抗肿瘤药物萃析及进展

目的研析抗肿瘤药物,增加国内外抗肿瘤药物信息。方法查阅文献并分类总结。结果国内外抗肿瘤药物较多,信息量大。结论对国内外抗肿瘤药物信息的分析总结可增加对抗肿瘤药物信息的把握,利于合理应用该类药物。     

基于合成致死的抗肿瘤药物研发进展

合成致死是指在两个非致死基因中任何一个基因发生突变均不影响细胞存活,但当两个基因同时发生突变时,能够特异性导致细胞死亡。恶性肿瘤由于DNA复制和修复的错误积累了大量的基因突变,因此可抑制与这些基因具有合成致死关系的另一个基因,从而选择性地杀死肿瘤细胞,而不影响正常细胞。近年来,合成致死原理已经成功应用于肿瘤的靶向治疗。本文综述了合成致死的基本原理、合成致死相互作用的筛选方法、合成致死在DNA损伤修复领域的研究现状、合成致死在抗肿瘤药物研发中的挑战及展望。     

靶向抗肿瘤纳米药物研究进展

肿瘤是当今严重威胁人类健康的三大疾病之一。然而目前在临床肿瘤治疗和诊断中广泛应用的药物还多数为非选择性药物，体内分布广泛，尤其在一些正常组织和器官中也常有较多分布，常规治疗剂量即可对正常组织器官产生显著的毒副作用，导致患者不能耐受，降低药物疗效，所以提高药物的肿瘤选择性，减少其在非靶向部位的聚集是提高抗肿瘤药物疗效的关键。减少药物对非靶向部位的毒副作用，降低药物治疗剂量并减少给药次数，从而提高药物疗效，这种治疗方法即被称为肿瘤靶向治疗。现今在肿瘤靶向治疗领域，靶向抗肿瘤纳米药物研究正日益受到人们的普遍关注和重视，现就其近年来的研究进展综述如下。     

抗肿瘤药物市场现状分析及其启示

随着社会人口老年化、生活压力的增加以及环境的污染等，癌症发病率逐年增加，癌症时人类的威胁日益增大，它已经成为世界威胁人类健康的第二大杀手。本文通过对全国16个重点城市257家医院的抗肿瘤医院用药总体情况进行市场份额、增长率、品种潜力、各类别的抗肿瘤药物市场份额、各品种的抗肿瘤药物市场份额以及市场集中度等方面进行分析，并结合政府出台的一系列的医药政策的影响．时目前抗肿瘤药物的医院市场情况，市场未来预测以及抗肿瘤药物的未来研发方向等进行了探讨。     

抗肿瘤寡肽类抗肿瘤药物研究进展

目前肿瘤已成为仅次于心脑血管疾病的第二大杀手,各种抗肿瘤药物的研究和开发也因此成为医药生物研发领域的热点.抗肿瘤肽类药物因具有分子质量小、多存在内源性靶点、极易穿透肿瘤细胞、提高免疫应答、抑制肿瘤血管形成、抑制肿瘤生长和转移等特点,已成为肿瘤治疗研究的一个新热点.一般将10个以下氨基酸缩合而成的肽类称为寡肽,10个以上氨基酸缩合而成的肽类称为多肽.国外研究人员已筛选出数十种抗肿瘤寡肽类物质,并经实验证明可以有效抑制肿瘤生长或预防肿瘤的发生,中国也正致力于研发新的抗肿瘤寡肽类药物,其中包括酪丝亮肽(tyroserleutide,YSL)和酪丝缬肽(tyroservaltide,YSV)等.本文主要从近年来寡肽类药物的抗肿瘤作用机制以及抗肿瘤寡肽类药物酪丝亮肽和酪丝缬肽的最新研究进展展开论述.     

支气管哮喘药物治疗进展

支气管哮喘是有多种细胞(如嗜酸性粒细胞、肥大细胞、T淋巴细胞、中性粒细胞、气道上皮细胞等)和细胞组分参与的气道慢性炎症性疾病.通常出现广泛多变的可逆性气流受限,并引起反复发作的喘息、气急、胸闷和咳嗽等症状,常在夜间和(或)清晨发作、加剧,多数患者可自行缓解或经治疗缓解.不正确的治疗可导致哮喘的反复发作.     

慢性前列腺炎的药物治疗进展

慢性前列腺炎是男性泌尿生殖系统常见且处理颇为棘手的一组综合征,慢性无菌性前列腺炎和慢性盆腔疼痛综合征更为多见。近几年来随着研究的深入,对其分类、病因及治疗有了新的进展。现就其药物治疗进展及相关内容介绍如下。1前列腺炎的分类前列腺炎传统的分类包括急性细菌性前列     

不同蒽环类抗肿瘤药物在急性白血病化疗中疗效观察

目的分别应用阿霉素、米托蒽醌、吡柔比星作为急性白血病化疗的主要药物,观察3种蒽环类抗肿瘤药物对急性白血病化疗的疗效和毒副作用差异.方法采用随机方法将90例首治或复发的急性白血病患者分为3组,分别使用阿霉素、米托蒽醌、吡柔比星作为主要的化疗药物,观察3组周围血象、骨髓象的变化及毒副作用.结果3组总有效率无差异(p>0.05).阿霉素心脏毒性高于米托蒽醌和吡柔比星;脱发发生率阿霉素与米托蒽醌相近但均高于吡柔比星;骨髓抑制方面米托蒽醌高于阿霉素和吡柔比星;3种药物中吡柔比星毒副作用最低(p<0.05).结论3种药物均为治疗急性白血病的有效药物.吡柔比星抗肿瘤活性高,毒副作用较低,有推广价值.     

抗肿瘤纳米药物新剂型研究启动

<正>日前,国家重大科学研究计划项目基于纳米技术的药物新剂型改善肿瘤治疗效果的应用基础研究启动会在中国科学院上海药物研究所召开。     

抗肿瘤药物研究新进展

目的:肿瘤是人体内正在发育的或成熟的正常细胞,在外来和内在有关因素长期作用下,出现过度增生成异常分化而形成的新生物。它与正常的组织和细胞相比,有一些特异性,肿瘤的靶向治疗常基于此。近年来,随着研究的不断深入,新的观点和治疗思路不断涌现,本文将概述近年来肿瘤研究领域的新进展。     

门诊精神病患者应用BZD类药物的调查

目的 了解我院门诊复诊精神病人BZD类药品的使用情况和疗效评定。方法 采用“一日统计学”对门诊复诊精神病人使用BZD类药品用量、药品使用频度等项目进行统计,对使用BZD类药品的复诊452例精神病患者．按照联合使用BZD类药品或未使用BZD类药品的使用标准随机分成两组,比较BZD类药品的疗效。结果 门诊复诊使用APD类和BZD类药品联合用药的精神病患者,使用BZD类药品的用量明显降低;两组疗效比较,联合使用药品治疗的疗效与单独使用APD类药品疗效无显著性差异;且使用BZD类药品维持治疗的时间过长。结论 精神病患者并非必须使用BZD类药品。     

Anti-tumour effects of PIM kinase inhibition on progression and chemoresistance of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers. Yet to date, the potential application of PIM inhibitors in HCC is still largely unexplored. In the present study we investigated the pre-clinical efficacy of PIM inhibition as a therapeutic approach in HCC. Effects of PIM inhibitors on cell proliferation, migration, invasion, chemosensitivity, and self-renewal were examined in vitro. The effects of PIM inhibitors on tumour growth and chemoresistance in vivo were studied using xenograft mouse models. Potential downstream molecular mechanisms were elucidated by RNA sequencing (RNA-seq) of tumour tissues harvested from animal models. Our findings demonstrate that PIM inhibitors SGI-1776 and PIM447 reduced HCC proliferation, metastatic potential, and self-renewal in vitro. Results from in vivo experiments supported the role of PIM inhibition in suppressing of tumour growth and increasing chemosensitivity of HCC toward cisplatin and doxorubicin, the two commonly used chemotherapeutic agents in trans-arterial chemoembolisation (TACE) for HCC. RNA-seq analysis revealed downregulation of the MAPK/ERK pathway upon PIM inhibition in HCC cells. In addition, LOXL2 and ICAM1 were identified as potential downstream effectors. Taken together, PIM inhibitors demonstrated remarkable anti-tumourigenic effects in HCC in vitro and in vivo. PIM kinase inhibition is a potential approach to be exploited in formulating adjuvant therapy for HCC patients of different disease stages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Anti-tumour synergy of cytotoxic chemotherapy and anti-CD40 plus CpG-ODN immunotherapy through repolarization of tumour-associated macrophages

We studied the effectiveness of monoclonal anti‐CD40 + cytosine–phosphate–guanosine‐containing oligodeoxynucleotide 1826 (CpG‐ODN) immunotherapy (IT) in mice treated with multidrug chemotherapy (CT) consisting of vincristine, cyclophosphamide and doxorubicin. Combining CT with IT led to synergistic anti‐tumour effects in C57BL/6 mice with established B16 melanoma or 9464D neuroblastoma. CT suppressed the functions of T cells and natural killer (NK) cells, but primed naïve peritoneal macrophages (Mφ) to in vitro stimulation with lipopolysaccharide (LPS), resulting in augmented nitric oxide (NO) production. IT, given after CT, did not restore the responsiveness of T cells and NK cells, but further activated Mφ to secrete NO, interferon‐γ (IFN‐γ) and interleukin (IL)‐12p40 and to suppress the proliferation of tumour cells in vitro. These functional changes were accompanied by immunophenotype alterations on Mφ, including the up‐regulation of Gr‐1. CD11b⁺ F4/80⁺ Mφ comprised the major population of B16 tumour‐infiltrating leucocytes. CT + IT treatment up‐regulated molecules associated with the M1 effector Mφ phenotype [CD40, CD80, CD86, major histocompatibility complex (MHC) class II, IFN‐γ, tumour necrosis factor‐α (TNF‐α) and IL‐12] and down‐regulated molecules associated with the M2 inhibitory Mφ phenotype (IL‐4Rα, B7‐H1, IL‐4 and IL‐10) on the tumour‐associated Mφ compared with untreated controls. Together, the results show that CT and anti‐CD40 + CpG‐ODN IT synergize in the induction of anti‐tumour effects which are associated with the phenotypic repolarization of tumour‐associated Mφ.     

Block Co-polymer Nanoparticles with Degradable Cross-Linked Core and Low-Molecular-Weight PEG Corona for Anti-tumour Drug Delivery

Biodegradable/bioeliminable, core-cross-linked, block co-polymer nanoparticles have been synthesized as a potential anti-tumour drug-delivery system. Methacrylate-modified poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-b-PDLLA) composed of low-molecular-weight polymer blocks (<5 kg/mol) were synthesized by ring-opening polymerization and post-polymerization chemical modifications. Nanoparticles with a diameter of 110 ± 20 nm were formed from methacrylate-modified PEG₄₅-b-PDLLA₄₁ in a THF/water mixture (1:3). The particles were then core-cross-linked using a new, highly acid-labile ketal cross-linker. The cross-linked particles had a hydrodynamic diameter of 104 ± 20 nm (in THF/water, 1:3), as determined by DLS. The particles in THF exhibited a similar hydrodynamic diameter. Doxorubicin as a model anti-tumour drug was loaded into the nanoparticles (25–31 wt%). The particles released 50% of the loaded drug slowly approximately in 2 days at pH 5.5 and in 5 days at pH 7.4. The particles degraded to bioeliminable polymer fragments (<40 kg/mol) after the hydrolysis of the ketal cross-links at pH 5.5 in seven days, as determined by GPC. Doxorubicin-loaded cross-linked particles (9.3 μM doxorubicin/2.5 μM polymer) inhibited the viability of human neuroblastoma SH-EP cells, whilst the particles without drug at the same concentration were non-toxic, as determined by an Alamar Blue assay. Flow cytometry experiments revealed that the doxorubicin-loaded cross-linked particles were taken up by SH-EP cells in quantities comparable with free doxorubicin. Overall the results support the value of the cross-linked particles for further investigation as a carrier for anti-tumour drugs.     

Anti-tumour cytotoxin from macrophages: no correlation between cytotoxin adsorption by tumour cell lines and their cytotoxin susceptibility.

Mononuclear phagocytes can synthesize a cytotoxin, similar to that in tumour necrosis serum, which is cytotoxic to certain tumour cell lines in vitro. This study has investigated whether susceptibility and resistance to the cytotoxin can be explained in terms of the amount of cytotoxin receptor expressed on the tumour cell surface. Binding of cytotoxin has been quantitated both by direct adsorption and competitive inhibition assays with cytotoxin-resistant or -susceptible tumour lines and with sublines of susceptible lines, selected for resistance to the cytotoxin. For both rabbit and human cytotoxin, there was no correlation between cytotoxin adsorption by tumour cell lines and their cytotoxin susceptibility, suggesting that resistance to the cytotoxin is expressed at a post-receptor stage. Preliminary studies on the cytotoxin receptor of K562 cells have shown that it is probably not the transferrin receptor, and that protein but not carbohydrate is essential for its function.     

三维完美主义量表的编制和信效度检验

目的 根据Hewitt的理论编制三维完美主义量表,检验其信度、效度.方法 174名大学生回答新编项目,采用探索性因素分析、验证性因素分析确定量表结构与项目保留,选用内部一致性系数检验量表的信度.结果 因素分析表明因素结构与量表编制的理论构想一致,最后确定量表为3个维度、25项,各维度及总量表的α值在0.67～0.83之间.结论 三维完美主义量表具有很好的项目区分度、信度、效度.     

大学生心理危机测验的编制及信效度检验

目的 编制适合我国大学生心理危机干预测验.方法 252名大学生回答新编项目,采用探索性因素分析、验证性因素分析确定测验结构与项目保留,选用内部一致性系数检验测验信度.结果 因素分析表明因素结构与测验编制的理论构想一致,最后确定测验包括生理症状、情绪症状、认知症状、行为症状及自杀意念等5个分测验计58项,各维度及总测验的α值在0.63～0.93之间.结论 心理危机测验具有良好的信度、效度,能够全面、准确地评价大学生心理危机的水平,为大学生心理危机干预提供客观依据.     

震颤信号分析的研究现状及展望

震颤是人身体某一个或多个功能区肌肉的节律性、不自主振动,是运动神经元异常同步化的结果。用信号处理的方法检测分析震颤患者加速度(accelerometer,ACC)、表面肌电(electromyography,EMG)、脑电(electroencephalography,EEG)信号对震颤临床诊断、等级评定、疾病早期发现等方面具有重要意义。介绍了时域分析、频域分析、人工神经网络、高阶谱、近似熵、模糊、浑沌、判别分析等方法在震颤信号研究中的应用情况,最后展望了震颤信号分析的应用前景。     

我国医院信息化现状分析及发展对策

本文探讨了医院信息化建设的重要性。通过对比国内外医院信息化建设的现状,指出我国医院信息化建设中的不足,分析我国医院在信息化建设中遇到的问题,并给出问题的解决建议。     

军官职业人格量表的初步编制

目的：编制一个中国军官职业人格量表,检验其信度和效度.方法：建构军官职业人格理论模型,并依照该模型编制了军官职业人格量表.量表的有效样本1390名军官,间隔10天的重测样本70名军官,用因子分析和相关分析考察量表的信度和效度.结果：新编量表的项目间平均相关系数（MIIC）为0.19-0.31,Cronbachα系数为0.47-0.92,分半信度为0.41-0.85,重测信度为0.692-0.918;探索性因子分析的结果与量表编制者的理论构想基本一致.结论：军官职业人格量表具有较好的信度和效度,可以用于军官心理教育、训练和选拔实践.