����ù��-�ȵ�������������1�ںϵ��׵Ĺ������俹��Сϸ���ΰ������о�

??OBJECTIVE To construct a novel fusion protein contained insulin-like growth factor 1 (IGF-1) and lidamycin (LDM) and evaluate its antitumor activity on non-small cell lung cancer (NSCLC). METHODS DNA fragment coding for fusion protein (ldp-igf) was synthesized by linking apoprotein of lidamycin (ldp) with igf-1, and then was cloned into the plasmid pET30a. Fusion protein LDP-IGF was expressed in E.coli as inclusion bodies and was purified by Ni²⁺ affinity chromatography. Binding affinity of LDP-IGF to NSCLC cells was evaluated by immunofluorescence assay and flow cytometry-based binding assay. MTT assay was used to measure the in vitro cytotoxicity of LDP-IGF and its enediyne-energized analogue LDP-IGF-AE. PI staining assay and Annexin V-FITC/PI staining assay were used to analyze the cell cycle arrest and cell apoptosis after treatment with LDP-IGF-AE, respectively. RESULTS Active soluble LDP-IGF protein was prepared by isolation, purification, denaturation and refolding, and the production of LDP-IGF was 12 mg per liter fermentation broth. Both of immunofluorescence assay and flow cytometry-based binding assay showed that LDP-IGF has strong binding activity to NSCLC cells. Enediyne-energized fusion protein LDP-IGF-AE exhibited potent cytotoxicity to NSCLC cells in vitro, and it is more potent than that of LDM. Furthermore, fusion protein LDP-IGF without active enediyne was also cytotoxic to A549 cells at high concentrations (50 and 100 ??g??mL^-1). LDP-IGF-AE could cause significant G₂-M arrest in A549 and H460 cells, and it also induced the apoptosis in NSCLC cells in a concentration-dependent manner. CONCLUSION Fusion protein LDP-IGF-AE shows potent antitumor efficacy in vitro on NSCLC, suggesting it could be a promising candidate for targeted therapy.     

XAD-16�����֬�Զ���ù�ص���������ѧ�Ͷ���ѧ�����о�

??OBJECTIVE To investigate the adsorption thermodynamics and kinetics of enramycin on XAD-16 macroporous resin. METHODS Series of static adsorption experiments were carried out. The adsorption equilibrium data were fitted to Langmuir and Freundlich isotherm equations, which could describe the adsorption behavior of enramycin on XAD-16 macroporous resin. The thermodynamic properties were described by thermodynamic parameters. Then, pseudo-first-order model and pseudo-second-order model were applied to describe the kinetics of adsorption process. RESULTS The adsorption equilibrium data were agreed with Langmuir isotherm well. Thermodynamic analysis suggested ??H<0, and ??G<0, which indicated the adsortion procedure was a spontaneously exothermic reaction with entropy decrease. The adsorption of enramycin on XAD-16 macroporous resin could be described well by Pseudo-second-order model. CONCLUSION The adsorption thermodynamics and kinetics of enramycin on XAD-16 macroporous resin can supply the theory for the separation and purification of enramycin on XAD-16 macroporous resin.     

���������ù�ص�Ⱥ��ҩ��ѧ�о�

??OBJECTIVE To investigate the population pharmacokinetics of vancomycin (VAN) in Chinese neonates by nonlinear mixes-effects modeling software (NONMEM). METHODS One hundred and fifty-four VAN serum trough data from 91 neonatal patients were retrospectively collected from Suzhou Hospital Affiliated to Nanjing Medical University. A one-compartment model with first order elimination was used to describe structure pharmacokinetic model, and physiological maturity model was employed to screen covariates. The stability and prediction of the final model were evaluated by Bootstrap and normalized prediction distribution error (NPDE). The final model was applied to evaluate the percentage of AUC_{0-24 h}/MIC ?? 400 in neonatal patients by Monte Carlo Simulation, who were stratified according to gestational weeks, age and serum creatinine. RESULTS The weight, postmenstrual age and serum creatinine were identified as the most significant covariate on clearance. Bootstrap and NPDE showed the satisfactory stability and prediction performance of the final model. Moreover, the final model indicated that 96% of neonates with low serum creatinine (15 ??mol??L^-1) were not getting AUC_{0-24 h}/MIC??400, according to the current guidelines. CONCLUSION The population pharmacokinetic model of vancomycin in neonates is established successfully and could provide basis for the individualized therapy in neonatal patients.     

ǧ���˵Ļ�ѧ�ɷ��о�

??OBJECTIVE To investigate the chemical constituents from the stems of Lythrum salicaria L..METHODS The constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography, and TLC. The structures were identified on the basis of spectral data and physiochemical characteristics. RESULTS Twenty compounds were isolated from 70% ethanol extracts and identified as betulinic acid(1), 2??,3??,24-trihydroxy-12(13)-en-urs-28-oic acid(2), 6-O-(E)- sinapoylpoligalitol(3), feruloyl-6??-O-??-D-glucopyranoside(4), 7-oxo-??-sitosterol(5), en-tisolariciresinol(6), muramine(7), aesculetin(8), apigenin(9),(2E,6S)-2,6-dimethyl-6-O-??-D-xylpyranosyloxy-2,7-menthiafolic acid(10), quercetin3-O-(6??-caffeoyl)-??-D-galactopyranoside(11), cycloart-23-ene-3??,25-diol(12), (1??S,6??R)-8??-hydroxyabscisic acid-??-D-glucoside(13), 3??,5-dihydroxy-3,6,4??-trimethoxyl-7-O-??-D-glucopyranoside flavonoid(14), aurantiamide acetate(15), 5,6,3??,4??-tetrahydroxy-3,7-dimethoxy-flavone(16), ursolic acid(17), oleanolic acid(18), 4-O-11-methyl-oleoside-p-hydroxyphenyl-(6??-11-methyloleoside)-??-D-glucopyranoside(19), and 6-O-galloylarbutin(20). CONCLUSION Except for compounds 8 and 9, all the compounds were isolated from this plant material for the first time.
     

��������ѧ�ɷֵ��о�

??OBJECTIVE To study the chemical constituents of Catharanthus roseus. METHODS Various column chromatograghic METHODS on silica gel, Rp-18, and Sephadex LH-20 were applied for the isolation and purification of the 95% ethanol extract. The structures were elucidated by their physicochemical properties and spectral data. RESULTS Twenty-two compounds were obtained and identified as ursolic acid (1), daucesterol (2), tetrahydroalstonine (3), 7??-hydroxy-??-sitosterol (4), vindoline (5), ??-sitosterol (6), aurantiamide acetate (7), lochnericine (8), oleanolic acid (9), ajmalicine (10), (22E,24R)-ergosta-7,22-dien-3??,5??,6??-triol (11), betulinic acid (12), stigmasterol (13), quercetin (14), keampferol (15), vindorosine (16), catharanthine (17), diaaurantiamide acetate (18), reserpine (19), panarine (20), serpentine (21), and 16R-E-isositsirikine (22). CONCLUSION Compounds 4, 7, 11, 13, 18, and 20 are isolated from C. roseus for the first time.     

�轺�԰�ά��ù���������Ե��о�

??OBJECTIVE To investigate the kinetic and thermodynamic characteristics of adsorption of avilamycin on silica gel. METHODS By measuring the adsorption of avilamycin on silica gel at different temperatures, the adsorption kinetics curves and adsorption isotherm were drawn, and the kinetics and thermodynamic parameters were studied. RESULTS The adsorption of avilamycin on silica gel could be described well by Pseudo-second-order model. The adsorption process had feature of shrinking nonreactive core model, and the internal diffusion was the main rate-limiting step. The equilibrium adsorption data of avilamycin on silica gel fit the Langmuir isotherms well. The thermodynamic parameters were as follows:change in entropy (??S) was 108.115 2 J??mol^-1??K^-1, change in enthalpy (??H) was 24.654 6 J??mol^-1, and changes in free energy (??G) were -8.752 9, -8.104 3, and -7.455 6 J??mol^-1 at 309, 303 and 297 K, respectively. CONCLUSION The results of this study provide a theoretical basis for further study on the isolation and purification of high purity avilamycin by silica gel.     

�ƻ���������ɣҶ����λ��1-����Ұ��ù�صĻ����о�

??OBJECTIVE To investigate the sustained-release ability of Na-montmorillonite (Na-MMT) on 1-deoxynojirimycin (DNJ) in mulberry leaf extract (MLE). METHODS In order to prepare DNJ-MMT composite, DNJ was intercalated into the interlayer of MMT by stirring. Time and temperature for adsorption and ratio of DNJ to MMT were determined by calculating the loading of DNJ, then in vitro release experiment was carried out to estimate the sustained-release characteristics of DNJ-MMT. RESULTS DNJ-MMT composite with a drug loading of 111.64 mg??g^-1 was obtained by stirring 5.00 g Na-MMT and 16.00 g MLE containing 4 016.0 mg DNJ in 1 000 mL deionized water at 100 ?? for 1 h. The composite released DNJ quickly in water, potassium phosphate buffer (pH 7.4), and 0.1 mol??L^-1 hydrochloric acid solution. With the increasing of volume of hydrochloric acid solution, the release ratio of DNJ also increased correspondingly. CONCLUSION The sustained-release effect of Na-MMT on DNJ is proved. Na-MMT can be used for study of DNJ sustained-release preparations.     

Σ��֢�������ù��ѪҩŨ�ȼ�⼰�������ܵ�Ӱ���о�

??OBJECTIVE To study the relativity between patients?? blood concentration of vancomycin and renal function, provide references for rational clinical application.METHODS The blood concentration and renal function of 64 cases of critical patients were monitored after the usage of vancomycin,then retrospectively analyzed combined with clinical date(basic information,bacteriological RESULTS ,clinical curative effect,etc.). RESULTS Pathogenic bacteria was detected from 40 of 64 patients, accounting for 62.5%. The effective rate of vancomycin reached 81.25%. The average value of 79 monitered cases of valley concentration was (17.48??13.22)??g??mL^-1. There was no significant difference of the level of BUN and Scr before and after the treatment of vancomycin,while the level of Ccr had the significant difference. There were significant difference of the level of BUN, Scr, Ccr between the groups of valley concentration <5, 5-10, 10-20 ??g??mL^-1 and the group of >20 ??g??mL^-1. CONCLUSION The application of vancomycin in critical patients is relatively cautions.When using the drug,the drug concentration and renal function can be adjusted according to the RESULTS of blood concentration and renal function.     

������E������ù�ضԲ�̼��ùϩø���׿��ײ��������⿹�������о�

??OBJECTIVE To evaluate the antibacterial effects of colistin combined with fosfomycin against Klebsiella pneumoniae carbapenemase-producing K. pneumonia in vitro. METHODS The minimal inhibitory concentration(MIC) of colistin and fosfomycin against 74 strains of KPC-Kp was determined by agar dilution method and broth microdilution method respectively.The fractional inhibitory concentration index( FICI )was calculated by checkerboard method to determine the combined effect.SixKPC-Kp strains were randomly selected to determine the time-killing curves of colistin and fosfomycin alone or in combination. RESULTS The MIC results: polymyxin sensitivity rate of 100%, fosfomycin sensitivity rate of 35.14%.The FIC results: In 74 strains,12.16% synergism, 39.19% section synergism,6.76% additive effect,41.89% irrelevant,no antagonism found.The results of time-kill assay showed that there was a significant synergistic effect between colistin and fosfomycin in fosfomycin-sensitive strains, while fosfomycin-resistant strains showed no synergistic effect. CONCLUSION In the case of fosfomycin-sensitive strains, the combination of colistin and fosfomycin has synergistic effects on KPC-Kp in vitro, and time-kill assay also shows a good synergistic effect. Resistant strains are poor in synergism.     

�����������ð����϶�̼��ùϩ����ҩͭ�̼ٵ������Ŀ������ü������о�

??OBJECTIVE To explore the antibacterial activity and mechanism of fusidic acid combined with aztreonam on 12 clinical isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA). METHODS Broth dilution method was used to determine the minimum inhibitory concentration(MIC) of the fusidic acid and aztreonam combination.The MIC of two drugs combination were measured by the checkerboard method and partial inhibitory concentration index (FIC) was calculated to determine the combined effect.The synergistic effect of two drugs was assessed by the disk diffusion susceptibility test and the time-killing curves.Extracellular enzyme activity assay was used to detect the strains extracellular enzyme activity changes of fusidic acid alone and combined with aztreonam. The probable mechanism of the combined use of two drugs was discussed. RESULTS Fusidic acid and aztreonam combination displayed synergistic and additive activity on 61.54% and 38.46% isolates, no antagonism activity was observed.The bacteriostasis circle was obviously increased in two drugs combination, of which 41.67% of the strains were changed from drug resistance to sensitive. The time-killing curves showed that the combined of two drugs had bactericidal effect on the isolate PA 320.Extracellular aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity were all increased in a significant difference with the combination of two drugs. CONCLUSION Fusidic acid combined with aztreonam on CRPA is showed synergistic and additive activity in vitro. The mechanism of two drugs in combination may concern with aztreonam help the fusidic acid to overcome the natural hydrophobic antibiotic permeability barriers of gram-negative bacteria.     

注射用七叶皂苷与地塞米松注射液配伍稳定性研究

 目的 在4、25、37 ℃下研究地塞米松磷酸钠注射液和七叶皂苷钠粉针的配伍稳定性。方法 将地塞米松磷酸钠注射液、七叶皂苷钠粉针按照临床用药浓度分别溶解于5%葡萄糖注射液和0.9%氯化钠注射液中,比较配制溶液后0、1、2、4、8、12 h时地塞米松磷酸钠、七叶皂苷A和七叶皂苷B的含量变化、pH值、不溶性微粒数、外观。结果 在4、25 ℃条件下,12 h内,两种药物配伍稳定性良好,在37 ℃时两种药物配伍稳定性较差。结论 地塞米松磷酸钠注射液和七叶皂苷钠粉针溶液可以配伍使用,配伍后应于阴凉处储存,并于12 h内输注完毕。     

���᰺��˾��ע��Һ��ע���õ������������Ƶ������������о�

??OBJECTIVE To investigate the compatibility of dexamethasone sodium phosphate injection and ondansetron hydrochloride injection. METHODS The dexamethasone sodium phosphate injection and ondansetron hydrochloride injection were dissolved with 5% glucose injection and 0.9% sodium chloride injection respectively at commonly used concentrations in clinic. The contents of dexamethasone sodium phosphate and ondansetron hydrochloride were determined by HPLC at 0,3,6,and 24 h after the preparation of solution. Meanwhile,the pH and number of indiscerptible particles in these solutions were also determined. RESULTS The mixtures of the two drugs were highly stable within 24 h,without obvious change in pH and color. The numbers of insoluble particles greater than 10 and 25 ??m were acceptable. CONCLUSION Dexamethasone sodium phosphate injection is compatible with ondansetron hydrochloride injection.     

替加氟注射液配伍0．9％氯化钠注射液的稳定性研究

目的考察替加氟注射液在0．9％氯化钠溶液中配伍的稳定性。方法观察室温、避光、冷藏,24h内替加氟注射液0．9％氯化钠溶液的外观、pH值变化,观察配伍液中不溶性微粒的变化,并采用高效液相色谱法考察配伍液中替加氟的变化。结果配伍液在24h内无浑浊、沉淀、气体产生,颜色、pH值、不溶性微粒数无明显变化;24h内替加氟注射液在0．9％氯化钠注射液中无明显变化。结论在实验条件下,24h内替加氟注射液在0．9％氯化钠注射液中稳定。     

高效液相色谱法测定甲氰咪胍氯化钠注射液的含量

目的建立高效液相色谱(HPLC)法测定甲氰咪胍氯化钠注射液的含量。方法分析柱为ODSC18(4.6 mm×200mm,5μm);流动相为甲醇-磷酸盐缓冲液(30∶70);检测波长218 nm。结果甲氰咪胍氯化钠注射液的线性范围为6.4~19.2μg/m l(r=1.000 0),平均回收率为99.76%,RSD为0.49%(n=9)。结论该方法简便、准确、重现性好,能够满足西咪替丁的药品质量监控。     

双黄连粉针剂与头孢唑啉钠配伍的稳定性考察

目的　考察双黄连粉针与头孢唑啉钠注射液在生理盐水中配伍的稳定性。方法　采用高效液相色谱法对两药混合后的稳定性进行考察。结果　在 37℃条件下观察 6 h,配伍液的外观、p H值及两药含量均无明显变化。结论　实验证明两药可在生理盐水中配伍使用。     

高效液相色谱法测定盐酸阿扎司琼氯化钠注射液中阿扎司琼的含量

目的：研究盐酸阿扎司琼氯化钠注射液中盐酸阿扎司琼的定量分析方法。方法：采用高效液相色谱法．色谱柱：Shim—Pack CLC—ODSC18（250mm×4．5mm,5μm）分析柱;流动相：磷酸二氢钾-乙腈（95：5V／V）,流速：0．5mol·ml^-1;测定波长216nm;柱温40％。结果：盐酸阿扎司琼在2．5～15μg·ml^-1（r=0．9997,n=6）呈现良好的线性关系,平均回收率为99．23％,RSD为0．73％。结论：本方法操作简便、精密度好,适用于盐酸阿扎司琼氯化钠注射液的质量控制。     

注射用辛芍冻干粉针药味配伍作用研究

目的：研究注射用辛芍冻干粉针组方中灯盏细辛与赤芍的配伍关系,以阐明该复方药对配伍的合理性。方法：采用小鼠急性全脑缺血、缺氧模型,以动物呼吸维持时间和张口喘息时间为指标。以Scott比值法求得各单组分和配伍条件下的“半效作用量”（D50）,应用Finney调和平均数法及Loewe等效线法评价药物的配伍作用。结果：赤芍与灯盏细辛以四种不同比例的配伍用药,对急性脑缺血小鼠呼吸维持时间及急性脑缺氧小鼠喘息时间指标的调和平均数值Q50均小于1,合并用药的等效曲线均为凹形。综合指标表明灯盏细辛与赤芍最佳组方配比1∶1.5。结论：复方药对灯盏细辛与赤芍配伍用药存在协同作用,注射用辛芍冻干粉针组方配伍合理。     

红花黄色素氯化钠注射液联合复方樟柳碱注射液对NPDR患者的临床疗效

目的观察红花黄色素氯化钠注射液联合复方樟柳碱注射液对非增殖型糖尿病视网膜病变(NPDR)患者的临床疗效。方法 68例(102只眼)患者随机分为对照组(32例,48只眼)和观察组(36例,54只眼),对照组予以常规治疗,观察组在常规治疗基础上予以红花黄色素氯化钠注射液联合复方樟柳碱注射液,比较2组治疗前后视力、眼底出血、渗出、微血管瘤和黄斑中心厚度的变化。结果治疗后观察组视力恢复、眼底改善、黄斑中心厚度控制显著优于对照组(P0.05,P0.01)。结论红花黄色素氯化钠注射液联合复方樟柳碱注射液可有效改善NPDR患者的视力,延缓疾病进展。     

非PVC软袋包装碳酸氢钠注射液的可行性探讨

目的研究非PVC软袋包装碳酸氢钠注射液的可行性。方法配制碳酸氢钠注射液包装于非PVC软袋中,考察膜的透过性对碳酸氢钠注射液pH值的影响。结果用隔离膜保护非PVC软袋装碳酸氢钠注射液,可以保持溶液pH值稳定。结论非PVC软袋可用于碳酸氢钠注射液的包装。     

丹参川芎嗪注射液联合肌苷氯化钠注射液治疗冠心病临床研究

目的：观察丹参川芎嗪注射液联合肌苷氯化钠注射液治疗冠心病的临床疗效。方法：选取92 例冠心病患者,按照随机数字表法分为对照组和观察组,每组46 例。2 组均给予β 受体阻滞剂、硝酸甘油、钙离子通道阻滞剂等常规药物治疗,对照组在此基础上使用肌苷氯化钠注射液治疗,观察组在对照组基础上加用丹参川芎嗪注射液治疗,2 组均治疗14 d。比较2 组治疗前后左心室射血分数、内皮细胞功能及血脂指标;比较2 组临床疗效及不良反应发生率。结果：治疗后,2 组左心室射血分数、一氧化氮、前列环素、高密度脂蛋白（HDL） 水平均较治疗前升高（P＜0.05）,甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白（LDL） 水平均较治疗前降低（P＜0.05）;观察组左心室射血分数、一氧化氮、前列环素、HDL 水平均高于对照组（P＜0.05）,TG、TC、LDL 水平均低于对照组（P＜0.05）。观察组临床疗效优于对照组（Z=1.660,P＜0.05）。观察组不良反应发生率为13.04%,对照组不良反应发生率为8.70%,2 组比较,差异无统计学意义（P＞0.05）。结论：丹参川芎嗪注射液联合肌苷氯化钠注射液治疗冠心病可以有效改善患者的心功能、内皮细胞功能及血脂水平,且用药不良反应未见明显增加。