases. Mitophagy plays an important role in the prevention and treatment of cardiovascular diseases. But the complex mechanism of action needs further researchment.     

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??To analyze recent studies on the role of transient receptor potential vanilloid 4(TRPV4) in fibrosis diseases and related mechanism. TRPV4 is a class of non-selective cation channel protein, which involved in intracellular divalent cations, mainly regulate Ca²⁺ homestasis and participate in the development of multiple organ fibrosis broadly. TRPV4 plays an important role in the prevention and treatment of fibrosis diseases. But for its complex mechanism of action, further research needs to be studied.     

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??As a medicine and food homology plant, licorice has received extensive attention from many pharmacologists and biologists. The authors reviewed the new biotechnologies applied to licorice in recent years, including the research on the key enzyme genes involved in the biological synthetic pathway of the active constituents, the formation mechanism of genuineness based on genes, the gene regulation of the biosynthesis of active components, and DNA identification of licorice, aiming to bring up some ideas for deeper studies of licorice.     

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??High-dose methotrexate can obviously reduce tumor recurrence and prolong disease-free survival. But in actual clinical use, the pharmacokinetics and toxicity of the drug show large interpatient variability. Metabolic enzyme and transporter gene polymorphisms may be one of the important influence factors, which are the research focus in recent years. However, different research shows various results. We reviewed the results of related literatures in recent years and the influence of gene polymorphisms of metabolic enzyme and transporter on pharmacokinetic and toxicity of methotrexate were summarized, which can provide information support for the further study of the individualized treatment of methotrexate.     

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??OBJECTIVE To investigate the impact factors of the semi-quantitative Western blot (WB), offering a guidance on research of pharmacological effects of drugs at the level of proteins. METHODS Total proteins were extracted from the Huh7.5 cells infected with hepatitis C virus and quantified with BCA kit, HCV Core protein was chose as target protein, and protein Tubulin or Gapdh, which was encoded by housekeeping gene, as the internal control. By controlling the experimental factors, such as loading sample amount, concentration and the incubation time of first antibodies, and dilutions of chemiluminescent fluid as well, we analyzed those factors how to impact the semi-quantitative results. RESULTS The semi-quantitative results showed that there is a linear relationship between relative intensity of target protein and the amount of total protein at must protein concentration range, beyond which, the rangeability of relative intensity of target protein reduced, even no changes. However, sample volume loaded, or protein selected as internal reference has little influence on the result of semi-quantitative WB. In the context of obtaining high-quality band, concentration and incubation time of antibodies or dilution of chemiluminescent fluid also has no influence on it. Yet, the semi-quantitative WB has certain defects and our results show that the permissible error of semi-quantitative result should be controlled within 15%. CONCLUSION The key impact factor on the result of semi-quantitative WB is the target protein amount of loading. On the premise of obtaining clear and high-quality bands, appropriately selecting loading volume of samples, concentration and incubation time of first antibodies, and dilutions of chemiluminescent fluid is conducive to accomplish experiments without affecting the final results of semi-quantitative WB.
     

中医药调控血管生成拟态机制的研究进展

血管生成拟态(VM)是近年来发现的肿瘤新生血管形成的新的形式,与肿瘤细胞的侵袭转移和肿瘤患者的不良预后有着密切的关系。乏氧微环境、促血管生成因子、PI3K、ERK1/2等多种细胞因子和信号通路参与肿瘤组织中VM的形成。肿瘤干细胞、上皮间质转化等促进肿瘤进展的因素也与VM关系密切。中医药对VM的形成具有一定的干预作用,文章即对VM的形成机制以及中医药对VM的调控及重塑肿瘤细胞的功能作用做一综述。     

消痰散结方对血管生成拟态相关蛋白表达的影响

目的探讨消痰散结方对血管生成拟态（VM）相关蛋白表达的影响。方法30只裸鼠皮下移植人胃癌瘤块建立荷瘤模型。造模后的荷瘤鼠随机分为生理盐水组、消痰散结组、盐酸多西环素组,每组10只,分别给予相应药物灌胃治疗4周后,脱颈椎处死荷瘤鼠。观察移植瘤中VM的形态结构,计数VM的数量;运用免疫组织化学法检测肿瘤中基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）和层黏连蛋白5γ2链（LN-5γ2）等VM相关蛋白的表达。结果人胃癌裸鼠移植瘤可以形成VM。消痰散结组和盐酸多西环素组VM数量明显少于生理盐水组,差异有统计学意义（P〈0．01）。消痰散结组和盐酸多西环素组MMP-2、MMP-9和LN-5γ2蛋白的阳性表达低于生理盐水组,差异均有统计学意义（P〈0．01）。结论消痰散结方可抑制裸鼠移植瘤VM的形成,其机制可能与下调MMP-2、MMP-9和LN-5γ2蛋白表达有关。     

抑癌方对结肠癌转移潜能及血管生成拟态的影响

目的:观察结肠癌细胞的转移潜能(迁移、侵袭力)是否和血管生成拟态(VM)存在相关性;探讨抑癌方对结肠癌转移潜能的影响,及其机制是否与VM有关。方法:以实验中可以形成VM的人结肠癌细胞为VM(+)组,不能形成VM的人结肠癌细胞为VM(-)组,划痕、Transwell侵袭实验观察其迁移、侵袭能力;对VM(+)组细胞进行后续实验,分组如下:抑癌方处理过的中药组和未经处理的空白对照组,划痕、侵袭实验观察其迁移、侵袭能力,体外三维培养法观察其血管生成拟态的形成情况。结果:三维培养环境下,人结肠癌细胞株HCT116可以形成VM为VM(+)组,HT29不能形成VM为VM(-)组,VM(+)组的迁移、侵袭力明显强于VM(-)组(P<0.05),且VM密度和细胞的迁移呈正相关(r=0.994,P<0.05),VM密度和侵袭力呈显著正相关(r=0.998,P<0.05);经抑癌方处理的中药组其迁移、侵袭力明显弱于未处理的对照组(P<0.05),中药组的VM密度和对照组相比差异有统计学意义(P<0.05)。结论:结肠癌的迁移、侵袭能力和VM存在相关性,抑癌方可以抑制结肠癌细胞的迁移和侵袭能力,其机制可能和抑制VM的形成有关。     

抑癌方对结肠癌转移潜能及血管生成拟态的影响

目的:观察结肠癌细胞的转移潜能(迁移、侵袭力)是否和血管生成拟态(VM)存在相关性;探讨抑癌方对结肠癌转移潜能的影响,及其机制是否与VM有关。方法:以实验中可以形成VM的人结肠癌细胞为VM(+)组,不能形成VM的人结肠癌细胞为VM(-)组,划痕、Transwell侵袭实验观察其迁移、侵袭能力;对VM(+)组细胞进行后续实验,分组如下:抑癌方处理过的中药组和未经处理的空白对照组,划痕、侵袭实验观察其迁移、侵袭能力,体外三维培养法观察其血管生成拟态的形成情况。结果:三维培养环境下,人结肠癌细胞株HCT116可以形成VM为VM(+)组,HT29不能形成VM为VM(-)组,VM(+)组的迁移、侵袭力明显强于VM(-)组(P<0.05),且VM密度和细胞的迁移呈正相关(r=0.994,P<0.05),VM密度和侵袭力呈显著正相关(r=0.998,P<0.05);经抑癌方处理的中药组其迁移、侵袭力明显弱于未处理的对照组(P<0.05),中药组的VM密度和对照组相比差异有统计学意义(P<0.05)。结论:结肠癌的迁移、侵袭能力和VM存在相关性,抑癌方可以抑制结肠癌细胞的迁移和侵袭能力,其机制可能和抑制VM的形成有关。     

消痰散结方对人胃癌裸鼠移植瘤血管生成拟态的影响

目的 探讨消痰散结方对人胃癌裸鼠移植瘤血管生成拟态（vasculogenic mimicry,VM）的影响及其机制。 方法 30只裸鼠右前肢腋部皮下移植人胃癌瘤块建立荷瘤模型。造模后的荷瘤鼠随机分为模型组（10只）、消痰散结组（10只）和多西环素组（10只）,分别给予相应药物灌胃治疗4周后,脱颈椎处死荷瘤鼠。剥取肿瘤,称取瘤质量,计算抑瘤率;计数肿瘤中VM的数量;运用免疫组织化学法检测肿瘤中基质金属蛋白酶2（matrix metalloproteinase-2,MMP-2）和基质金属蛋白酶9（matrix metalloproteinase-9,MMP-9）蛋白的表达。     

膜突蛋白在肝细胞癌表达的研究进展

膜突蛋白(Moesin)与肿瘤关系密切,但是目前对膜突蛋白与人类肝癌关系的研究尚少,尤其是中医药防治肝细胞癌的研究甚少。本文综述了近5年来膜突蛋白对肝癌细胞恶性增殖的影响及其在人肝细胞癌中的表达及意义,并对目前存在的问题及今后的研究前景进行了思考与展望。     

中医药治疗肝癌简况

肝细胞癌可归属"积聚""癥瘕"等范畴,多正虚邪实。正气不足,肾精不足,脾胃虚弱,气滞血瘀等是肝癌发生发展的病理基础。针刺对神经内分泌激素和细胞因子的生成和表达有一定影响,可调节机体神经-内分泌-免疫等系统,使肝癌向有利的方向转化,对肝癌的发生发展有一定的抑制作用。艾灸功效独特,操作简便、安全,适应证广,毒副作用,有提高免疫力作用。中药治疗基本原则是祛邪扶正,不同阶段,应掌握祛邪与扶正时机:早期正气充足主要祛除邪气;中期机体正气不足,不能抵抗邪气,宜攻补兼施;晚期正气耗损严重,应补虚扶正为主,兼以祛邪抗癌;包括资生丸等健脾化瘀药内服及逐水药、止痛贴等外敷。     

蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、调亡的关系

目的：探讨蜂毒素抑制骨肉瘤裸鼠移植瘤的作用及机制。方法：建立裸鼠骨肉瘤原位移植瘤模型,裸鼠18只,随机分3组：生理盐水组,蜂毒素组,顺铂组。观察各组裸鼠骨肉瘤体积和瘤体质量抑制率;应用免疫组化CD34与PAS双重染色法检测各组裸鼠瘤体血管生成拟态密度;免疫组织化学法检测增值细胞核抗原（PCNA）蛋白表达;TUNEL法检测肿瘤细胞凋亡;运用相关性分析法研究蜂毒素抑制骨肉瘤血管生成拟态与影响肿瘤细胞增殖、凋亡的关系。结果：蜂毒素组瘤体积和瘤体质量抑制率分别为42.98%、39.03%,蜂毒素能明显抑制CD34与PAS双重染色法标记的肿瘤血管生成拟态密度,能明显抑制肿瘤细胞增殖、促进细胞凋亡,且蜂毒素抑制肿瘤血管生成拟态密度与肿瘤细胞增殖呈正相关、与细胞凋亡呈负相关。结论：蜂毒素具有抑制骨肉瘤裸鼠移植瘤生长的作用,其作用机制可能与其能够抑制肿瘤血管生成拟态、诱导肿瘤细胞凋亡、抑制细胞增殖有关     

动力素kinectin基因mRNA在7404肝癌细胞株的表达及意义

目的研究动力素作为肝癌相关抗原其在肝癌细胞株中的表达情况,评价其作为分子肿瘤标记以及肿瘤免疫治疗特异性靶位的可能性。方法运用RT-PCR技术检测国内建株的肝癌细胞株BEL-7404 kinectin基因(D2剪接区)mR-NA的表达,并与肝癌组织、相应癌旁肝组织、正常肝组织比较。结果肝癌细胞株BEL-7404中kinectin基因(D2选择剪接区)呈强阳性表达,肝癌组织中也呈较强的阳性表达,癌旁肝组织则表达呈弱阳性。结论 kinectin基因可作为肝癌诊断的辅助分子标记,并具有作为肝癌免疫治疗特异性靶位的潜在价值。