吉西他滨联合奥沙利铂方案治疗晚期胆囊癌与胆管癌临床观察

目的观察吉西他滨联合奥沙利铂方案治疗晚期胆囊癌和胆管癌临床疗效和毒副作用。方法16例晚期胆囊癌和胆管癌患者,应用吉西他滨联合奥沙利铂方案化疗,即吉西他滨1000mg／m^2,第1、第8天应用,奥沙利铂100mg／m^2,第1天。每21天重复,直至出现不可耐受的副作用或肿瘤进展。结果16例均可以进行疗效评价,CR1例,PR6例,SD6例,PD3例,总有效率43．7％。中位生存期为12．8个月。不良反应主要为骨髓抑制、外周神经炎等。结论吉西他滨联合奥沙利铂方案治疗晚期胆囊癌和胆管癌近期疗效较好,不良反应有可以耐受性。可作为晚期胆囊癌和胆管癌的治疗选择。     

多西他赛联合奥沙利铂在晚期胃癌治疗中的临床效果分析

目的探索多西他赛联合奥沙利铂在高原地区晚期胃癌治疗中的临床应用价值。方法75例晚期胃癌,随机抽样38例进入研究组,其余37例为对照组,分别给予DO方案（多西他赛联合奥沙利铂）和DCF方案（多西他赛＋氟尿嘧啶＋顺铂）化疗。结果DO组和DCF组的有效率分别为44．73％和40．54％,两组间差异无统计学意义（P〉0．05）。DO组,隘床受益反应有效率81．6％,DCF组组临床受益反应有效率75．7％。观察组和对照组不良反应情况中骨髓抑制,腹泻,脱发,关节酸痛及口腔黏膜炎的发生率差异无统计学意义,但DO方案胃肠道反应较DCF方案轻,而神经毒性较DCF方案明显。结论D0方案治疗晚期胃癌疗效确切,胃肠道反应等不良反应轻,值得临床中推广。。     

ACEI与ARB联合治疗糖尿病肾病疗效观察

目的：研究血管紧张素转换酶抑制药（ACEI）和血管紧张素受体拮抗药（ARB）对2型糖尿病肾病患者肾功能的保护作用。方法：选择有肾功能损害的糖尿病病人90例,在常规糖尿病治疗的同时,随机分成3组,分别给予ACEI、ARB、ACEI合并ARB治疗,观察治疗前后24h尿蛋白的变化。结果：3组患者治疗后尿蛋白排泄均减少,差别有统计学意义（P〈0．05）,而联合治疗组与其他两组相比,差别有统计学意义（P〈0．05）。结论：ACEI和ARB联用能更好地起到肾脏保护作用。     

国产与进口奥沙利铂在直肠癌术后化疗中的安全性与有效性的比较研究

目的：探讨国产与进口奥沙利铂在直肠癌术后化疗中的安全性与有效性,指导临床用药。方法：对同期收治的TNMⅡ和Ⅲ期直肠癌患者共97例,随机分为国产奥沙利铂（奥沙利铂注射液）组52例,和进口奥沙利铂（乐沙定）组45例,进行术后辅助化疗,采用FOLFOX4方案,观察、记录患者的不良反应及术后局部复发、远处转移及生存情况,进行统计学分析。结果：两组患者化疗不良反应的差异无显著性意义（P〉0.05）,3年后的局部复发及存活率存在一定的差异。结论：国产奥沙利铂使用仍然是安全、有效的,其3年生存率较高;对有经济条件的患者,可以考虑使用进口奥沙利铂,对患者整体术后治疗是有益的。     

注射用奥沙利铂纳米结构脂质载体冻干制剂的工艺优选

目的考察注射用奥沙利铂纳米结构脂质载体（OP NLC）冻干粉末处方及工艺。方法通过单因素实验优选冻干制剂的处方工艺,并评价其制剂学性质。结果以5%甘露醇溶液作为冻干保护剂,确定最终的冻干工艺。冻干后制剂粒径（124±16） nm,Zeta电位－10.8 mV,包封率67.3%,与冻干前［粒径（115±17） nm,Zeta电位－16.0 mV,包封率72.6%］相比,无明显变化。结论在优选的冻干工艺条件下可制得稳定的奥沙利铂纳米结构脂质载体冻干制剂。     

高压氧复合星状神经节阻滞治疗突发性耳聋的疗效分析

目的 观察高压氧复合星状神经节阻滞治疗突发性耳聋的疗效。方法 突发性耳聋患者84例,随机分为3组,每组28例:高压氧组(A组)采用高压氧治疗,压力为0.2MPa(2ATA),纯氧加压80分钟,每天1次,10次为1个疗程;星状神经节阻滞组(B组)以1%利多卡因10mL加维生素B12 500μg,行星状神经节阻滞(双侧者交替阻滞),1次/天,连续10天为1疗程;C组使用A组和B组两种方法联合治疗,观察治疗效果及不良反应。结果 三组病例治疗后耳聋症状均有改善,A组痊愈率为21.4%,有效率为64.3%;B组痊愈率为28.6%,有效率为75%;C组痊愈率为60.8%,有效率为89.3%。与A组、B组相比较,C组痊愈率和有效率显著提高(P<0.05或P<0.01)。结论 高压氧复合星状神经节阻滞治疗突发性耳聋的疗效令人满意,值得推广应用。     

Efficacy of Aerosolized Celecoxib Encapsulated Nanostructured Lipid Carrier in Non-small Cell Lung Cancer in Combination with Docetaxel

Purpose

Evaluation of in-vivo anticancer activity of aerosolized Celecoxib encapsulated Nanolipidcarriers (Cxb-NLC) as a single therapeutic agent and combined with intravenously administered Docetaxel (Doc) against non-small cell lung cancer.

Methods

Cxb-NLC were prepared by high-pressure homogenization and were characterized for its physicochemical characteristics. Metastatic A549 tumor model in Nu/Nu mice was used to evaluate response of aerosolized Cxb-NLC & Doc. Isolated lung tumor samples were analyzed for: a) DNA fragmentation and cleaved caspase-3 by immunohistochemistry, b) apoptotic and angiogenic protein markers by western blot, c) global proteomic alterations by an isobaric labeling quantitative proteomic method and d) toxicity studies of NLC.

Results

The particle size of Cxb-NLC was 217?±?20 nm, while entrapment efficiency was more than 90%. Cxb-NLC and Doc alone and in combination showed 25?±?4%, 37?±?5%, and 67?±?4% reduction in tumor size respectively compared to control. Proteomic analysis with combination treatment further revealed significantly decreased expression of multiple pro-survival and pro-metastasis proteins as well as tumor invasion markers and the expression of S100 family proteins, such as S100A6 and S100P were decreased by 2.5 and 1.6 fold.

Conclusions

Combination therapy with Cxb-NLC and Doc showed significant reduction in tumor growth which was further confirmed by proteomic analysis.     

Enhanced oral paclitaxel absorption with vitamin E-TPGS: Effect on solubility and permeability in vitro, in situ and in vivo

Solubility and permeability being important determinants of oral drug absorption, this study was aimed to investigate the effect of d--tocopheryl polyethylene glycol 1000 succinate (TPGS) on the solubility and intestinal permeability of paclitaxel in vitro, in situ and in vivo, in order to estimate the absorption enhancement ability of TPGS. Aqueous solubility of paclitaxel is significantly enhanced by TPGS, where a linear increase was demonstrated above a TPGS concentration of 0.1 mg/ml. Paclitaxel demonstrated asymmetric transport across rat ileum with significantly greater (26-fold) basolateral-to-apical (B–A) permeability than that in apical-to-basolateral (A–B) direction. Presence of P-glycoprotein (P-gp) inhibitor, verapamil (200 μM), diminished asymmetric transport of paclitaxel suggesting the role of P-gp-mediated efflux. TPGS showed a concentration-dependent increase in A–B permeability and decreased B–A permeability. The maximum efflux inhibition activity was found at a minimum TPGS concentration of 0.1 mg/ml, however, further increase in TPGS concentration resulted in decreased A–B permeability with no change in B–A permeability. Thus, the maximum paclitaxel permeability attained with 0.1 mg/ml TPGS was attributed to the interplay between TPGS concentration dependent P-gp inhibition activity and miceller formation. In situ permeability studies in rats also demonstrated the role of efflux in limiting permeability of paclitaxel and inhibitory efficiency of TPGS. The plasma concentration of [¹⁴C]paclitaxel following oral administration (25 mg/kg) was significantly increased by coadministration of TPGS at a dose of 50 mg/kg in rats. Bioavailability is enhanced about 4.2- and 6.3-fold when [¹⁴C]paclitaxel was administrated with verapamil (25 mg/kg) and TPGS, respectively, as compared to [¹⁴C]paclitaxel administered alone. The effect of verapamil on oral bioavailability of [¹⁴C]paclitaxel was limited relative to the TPGS, consistent with the in vitro solubility and permeability enhancement ability of TPGS. In conclusion, the current data suggests that the coadministration of TPGS may improve the bioavailability of BCS class II–IV drugs with low solubility and/or less permeable as a result of significant P-gp-mediated efflux.     

促骨形成和抗骨吸收剂联合治疗骨转移癌效果分析

目的：评价化疗、促骨形成剂和抗骨吸收剂联合治疗骨转移癌的效果。方法：以A（化疗＋抗骨吸收剂＋促骨形成剂）和B（化疗＋抗骨吸收剂）2种方案分组治疗71例骨转移癌,对照分析结果,结果：（1）在减轻疼痛、促进骨修复方面A方案优于B方案。（2）治疗中未出现严重不良反应。结论：化疗联合促骨形成和抗骨吸收剂治疗骨转移癌效果确切,促骨形成剂不仅适用于骨质疏松患者,也可能成为骨转移癌治疗中的有效辅助药物     

三联疗法治疗老年膝骨关节炎的近期疗效观察

目的探讨三联疗法(透明质酸钠 得宝松 超短波)对于缓解老年膝骨关节炎的疼痛症状及改善其活动功能的效果。方法选择60例老年膝骨关节炎患者,进行关节腔内注射透明质酸钠2ml/次,每周1次;关节周围采用得宝松7mg VitB120.5mg 2%利多卡因5ml进行痛点阻滞,每2周1次;超短波疗法采用每日1次,每次10min。所有治疗方案均持续1个月。分别观察治疗前后疼痛评分及关节活动能力评分。结果治疗膝关节疼痛症状明显缓解,疼痛评分明显降低;关节活动能力评分关节明显降低,活动功能得到显著改善,治疗有效率达96.7%。无任何不良反应的发生。结论应用三联疗法治疗老年膝骨关节炎疗效显著,无严重的不良反应,是一种有效安全的方法。     

奥沙利铂加氟尿嘧啶治疗晚期食管癌的临床观察

目的探讨奥沙利铂加氟尿嘧啶在晚期食管癌中的治疗价值。方法将我院收治的60例晚期食管癌患者按照治疗方法的不同分为观察组和对照组,对照组给予顺铂、亚叶酸钙联合氟尿嘧啶治疗,观察组给予奥沙利铂、亚叶酸钙联合氟尿嘧啶,比较两组患者的近期疗效、不良反应以及生活质量。结果观察组的总有效率为43.3%,对照组的为40.0%,无统计学意义(P>0.05)。两组的中位进展时间也无统计学意义(P>0.05)。但观察组在恶心、呕吐、腹泻等不良反应的发生率显著低于对照组,生存质量显著高于对照组(P<0.05)。结论奥沙利铂加氟尿嘧啶治疗晚期食管癌疗效满意,不良反应较少,是较为安全有效的化疗方案。     

Enhanced Oral Bioavailability of Paclitaxel Formulated in Vitamin E-TPGS Emulsified Nanoparticles of Biodegradable Polymers: In Vitro and In Vivo Studies

This work evaluates the effects of paclitaxel loaded polymeric nanoparticles (NPs) composed of poly(D,L-lactic-co-glycolic acid) (PLGA) with vitamin E TPGS as emulsifier for oral chemotherapy. NPs prepared by a modified solvent extraction/evaporation technique were observed in spherical shape of 200-300 nm diameter with a high drug encapsulation efficiency (EE) of 80.9%. The TPGS-emulsified PLGA NPs formulation of paclitaxel was found of great advantages over that of Taxol®. The in vitro viability experiment showed that the NP formulation could be 1.28,1.38,1.12 times more effective than Taxol® after 24, 48, 72 h incubation with MCF-7 human breast cancer cell line at 2.5 μg/mL paclitaxel concentration. In vivo evaluation confirmed the advantages of the TPGS-emulsified PLGA NP formulation versus Taxol® in promoting oral bioavailability of paclitaxel. Such a NP formulation achieved more than 10 times higher oral bioavailability than Taxol®, which resulted 9.74-fold higher therapeutic effect and 12.56-fold longer sustainable therapeutic time than Taxol®. The present proof-of-concept experimental data proved that the formulation of vitamin E TPGS emulsified PLGA NPs is a promising approach for paclitaxel oral administration. Oral chemotherapy by NPs formulation is feasible. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3552-3560, 2010     

Vit C、Vit E对造血干细胞移植患者血浆谷胱甘肽抗氧化体系的影响

目的 探讨VitC、VitE对造血干细胞移植(HSCT)患者血浆谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-Px)影响.方法 60例造血干细胞移植患者均分为两组,实验组移植前给予Vit C(300 mg/d)和Vit E(600 mg/d)口服;对照组不予补充.测定移植前后两组血浆GSH、GSH-Px以及丙二醛(MDA).结果 移植前两组GSH显著高于正常值(P<0.01),GSH-Px低于正常值(P<0.05).移植后两组GSH、GSH-Px及MDA均有差异(P<0.05和P<0.01).结论 移植前补充抗氧化性维生素可以增强患者血浆GSH-Px活力,降低GSH,减少MDA,有效缓解移植前预处理造成的高氧化胁迫.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的疗效观察

目的探讨奥沙利铂、5-氟脲嘧啶和亚叶酸钙联合治疗晚期结直肠癌的疗效及不良反应。方法 40例晚期结直肠癌患者均采用奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗,治疗方案为:奥沙利铂130mg/m2静脉滴注4h,第1天;亚叶酸钙200mg/m2静脉滴注2h,第1～5天(在静脉滴注5-氟尿嘧啶之前),5-氟尿嘧啶400mg/m2静脉滴注4～6 h,平均用药4周期,2周期后进行疗效评价。结果 40例晚期结直肠癌患者中,完全缓解(CR)4例(10%),部分缓解(PR)18例(45%),稳定(SD)10例(25%),进展(PD)8例(20%),总有效率(ORR)为55%。不良反应为厌食疲乏、皮肤色素沉着、神经毒性、手足综合症、腹泻、恶心呕吐、肝功损害、白细胞下降,多数患者能耐受。结论奥沙利铂联合5-氟尿嘧啶和亚叶酸钙治疗晚期结直肠癌的疗效肯定,毒副反应小,患者能耐受,值得推广。     

Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development

Botulinum neurotoxins (BoNTs) show increasing therapeutic applications ranging from treatment of locally paralyzed muscles to cosmetic benefits. At first, in the 1970s, BoNT was used for the treatment of strabismus, however, nowadays, BoNT has multiple medical applications including the treatment of muscle hyperactivity such as strabismus, dystonia, movement disorders, hemifacial spasm, essential tremor, tics, cervical dystonia, cerebral palsy, as well as secretory disorders (hyperhidrosis, sialorrhea) and pain syndromes such as chronic migraine. This review summarizes current knowledge related to engineering of botulinum toxins, with particular emphasis on their potential therapeutic applications for pain management and for retargeting to non-neuronal tissues. Advances in molecular biology have resulted in generating modified BoNTs with the potential to act in a variety of disorders, however, in addition to the modifications of well characterized toxinotypes, the diversity of the wild type BoNT toxinotypes or subtypes, provides the basis for innovative BoNT-based therapeutics and research tools. This expanding BoNT superfamily forms the foundation for new toxins candidates in a wider range of therapeutic options.     

HPLC法测定多维铁口服溶液中维生素B_1、维生素B_2的含量

目的:建立以高效液相色谱法测定多维铁口服溶液中维生素B1、维生素B2含量的方法。方法:色谱柱为C18,流动相为离子对溶液(含1·5mmol·L-1戊烷磺酸钠和3·4mmol·L-1庚烷磺酸钠的0·24%三乙胺溶液,用冰醋酸调节pH值至3·0)-甲醇(80:20),检测波长为254nm,流速为1·0mL·min-1,进样量为10μL。结果:维生素B1、维生素B2检测浓度的线性范围分别为4·81～24·6(r=0·9991)、6·22～31·7μg·mL-1(r=0·9998);平均回收率分别为103·3%(RSD=0·5%)、99·5%(RSD=0·7%)。结论:本方法简便准确、灵敏度高、结果可靠,可用于该制剂中维生素B1、维生素B2的含量测定。     

锌制剂治疗头颈部肿瘤放射性口腔黏膜炎疗效的Meta分析

目的:系统评价锌制剂治疗头颈部肿瘤放射性口腔黏膜炎的疗效,为临床治疗提供循证参考。方法:计算机检索PubMed、Medline、Embase、Cochrane图书馆、中国期刊全文数据库、维普网、万方数据,检索时限均为建库起至2018年12月,收集在常规治疗或空白对照(对照组)的基础上加用锌制剂(试验组)治疗头颈部肿瘤放射性口腔黏膜炎疗效的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价后,采用Rev Man 5.3统计软件对给药后2周放射性口腔黏膜炎发生率、放射性口腔黏膜炎总发生率、严重放射性口腔黏膜炎发生率进行Meta分析。结果:共纳入8项RCT,合计550例患者。Meta分析结果显示,两组患者2周放射性口腔黏膜炎发生率[OR=0.55,95%CI(0.26,1.17),P=0.12]、放射性口腔黏膜炎总发生率[OR=0.59,95%CI(0.08,4.39),P=0.60]及严重放射性口腔黏膜炎发生率[OR=0.58,95%CI(0.23,1.47),P=0.25]比较差异均无统计学意义。结论:在常规治疗或空白对照的基础上加用锌制剂不能降低头颈部肿瘤放射性口腔黏膜炎发生率及控制疾病发展。     

瑞舒伐他汀与阿托伐他汀对冠心病患者血脂、动脉粥样硬化程度和血管内皮舒张功能的疗效对比

目的:对比瑞舒伐他汀与阿托伐他汀对冠心病患者血脂、动脉粥样硬化程度和血管内皮舒张功能的疗效。方法:选择2014年1月-2015年12月于我院心血管内科住院的冠心病患者150例,按照抽签法分为瑞舒伐他汀组(72例)和阿托伐他汀组(78例)。所有患者均调整生活习惯,给予抗血小板和调整血压药物等基础治疗。同时,瑞舒伐他汀组患者给予瑞舒伐他汀钙片10 mg,po,每晚1次;阿托伐他汀组患者给予阿托伐他汀钙片20 mg,po,每晚1次。两组患者均治疗6个月。比较治疗前后两组患者的血脂指标[总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]水平、颈动脉内-中膜厚度(IMT)、颈动脉斑块积分(Crouse积分)、冠状动脉狭窄程度评分(Gensini评分)和肱动脉内径变化百分率(D),记录不良反应发生情况。结果:治疗前,两组患者上述各指标比较,差异均无统计学意义(P>0.05)。治疗后,两组患者的TC、TG、LDL-C、IMT、Crouse积分和Gensini评分均较治疗前显著下降,HDL-C和D值较治疗前显著上升,且瑞舒伐他汀组患者的TC、TG、LDL-C、Crouse积分和Gensini评分均显著低于阿托伐他汀组,D值显著高于阿托伐他汀组,差异均有统计学意义(P<0.05);但两组患者的HDL-C和IMT比较,差异均无统计学意义(P<0.05)。治疗过程中,瑞舒伐他汀组有1例患者出现头晕,后自行缓解;两组各有4例患者出现转氨酶轻度升高,经护肝治疗后恢复正常。结论:瑞舒伐他汀在降低冠心病患者血脂、改善AS和血管内皮舒张功能方面较阿托伐他汀疗效更显著,且安全性较高。     

美托洛尔与他汀类药联合治疗心肌梗死的疗效观察

目的:探讨美托洛尔(倍他乐克)与他汀类药联合治疗心肌梗死患者的临床疗效。方法:将2012年8月—2013年8月来我院治疗的126例心肌梗死患者以随机抽样法分为观察组及对照组各63例,对照组给予硝酸酯类药及阿司匹林等常规治疗,观察组在对照组的基础上给予美托洛尔与他汀类药联合治疗,比较2组患者的临床治疗总有效率、心率(HR)、二尖瓣舒张早晚期充盈流速比(E/A)、胆固醇(TC)、左心房内径(LVADD)。结果:观察组患者临床总有效率为92.06%(58/63),对照组为71.43%(45/63),观察组高于对照组,差异有统计学意义(P<0.05)。观察组患者的HR、TC、LVADD低于对照组,E/A高于对照组,差异有统计学意义(P<0.05)。结论:美托洛尔与他汀类药联合治疗心肌梗死临床疗效显著,能够重塑心功能,可以在临床推广应用。