索拉非尼与舒尼替尼单药治疗晚期肝细胞癌的效果分析

目的:对比索拉非尼(Sorafenib)和舒尼替尼(Sunitinib)单药治疗晚期肝细胞癌的疗效及安全性。方法:对我院2004年1月-2010年10月收治的44例晚期肝细胞肝癌患者的临床资料进行回顾分析。根据不同给药方式,将患者分为两组。其中,索拉非尼组32例患者采取口服索拉非尼进行治疗,而舒尼替尼组12例患者给予口服舒尼替尼治疗。观察并比较两组患者的治疗效果及药物不良反应情况。结果:索拉非尼组总生存时间为6.3月,1年生存率为16%,肿瘤进展时间为3个月,疾病控制率为71%;舒尼替尼组总生存时间为4.7月,1年生存率为8%,肿瘤进展时间为3个月,疾病控制率为64%。两组临床效果差异无统计学意义(P=0.2415,0.5706,0.7132)。索拉非尼组患者手足皮肤反应、中性粒细胞减少及肝损伤等主要毒副反应的发生率均低于舒尼替尼组,差异具有统计学意义(P0.05)。结论:索拉非尼治疗晚期肝细胞肝癌的临床效果与舒尼替尼具有很好的一致性,药物不良反应相对较轻,患者依从性较好,值得临床推广应用。     

肾透明细胞癌MAPK9的表达与索拉非尼疗效的关系

目的:探讨肾透明细胞癌组织中MAPK9表达及其与肾透明细胞癌主要临床病理特征之间的关系,分析MAPK9对索拉非尼靶向治疗疗效的关系。方法:回顾分析2006年5月-2013年10月经病理确诊的32例肾透明细胞癌转移患者的MAPK9的表达情况。所有患者术后均服用索拉菲尼并随访;同时选取10例距肿瘤3 cm癌旁正常肾组织作为对照。对比分析肾透明细胞癌患者与对照组MAPK9的阳性表达率,分析MAPK9阳性表达与疗效的相关性,并分析MAPK9阳性表达与生存率之间的关系。结果:肾透明细胞癌组MAPK9阳性表达21例(65.6%),较正常对照组2例(20.0%)有显著性差异(P0.01)。TNMⅠ~Ⅱ期MAPK9阳性表达12例(85.7%),较TNMⅢ~Ⅳ期10例(55.6%)有显著性差异(P0.05);核分级1~2级MAPK9阳性表达18例(81.8%),较3~4级4例(40.0%)有显著性差异(P0.05)。MAPK9阳性表达患者与阴性表达患者疗效有显著性差异(P0.05)。MAPK9阳性患者PFS为(646±103)d,较阴性患者PFS为(502±89)d,有显著性差异(P0.05)。MAPK9阳性患者OS为(866±75)d,较阴性患者OS为(657±62)d,有显著性差异(P0.01)。结论:MAPK9在肾透明细胞癌中高表达,与肿瘤的临床TNM分期、病理分级相关。MAPK9阳性表达患者其靶向治疗疗效越好,提示MAPK9可能是一个预测索拉菲尼靶向治疗肾透明细胞癌疗效的潜在因子。     

三维适形放疗与调强放疗对晚期非小细胞肺癌患者血清肿瘤标志物及剂量学参数比较研究

目的:对比晚期非小细胞肺癌患者经三维适形放疗(3D-CRT)与调强放疗(IMRT)后,其血清肿瘤标志物及剂量学参数的变化。方法:选择2015年1月-2016年12月期间我院收治的非小细胞肺癌患者120例,根据放疗方案将其分为IMRT组60例与3D-CRT组60例。比较两组临床疗效、药物毒副反应、1年内的生存率、放射剂量参数,以及治疗前与治疗后血清肿瘤标志物的变化。结果:IMRT组治疗的总有效率与3D-CRT组对比差异无统计学意义(P0.05)。IMRT组血小板减少、Ⅲ度放射性食管炎、Ⅲ度消化道反应、Ⅲ度放射性肺炎、Ⅲ度白细胞减少的发生率均低于3D-CRT组(P0.05)。IMRT组1年内的生存率90.00%,高于3D-CRT组的75.00%(P0.05)。IMRT组CI值与HI值均高于3D-CRT组(P0.05),IMRT组与3D-CRT组平均剂量对比差异无统计学意义(P0.05)。治疗后两组鳞状细胞癌抗原(SCC)、细胞角蛋白19片段抗原21-1(CYFRA21-1)与肿瘤特异性生长因子(TSGF)水平均显著降低,且IMRT组低于3D-CRT组(P0.05)。结论:IMRT与3D-CRT对于晚期非小细胞肺癌患者的临床疗效相当,但IMRT药物毒副反应少、放射剂量低,可能通过控制肿瘤来降低肿瘤标志物水平。     

血清CEA、CA211水平与晚期非小细胞肺癌靶向治疗患者疗效、预后的关系及其诊断价值分析

目的:探讨血清癌胚抗原(CEA)、细胞角蛋白19片段(CA211)水平与晚期非小细胞肺癌(NSCLC)靶向治疗患者疗效、预后的关系,并分析其对治疗有效性的诊断价值。方法:选取2013年6月到2017年8月期间在广西医科大学附属肿瘤医院接受治疗的晚期NSCLC患者90例,所有患者均采用盐酸厄洛替尼片进行治疗。记录所有患者治疗后的临床疗效,根据治疗效果将患者分为有效组和无效组,比较不同治疗效果患者的血清CEA、CA211水平,分析血清CEA、CA211水平与患者无进展生存期(PFS)的关系,并分析患者血清CEA、CA211单独检测和联合检测对治疗有效性的诊断价值。结果:靶向治疗后,90例晚期NSCLC患者的总有效率为44.44%。治疗后,有效组的血清CEA、CA211水平明显低于治疗前,无效组的血清CEA、CA211水平明显高于治疗前(P0.05),有效组的血清CEA、CA211水平明显低于无效组(P0.05)。CEA15 ng/mL的患者PFS明显短于CEA15 ng/mL的患者(P0.05),CA211≥5 ng/mL的患者PFS明显短于CA2115 ng/mL的患者(P0.05),血清CEA、CA211联合检测的敏感度高于CEA、CA211单独检测(P0.05)。结论:CEA和CA211水平与晚期NSCLC靶向治疗患者疗效、预后有关,且血清CEA、CA211联合检测可提高靶向治疗效果评价的敏感度。     

DC-CIK细胞免疫治疗晚期结直肠癌患者的远期疗效及其影响因素分析

目的:探讨树突状细胞(DC)联合细胞因子诱导的杀伤(CIK)细胞免疫治疗晚期结直肠癌(CRC)患者的远期疗效及其影响因素分析。方法:收集我院2011年1月至2014年1月收治的112例晚期结直肠癌患者,依据是否接受DC-CIK细胞免疫治疗将患者分为对照组(n=47)和观察组(n=65),分别给予一般化疗方案治疗和化疗联合DC-CIK细胞免疫方案治疗,比较两组患者治疗前后血清肿瘤标志物癌胚抗原(CEA)、淋巴细胞亚群,治疗有效率(RR)、疾病控制率(DCR)、无进展生存期(PFS)和安全性改变,并分析影响疗效的危险因素。结果:两组治疗后CEA水平均显著低于治疗前(P0.05),治疗后对照组CD3+T细胞、CD4+T细胞、CD8+T细胞和NK细胞均显著减少(P0.05),观察组治疗后CD3+T细胞和CD8+T细胞数量显著高于治疗前和同期对照组(均P0.05);对照组RR、DCR和PFS分别为44.68%、65.96%、6.5个月,观察组治疗对应指标分别为46.15%、86.15%、9个月,观察组DCR和FPS均显著高于对照组(P0.05);多因素分析发现TNM分期达到Ⅳ级(P=0.023)和年龄超过60岁(P=0.006)是影响疗效的独立危险因素。结论:DC-CIK细胞免疫治疗晚期结直肠癌安全可靠,能显著改善患者免疫功能控制肿瘤进展,延长生存期,提高生存质量,值得临床推广。     

索拉非尼联合化疗栓塞治疗晚期原发性肝癌的疗效分析

目的:原发性肝癌(Primary hepatocellular carcinoma,PHC)是最常见的消化系统恶性肿瘤之一,严重威胁人类的健康。目前,治疗晚期肝癌的首选方法是肝动脉化疗栓塞(Transcatheter arterial chemoembolization,TACE),配合抗癌药物使用,治疗效果明显。索拉非尼因具有抑制肿瘤生长的作用而被越来越广泛的用于治疗肝癌。本研究针对索拉非尼的靶向性,探讨该药与化疗栓塞联合治疗晚期原发性肝癌的疗效,旨在为肝癌的临床治疗提供可参考的依据。方法:选取我院2008年10月-2012年6月收治的晚期原发性肝癌患者96例,随机分为对照组和观察组,每组各48例。对照组患者采用肝动脉化疗栓塞单独治疗,观察组患者采用索拉非尼联合化疗栓塞治疗。比较两组患者的客观有效率、临床获益率、治疗一年生存率、两年以上生存率及甲胎蛋白(AFP)水平的变化情况。结果:观察组患者的客观有效率为52.1%,临床获益率为89.6%,均高于对照组患者的对应值33.3%和47.9%,差异有统计学意义(P0.05);观察组患者一年生存率为89.6%,两年生存率为72.9%,均高于对照组患者的对应值58.3%和35.4%,差异显著(P0.05);两组患者治疗后的AFP水平均比治疗前降低,观察组患者AFP水平的改善情况显著优于对照组,差异具有统计学意义(P0.05)。结论:索拉非尼联合化疗栓塞治疗晚期原发性肝癌具有明显的效果,且安全性高,值得临床推广使用。     

埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌的疗效及对生活质量和血清肿瘤标志物的影响

目的:观察表皮生长因子受体(EGFR)突变型晚期非小细胞肺癌(NSCLC)经化疗联合埃克替尼治疗后的临床效果。方法:122例研究对象均为我院于2015年3月~2019年3月期间收治的晚期NSCLC患者且为EGFR突变型。采用随机数字表法将患者分为对照组(单药埃克替尼靶向药物治疗)和实验组(埃克替尼联合化疗),各61例。观察两组疗效、生活质量、血清肿瘤标志物、毒副反应的变化,比较两组患者的无进展生存期(PFS)和总生存期(OS)。结果:实验组治疗后的客观缓解率、疾病控制率均高于对照组(P<0.05)。实验组治疗后整体生活质量和健康状况总得分高于对照组,功能及症状总得分低于对照组(P<0.05)。实验组治疗后癌胚抗原(CEA)、癌抗原125(CA125)与角蛋白19片段(CYFRA21-1)低于对照组(P<0.05)。实验组毒副反应总发生率高于对照组(P<0.05)。两组间PFS、OS生存率比较均有统计学差异(P<0.05)。结论:埃克替尼联合化疗治疗EGFR突变型晚期NSCLC患者疗效较好,可有效阻止疾病进展,提高患者生活质量,改善患者预后。     

厄洛替尼治疗19例晚期非小细胞肺癌的临床观察

目的:观察厄洛替尼(Erlotinib)治疗晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)的临床疗效及毒副反应。方法:我科于2011年2月-2014年2月收治19例晚期NSCLC患者,给予口服Erlotinib 150 mg/天进行分子靶向治疗,直至疾病进展或出现不可耐受的毒副反应,对其临床疗效及毒副反应进行观察。结果:19例患者均可进行疗效评估,客观缓解率为21.1%(4/19),疾病控制率为63.2%(12/19)。中位无进展生存期为8个月(95%CI 5.5-10.8),中位生存期为17个月(95%CI 11.3-22.7),1年生存率为73.7%(14/19),2年生存率为45.5%(5/11)。分析发现患者的性别、年龄、病理类型、吸烟史、手术史、放疗史与客观缓解率、疾病控制率无明显相关性(P0.05),仅化疗史与疾病控制率相关(P=0.02)。Erlotinib的副反应较轻,无患者因毒副反应而减量或停药。结论:Erlotinib治疗晚期NSCLC的疗效及安全性良好,可作为不能耐受放化疗或放化疗失败的晚期NSCLC患者的治疗选择。     

吉非替尼联合GP化疗方案治疗晚期非小细胞肺癌的效果及对血清CEA、SCC、NSE、CYFRA21-1水平的影响

目的:研究吉非替尼联合吉西他滨和顺铂(GP)化疗方案治疗晚期非小细胞肺癌的效果及对血清癌胚抗原(Carcinoembbryonic antigen,CEA)、鳞状细胞癌相关抗原(Squamous cell carcinoma,SCC)、神经元特异烯醇化酶(Neuron-specific enolase,NSE)、细胞角蛋白19片段(Cytokeratin-19-fragment,CYFRA21-1)水平的影响。方法:选取2016年6月～2018年6月我院收治的晚期非小细胞肺癌患者110例,采用随机数字表法将患者分为两组,每组55例。对照组患者给予GP化疗方案,观察组在对照组的基础上给予吉非替尼。比较两组患者的临床治疗效果,治疗前后血清肿瘤标志物水平和生活质量的变化以及不良反应发生情况。结果:治疗后,观察组疾病控制率为86.67%,对照组为74.55%,观察组显著高于对照组(P0.05);两组治疗后血清CEA、SCC、NSE和CYFRA21-1水平均较治疗前显著下降,且观察组以上指标均显著低于对照(P0.05);两组治疗后FACT-L各项评分包括躯体状况、社会家庭状况、情感状况、肺癌特异性模块和功能状况评分均较治疗前显著升高,且观察组以上指标均显著高于对照(P0.05)。治疗期间,观察组患者白细胞减少、血小板减少、肝肾功能异常的发生率显著低于对照组(P0.05),两组贫血、恶心呕吐的发生率比较无统计学差异(P0.05)。结论:与GP化疗方案相比,吉非替尼联合GP化疗方案可更显著提高晚期非小细胞肺癌患者的治疗效果,改善其生活质量,且安全性较高,可能与其降低血清CEA、SCC、NSE和CYFRA21-1水平有关。     

埃克替尼治疗晚期非小细胞肺癌的疗效及对患者血清相关指标水平的影响

目的:分析埃克替尼对晚期非小细胞肺癌的治疗效果及对血清指标的影响。方法:将86例晚期非小细胞肺癌患者按抽签法分成对照组与观察组,各43例。对照组采用多西他赛治疗,观察组采用埃克替尼治疗。观察并比较两组患者治疗前后血清细胞角蛋白21-1(Cyfre21-1)、鳞状细胞癌抗原(SCCA)、血管内皮生长因子(VEDF)、自然杀伤(NK)细胞、CD4~+、CD8~+、CD4~+/CD8~+,白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-2(MMP-2)及基质金属蛋白酶-9(MMP-9)水平、临床疗效以及安全性。结果:观察组疾病控制率高于对照组,差异具有统计学意义(P0.05)。治疗后,两组患者血清Cyfre21-1、SCCA、CD8~+、LI-8、TNF-α、MMP-2及MMP-9均低于治疗前,且观察组低于对照组,,差异具有统计学意义(P0.05);治疗后,两组患者血清VEGF水平均降低,且观察组低于对照组,差异具有统计学意义(P0.05);治疗后,两组患者血清NK、CD4~+及CD4~+/CD8~+均高于治疗前,且观察组高于对照组,差异具有统计学意义(P0.05);观察组不良反应发生率低于对照组,差异具有统计学意义(P0.05)。结论:埃克替尼对晚期非小细胞肺癌的临床效果肯定,可下调血清VEGF表达。     

Anthropology and genetics of the caucasus peoples and the problem of the origin of the caucasoids

The electrophoretical polymorphisms of some blood proteins were studied in the Talysh population of Pirasora situated in South-East Azerbaidjan. We calculated the gene frequencies of these polymorphisms and determined the genetic distances between the Talyshes and some Iranian populations of North, Central and South Iran, Afghans, and three populations of Azerbaijan. The Talyshes are very close to Iranians of Shiraz, whereas they are distant from the Azerbaijanians. Anthropological investigations showed that the Caucasoids and Mongoloids lived in the Aragvi Basin since the Eneolithic period. This was stated by Alexeev (1974), who emphasized the mixture of the Caucasus populations from ancient times on. We calculated the genetic distances between the Caucasus populations and numerous populations of other geographic regions, considering 28 alleles of 12 loci of blood group, serum protein and red cell enzyme polymorphisms and constructed the dendrogram of these populations. The position of the Caucasus populations in the dendrogram corresponds on principle to the earlier anthropological observations. The clustering of the Caucasoid populations corresponds completely with anthropological and historical data, and supports our earlier hypothesis (Nazarova 1999) concerning the differentiation of Caucasoids, Northern Mongoloids and Amerinds from the populations, which inhabitated Asia in palaeolithic times.     

Serology and systematics of the Ebenales and the Theales

The systematic position ofthe Ebenaceae, Sapotaceae, Styracaceae, Ochnaceae, Stachyuraceae, Dipterocarpaceae, Clusiaceae and Hypericaceae has been investigated using serological comparisons of sets of antigenic determinants. The results show that the Sytracaceae and Sapotaceae are undoubtedly more closely associated with the Actinidiaeceae and Theaceae, respectively, than with each other. We found no corresponding determinants betnween antigen systems from the Ebenaceae and systems from any other family whose relations to this family have been proposed. As discovered previously, investigations of antigen systems from the Ochnaceae, Dipterocarpaceae, Stachyuraceae, Clusiaceae and Hypericaceae are against the idea of a natural order “Theales” in which these families, or at least some of them, are combined with the Theaceae and Actinidiaceae. This paper completes our previous investigations which largely support a superorder Ericanae sensu Ehrendorfer and Takhtajan. We propose to include the Actinidiaceae and Theaceae in this superorder, assigning them a central position laong with the Sapotaceae and Sytracaeae on one side and the Primulales and Ericales on the other. Another most interesting finding is that there are corresponding determinants between antigen systems from the members of the Ericanae and representatives of the Polemoniaceae and Loasaceae.     

人类基因组及后基因组研究进展及其应用与开发研究现状

人类对自身基因组的研究,随着人类基因组工作草图的绘制完成和对基因功能研究的深入已加快进入了实质性、关键性的开发利用阶段。本文概述了人类基因组及后基因组的研究进展及依此开展基因治疗及基因（组）药物研制等应用开发研究的现状。     

On the structure and dynamics of the complex of the nucleosome and the linker histone

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.     

Kinematics and dynamics of the temporomandibular joint and of the movements of the mandible

In order to analyze the complicated movements of the mandible as the open-closing movement and the protrusio are, it is useful to evaluate the basic kinematic principles and reduce them to simple technical constructions. Both the open-closing movement and the protrusio could be reduced to 4-bar links, which were used to simulate the movements with help of a computer. Besides, the polodes and the curves of points in the muscular attachments could be constructed. The 2 entirely different 4-bar links have 3 things in common: The resting system - cranium, the moving system - mandibula, and 1 of the 2 arms connecting these 2 systems - the ligamentum laterale. As this ligament is taut during movements it can be considered a "guiding ligament" representing 1 of the 3 determining components of the mandibular movements. The other of the 2 arms has no anatomical equivalent; this arm, however, is "replaced" by the 2 other determining components of the mandibular movements: the joint and the muscles. The curves, which the Caput mandibulae describes, are practically identical for the open-closing movement and the protrusio despite of the different 4-bar links and these curves exactly correspond to the Discus articularis, taut by the upper part of the M. pterygoideus lateralis. The muscles do not only just move the mandibula, but they are also the component, which can choose between the different mandibular movements. By means of the curves, which points in the muscular attachments describe, the function of the masticatory muscles could be analyzed exactly.     

Biophysics and Structure of the Patch and the Gigaseal

Interpreting channel behavior in patches requires an understanding of patch structure and dynamics, especially in studies of mechanosensitive channels. High resolution optical studies show that patch formation occurs via blebbing that disrupts normal membrane structure and redistributes in situ components including ion channels. There is a 1-2 μm region of the seal below the patch where proteins are excluded and this may consist of extracted lipids that form the gigaseal. Patch domes often have complex geometries with inhomogeneous stresses due to the membrane-glass adhesion energy (E_a), cytoskeletal forces, and possible lipid subdomains. The resting tension in the patch dome ranges from 1-4 mN/m, a significant fraction of the lytic tension of a bilayer (∼10 mN/m). Thus, all patch experiments are conducted under substantial, and uneven, resting tension that may alter the kinetics of many channels. E_a seems dominated by van der Waals attraction overlaid with a normally repulsive Coulombic force. High ionic strength pipette saline increased E_a and, surprisingly, increased cytoskeletal rigidity in cell-attached patches. Low pH pipette saline also increased E_a and reduced the seal selectivity for cations, presumably by neutralizing the membrane surface charge. The seal is a negatively charged, cation selective, space with a resistance of ∼7 gigohm/μm in 100 mM KCl, and the high resistivity of the space may result from the presence of high viscosity glycoproteins. Patches creep up the pipette over time with voltage independent and voltage dependent components. Voltage-independent creep is expected from the capillary attraction of E_a and the flow of fresh lipids from the cell. Voltage-dependent creep seems to arise from electroosmosis in the seal. Neutralization of negative charges on the seal membrane with low pH decreased the creep rate and reversed the direction of creep at positive pipette potentials.     

The efficacy of ropivacaine and bupivacaine in the caesarean section and the effect on the vital signs and the hemodynamics of the lying-in women

ObjectiveTo investigate the efficacy of ropivacaine and bupivacaine in caesarean section and vital signs and the hemodynamics of the lying-in women.MethodsA total of 480 lying-in women who were admitted to this hospital for treatment between December 2017 and June 2018 were enrolled into this study as the subjects, which were divided into the experiment group and the control group, with 240 subjects in each group. In the experiment group, subjects received the local anesthesia by infusion of 1.5 mL ropivacaine (0.75%), while those in the control group also took the local anesthesia by infusion of 1.5 mL bupivacaine (0.75%). Thereafter, we observed the differences in the anesthetic efficiency, vital signs and hemodynamics of the lying-in women between two groups.ResultsThe excellent and good rates of the anesthesia in two groups were 92.1% and 87.9%, showing no obvious difference; in the experiment group, the average arterial pressures and systolic pressures at 5 min and 10 min after combined spinal and epidural analgesia (CSEA) were all elevated when comparing to the control group (all P < 0.05); in the experiment group, the onset time was obviously extended, while duration of sensory and motor block and the duration of motor block were all shorter than those in the control group (all P < 0.05). During anesthesia, the incidence rate of the adverse reactions in the control group was 2.50%, significantly higher than 0.83% in the experiment group (P < 0.05).ConclusionDespite that ropivacaine and bupivacaine are efficient in anesthesia in the CSEA in the caesarean section, ropivacaine is more recommended for little influence on the hemodynamics, shorter duration of sensory block and motor block and low incidence rate of adverse reactions, which are conducive to the recovery and also safe to the patients.