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??OBJECTIVE To explore the effects of Dracocephalum total flavonoids(TFDM) on myocardial ischemia/reperfusion injury(MIRI)induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 min and reperfusion 120 min, by ligation of left anterior descending coronary artery. TFDM(30 mg??kg^-1??d^-1) and autophagy activator(1 mg??kg^-1??d^-1) or inhibitor(25 mg??kg^-1??d^-1) pretreatment was given before making the model. The MIRI-induced infarct size, the activities of lactate dehydrogenase(LDH), creatine kinase isoenzyme(CK-MB) in plasma and apoptosis protein caspase-3 in tissue and the expression level of autophagy-related proteins LC3, Beclin-1 were observed. RESULTS Compared with model group, the experiment revealed that autophagy inhibitor alleviated MIRI-induced myocardial damage by decreasing the infarct size, myocardial enzyme LDH and CK-MB leak; and reducing apoptosis protein caspase-3 activity level. In addition, TFDM pretreatment significantly inhibited the expression of autophagy-related proteins LC3 and Beclin-1. CONCLUSION TFDM shows inhibitory effects on MIRI-induced autophagy,which may play an important role in the protection against MIRI.     

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??OBJECTIVE To explore how to carry out pharmaceutical consultation for anti-infection treatment in neutropenic hematological patients with invasive fugal disease and elaborate the value of clinical pharmacists in anti-infection treatment. METHODS A total of 41 hematologic malignancies patients with invasive fungal disease who were consulted by clinical pharmacist from October 2014 to June 2016 were enrolled into the study. The etiology, bacteria complication,and infection site were summarized. The other 41 agranulocytosis patients complicated with invasive fungal disease without clinical pharmacist consultation randomly sampled by HIS were used as the control. Statistical analysis were carried out to evaluate the effect of anti-infection treatment. The authors also discussed that as a clinical pharmacist how to carry out pharmaceutical consultation through several typical anti-fungal infection cases. RESULTS Totally 45 strains of fungi were isolated from the secretion specimens obtained from the 41 patients, including Candida albicans, Candida glabrata, Candidakrusei, Candida tropicalis, Aspergillums, and Cryptococcosis, among which Candida albicans accounted for 60.0%, followed by Aspetgillus (13.3%), Candidakrusei (11.1%), Candida glabrata (6.67%), Candida tropicalisi (6.67%), and Cryptococcosis (2.2%). The main infection site was the lung, followed by the digestive tract and blood stream. The positive rate of bacteria culture was 58.5% among the 41 patients, and the major isolated bacteria were Escherichia colis, Pseudomonas aeruginosa, Enterococcus, and Pseudomonas maltophilia. For the antifungal treatment involving the clinical pharmacists, the cure rate was 48.8%, the significant effective rate was 34.2%, the improved effective rate was 7.4%, the total effective rate of treatment was 72.9%, and the failure rate was 9.3%. There was significant difference in the curative effect between the clinical pharmacist consultation group and the control group (P<0.05). CONCLUSION The incidence of fungal infection in agranulocytosis patients is high, and most of the patients are complicated with bacteria infection. The most frequently infected site is respiratory tract. Clinical pharmacists can play an important role in the treatment of invasive fungal disease in agranulocytosis patients to ensure the treatment safety and efficacy.     

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??OBJECTIVE To establish a high-performance capillary electrophoresis (CE) method for determinating gallic acid in commercial Quanshen pieces of two different colors,amaranth and brownish red. METHODS CE-UV method was used in the following condition: BGE 20 mmol??L^-1 sodium borate solution, voltage 20 kV, detection wavelength 290 nm, sample injection 10 s at 5 kPa, capillary temperature room temperature. RESULTS A quantitative method was successfully developed to determine gallic acid in Quanshen pieces within 6 min. The contents of gallic acid in 7 batches of amaranth colored Quanshen pieces were 2.70% (Hubei province), 12.08% and 7.79% (Shandong province), 2.01%, 5.78%, 6.97%, and 4.22% (Hebei province), respectively. The contents of gallic acid in brownish red colored Quanshen pieces were 1.35% (Hubei province), 1.81% and 3.42% (Shandong province), 1.87%, 3.42%, 0.44%, and 1.52% (Hebei province), respectively. CONCLUSION The method is rapid, economical and simple and can provide a powerful quality control measure for Quanshen pieces. The contents of gallic acid in the amaranth colored Quanshen pieces are higher than those in the brownish red colored pieces.     

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??OBJECTIVE To evaluate the inhibitory effects and mechanism of Hydrochloric acid chlorobenzene sulperzon (HACS) on neuronal inflammation were studied in order to evaluate possible application of it in AD therapy. METHODS The release of NO (nitric oxide) by astrocyte was detected by Griess methods and the chemotaxis of mouse macrophage was detected by Boyden chemotaxis chamber. The cell viability was detected by MTT assay. The content of IL-6 and RANTES (T cell expressed and presumably secreted)was determined by ELISA. The expression of mRNA of IL6 and RANTES was detected by RT-PCR. The intracelluar Ca²⁺ was detected by confocal microscope. RESULTS HACS efficiently decreased the release of NO from astrocyte stimulated by LPS (1 ??g??mL^-1), chemotaxis of mouse macrophage stimulated by PAF (5??10^-8 mol??L^-1), expression of IL-6 and regulated upon activation of RANTES in U251 cells induced by IL-1?? (50 ng??mL^-1). In addition, HACS significantly inhibited the increase of intracellular Ca²⁺ in U251 cells induced by A??1-42(50 ??g??mL^-1)/ sodium glutamate(100 ??mol??L^-1)or IL-1??(50 ng??mL^-1). CONCLUSION HACS efficiently inhibites the activation of astrocyte by regulation of intracelluar Ca²⁺inhibition of chemotaxis and decrease of inflammatory cytokines. Especially, the inhibition of RANTES and intracelluar Ca²⁺ induced by inflammatory mediators by HACS is firstly reported in this study.     

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??OBJECTIVE To identify the specific cytochrome P450 (CYP) enzymes involved in the metabolism of dipfluzine hydrochloride (Dip) in the rat liver microsomes. METHODS The rat liver microsomes were prepared and incubated with Dip. The Dip metabolites (M1, M2, M4 and M5) were identified by LC-MS/MS, and the CYP isoenzymes were identified by the combination of the selective CYP inhibitor study, correlation analysis and a panel of recombinant rat CYP expereiment, respectively. RESULTS The RESULTS from the experiments of selective CYP inhibitors, correlation analysis and recombinant rat CYP isoenzymes indicated that CYP2A1, CYP3A and CYP2C11 contributed to the formation of M1 and M5 in the rat liver microsomes. CYP3A, CYP2A1, CYP1A2, CYP2C11 and CYP2E1 metabolized Dip to M2. CYP3A, CYP2A1, CYP2E1 and CYP2C11 contributed to M4 formation. And the recombinant rat CYP researches further indicated that CYP3A2 exhibited more activity than CYP3A1. CONCLUSION CYP3A and CYP2A1 are the major CYP isoenzymes responsible for catalyzing Dip to the four metabolites formation in the rat liver microsomes.     

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??OBJECTIVE To investigate the possible mechanism of Panax notoginseng saponins (PNS) protection against cisplatin-induced kidney injury through enhangcing autophagy. METHODS The rats were randomly divided into normal control group, cisplatin model group and cisplatin+PNS group. After exposure to cisplatin for 4 and 8 d, the urinary ??-N-acetyl-??-D-glucosaminidase (NAG), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured by commercial kits, and the pathological change of renal tissue was examined using transmission electron microscopy. Additionally, the expression of LC3, HIF-1??, BNIP3 and Beclin1 were examined by Western blotting. RESULTS PNS decreased the levels of urinary NAG, serum BUN and Scr which were increased by cisplatin (P??0.05). Moreover, PNS significantly increased the expression of LC3, HIF-1??, BNIP3 and Beclin1 (P??0.05), and attenuated the mitochondrial damages of renal cells. Furthermore, the effects of PNS on the mentioned above were more obvious at day 8 than that at day 4 (P??0.05). CONCLUSION PNS may play a protective role against cisplatin-induced kidney injury with certain of time dependence, by enhancing mitochondrial autophagy in rat renal tissue via the HIF-1??/BNIP3 pathway.     

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??Anthracyclines generally possess antitumor activities and they are clinically broad-spectrum anticancer antibiotics. But some of them have prominent toxicities and drug resistances. These limit their further development and applications. However, proper structural modifications can sometimes solve these problems. So lots of new anthacyclines are obtained through total-synthesis or partial-synthesis for the purpose of finding more effective new drugs. In this paper, combing with our previous work and referring the literatures, we briefly introduce the mechanism, drug resistance, cardiac toxicity of anthracycline, and mainly review the structure-activity relationships of ring A, sugar moieties and twin drugs of anthracyclines. These can provide powerful evidence for further developments of new anthracyclines.     

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??OBJECTIVE To analyze of the characteristics of single nucleotide polymorphisms of the commonantineoplastics in the treatment of gastric cancer and colorectal cancer in our hospital. METHODS Venous blood was collected from patients with digestive tract tumor, and the drug related gene loci were detected by fluorescence staining in situ hybridization. The original data are stored in Microsoft Excel to establish a database for routine statistics and chi square test was conducted to determine whether the distribution of allele frequency distribution is in accordance with the law of Hardy Weinberg. RESULTS A Total of 1 743 loci of 14 drug related genes were detected in 242 patients. The loci genotype distribution were in accordance with Hardy Weinberg equilibrium except dihydrotestosterone dihydropyrimidine dehydrogenase gene (DPYD), methylenetetrahydrofolate reductase gene (MTHFR) and cytochrome P4501B1 gene (CYP1B1). CONCLUSION The patients with digestive tract tumor in China have their own characteristics in single nucleotide polymorphisms of drug related genes. We should take this as the basis for accurate anti-tumor drug treatment.     

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??OBJECTIVE To analyze the individual features of mycophenolate mofetil exposure in renal transplantation patients receiving immunosuppressive therapy postoperatively to provide reference for clinical individualized medication.METHODS Ninety-seven cases of renal transplantation patients were included in the study, with mycophenolic acid blood concentrations determined by HPLC method. The mycophenolic acid exposure characteristics was analyzed,using the domestic and foreign recommended drug exposure target value of 30-60 μg·h·mL^-1 as reference. SPSS20.0 was used to analyze the data.Normal distribution diagram was drawn for the data and single factor analysis of variance with a completely randomized design was performed to compare the drug exposures under different conditions.RESULTS The study included 526 cases of mycophenolic acid plasma concentration data. The trough concentration was (2.51±1.79) μg·mL^-1, and 332 cases reached the recommended plasma concentration range. The average plasma concentration was (2.08±0.71) μg·mL^-1, and the target achievement rate was 63.0%. There was no significant difference in the plasma concentrations between male and female patients (P>0.05). The plasma concentrations were significantly different between middle-aged (18-64 y) and elderly (65 to 77 y) patients (P<0.05). There was no significant difference in the plasma concentrations among different dosage groups (P>0.05). Between the different treatment groups, ie MMF+CsA+Pre group and MMF+FK506+Pre group (P=0.00), MMF+CsA group and MMF+FK506 group (P=0.00), MMF+FK506+Pre group and MMF+CsA group (P=0.00), MMF+CsA+Pre group and MMF+FK506 group (P=0.00), the plasma concentrations were significantly different (P<0.05). There was no statistically significant difference in the plasma drug concentrations among patients with different GFRs (P>0.05).CONCLUSION There is remarkable inter-individual difference in the plasma concentration of mycophenolic acid, and a variety of clinical factors affect the drug exposure. Therefore, it is necessary to carry out therapeutic drug monitoring for mycophenolic acid in order to lay the foundation for individualized treatment.     

绿原酸衍生物的合成及体外抗肿瘤活性研究

目的设计并合成天然产物绿原酸的酰胺类衍生物,并对该系列化合物进行体外抗肿瘤活性研究。方法以绿原酸为起始原料,经保护、缩合、脱保护3步反应制得目标产物。采用噻唑蓝(MTT)法,考察所合成的目标化合物对人宫颈癌HeLa细胞、人肝癌HepG2细胞和人盲肠腺癌HCT-8细胞3种肿瘤细胞的体外增殖活性的影响。结果设计并合成了10个绿原酸取代的苯甲酰胺及苯乙酰胺类衍生物B1~B5、C1~C5,其结构均经1H-NMR、13C-NMR及HR-ESI-MS确定。抗肿瘤活性测试结果表明,10个绿原酸衍生物对3株肿瘤细胞株表现出不同程度的抑制效果,其中衍生物B2对HeLa细胞表现出良好的活性,且活性优于阳性对照药顺铂,所有的衍生物均对HCT-8细胞表现出抑制作用,且均优于阳性对照药顺铂。结论10个绿原酸衍生物均为新化合物,部分衍生物具有较好的抗肿瘤活性,值得进一步深入研究。     

槐果碱肉桂酸酯衍生物的合成与抗肿瘤活性研究

目的合成槐果碱肉桂酸酯衍生物,并对衍生物进行体外抗肿瘤活性评价。方法以槐果碱为起始原料,通过氧化、酯化、N-烷基化、还原、缩合、水解、成盐等反应得到目标化合物。采用噻唑蓝(MTT)法考察所合成的目标化合物对HeLa、Hep G2和A-549 3种肿瘤细胞的体外抗增殖活性。结果合成了11个槐果碱肉桂酸酯衍生物,其结构经1H-NMR、13C-NMR及HRMS确定,活性测试结果表明,部分衍生物表现出良好的抗肿瘤活性,其中,化合物5g对3种肿瘤细胞均表现出良好的抗肿瘤活性,且活性优于阳性对照药顺铂。结论部分衍生物表现出良好的抗肿瘤活性,化合物5g具有进一步研究价值。     

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??OBJECTIVE To study the synthesis and antitumor activity of novel quinolone derivatives. METHODS Based on the structure of ciprofloxacin, the objective substances were designed and synthesized according to the principle of fragment-based drug discovery. Their anti-tumor activities in vitro were evaluated against A549, HL-60, and Hela cells by MTT assay. Molecular docking studies were performed with the Libdock protocol of Discovery Studio to afford the ideal interaction mode of the compound with the binding site of the Topo ??. RESULTS Eight novel compounds were synthesized and showed potential antitumor activities. CONCLUSION The antitumor activities of the synthesized quinolone derivatives are worthy of further study.     

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??OBJECTIVE To synthesize 5-substituted indole-3-deoxypodophyllotoxin derivatives and study their antitumor activity. METHODS The target compounds were synthesized through a series of reactions and their anti-tumor activity in vitro were evaluated against Hela, K562 and K562/A02 cell lines by MTT as assay. RESULTS Ten target compounds were synthesized and confirmed by ¹H-NMR, ¹³C-NMR, and HR-ESI-MS. All the target compounds had different degrees of cytotoxic activity in vitro. Most of the compounds had significant anti-MDR activity in vitro. CONCLUSION 5-Substituted indole-3-deoxypodophyllotoxin derivatives have good antitumor activity and worth of further study.     

西松烷型二萜衍生物的合成及抗肿瘤活性研究

目的基于西松烷型二萜天然产物新巴豆瑞士松酸进行结构修饰,并对得到的衍生物进行体外抗肿瘤活性评价。方法以新巴豆瑞士松酸为起始原料,通过缩合反应、点击化学反应得到目标化合物。采用噻唑蓝(MTT)法考察所合成的目标化合物对HeLa、K562和K562A/02肿瘤细胞的抗增殖活性。结果合成了11个文献未报道的新巴豆瑞士松酸衍生物,其结构经~1H-NMR、~(13)C-NMR及HR-MS确定。活性测试结果表明,部分衍生物表现出一定的抗肿瘤活性,其中,化合物2f对HeLa细胞表现出良好活性,化合物2e对K562和耐药的K562A/02细胞表现出良好活性。结论部分衍生物对耐药的K562A/02细胞表现出抗肿瘤活性,具有进一步研究价值。     

槲皮素-3-O-酰基酯的合成及抗肿瘤活性研究

目的 合成槲皮素-3-O-酰基酯,探索抗肿瘤活性。方法 以芦丁为原料,经苄基化保护、酸水解、酯化反应,再经钯/碳(Pd/C)催化加氢脱苄基得到12种槲皮素-3-O-酰基酯,使用红外(IR)、氢谱(¹H-NMR)、碳谱(¹³C-NMR)、液质联用(ESI-MS)测定结构,采用邻二氮菲法和1,1-二苯-2-苦基肼(DPPH)法考察了12种目标化合物的抗氧化活性,采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(MTT)法测定抗肿瘤活性。结果 光谱确定了目标化合物的结构,抗氧化性实验显示,大部分目标化合物的清除率(SC₅₀)小于槲皮素或与槲皮素相当,提示3-OH不是槲皮素抗氧化活性的必需基团,目标化合物对人食管癌细胞EC109、人食管鳞癌细胞EC9706、人胃癌细胞MGC-803、人前列腺癌细胞PC-3四株肿瘤细胞的体外增殖抑制作用增强。结论 合成了12个目标化合物,与母体槲皮素比较,对肿瘤细胞的增殖抑制作用显著增强。     

乌苏烷型-2,12-烯-28-羧酸酯的合成及其体外抗肿瘤活性研究

目的设计合成了乌苏烷型-2,12-烯-28-羧酸酯类化合物,并对其进行了体外抗肿瘤活性研究。方法熊果酸先进行C28-羧基与卤代烃发生酯化反应,然后C3-羟基与甲基磺酰氯在0℃冰浴条件下发生甲基磺酰化反应,最后在168℃回流条件下发生消除反应,从而得到目标产物;通过MTT法对上述合成的乌苏烷型-2,12-烯-28-羧酸酯类化合物进行体外抗肿瘤活性研究。结果设计并合成了7个目标产物3a~3g,利用IR、MS和1H-NMR确证了结构;抗肿瘤活性筛选结果表明3b对A549肿瘤细胞的抑制率略低于阳性对照药吉非替尼。结论此路线操作简单,设计合理,对进一步开展熊果酸的结构改造和抗肿瘤活性研究具有一定的参考价值。     

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??OBJECTIVE To investigate the chemical constituents in chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg and their antitumor activities. METHODS Various chromatography techniques such as column chromatography on silica gel, Sephadex LH-20 and preparative TLC were used to isolate and purify the compounds. Their structures were identified by¹H-NMR,¹³C-NMR and MS. Their antitumor activities was tested by MTT method. Moreover, the other compounds of chloroform extraction were detected by GC-MS. RESULTS Six compounds were isolated by classic chromatography and identified as ??-sitosterol(1), 4-hydroxy-3-methoxybenzaldehyde(2), oleanolic acid (3), 5-hydroxymethyl furfural(4), azelaic acid(5), vanillic acid(6). Twenty-two compounds were identified by GC-MS. CONCLUSION Compounds 2-6 are isolated from this plant for the first time. Compounds 1 and 3 shows strong cytotoxic activities against Hela229 with IC₅₀ values of 40.78, 25.69 ??g??mL^-1, respectively. Compound 3 also showed strong cytotoxic activities against with IC₅₀ values of 69.87 ??g??mL^-1. The result proved that antitumor activity of chloroform extraction of Tetrastigmatis hemsleyani diels et. Gilg is due to the contribution of multi-components.
     

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??OBJECTIVE To design and synthesize series of quercetin derivatives by introducing allyl or prenyl groups and investigate their antitumor activities in vitro.METHODS Compounds 2, 3, 4, 5, 6, 7 and 8 were synthesized with quercetin as starting material through the etherification reaction.The antitumor activities were evaluated by MTT assay against human lung cells (A549), human breast cancer cells (MDA-MB-231), and human hepatoma cells (HepG2).RESULTS Two allyl-substituted and five prenyl-substituted quercetin derivatives were synthesized. Compounds 4, 5, 6, 7, and 8 were new compounds, and their structures were characterized by ¹H-NMR and ¹³C-NMR. Compounds 6 and 7 exhibited observable anti-proliferative activity. Compound 6 inhibited the growth of A549, MDA-MB-231, and HepG2 cells with IC₅₀ values of 15.23, 16.56, and 12.32 ??mol??L^-1, respectively.Compound 7 restrained the growth of A549 and MDA-MB-231 cells with IC₅₀ values of 8.92 and 2.90 ??mol??L^-1, respectively. CONCLUSION Compounds 6 and 7 synthesized by introducing prenyl groups into quercetin have significant anti-tumor activities, which are worth of further research.     

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??OBJECTIVE To synthesize the derivatives of 8-amino benzofuran[3,2-d]pyrimidine and study their anticancer activities.METHODS The target compounds were synthesized through a series of reactions, and their anticancer activities in vitro were evaluated against COLO205, MCF-7 and K562 cell lines by MTT as assay. RESULTS Nine title compounds were synthesized and confirmed by EI-MS,¹H-NMR and ¹³C-NMR.Compounds 2, 3d and 5c had good inhibition effect against COLO205, MCF-7 and K562 cells.The inhibition rates of compound 5c against COLO205, MCF-7 and K562 cells were 99.58%,78.75% and 98.68% respectively at 10^-4 mol??L^-1. CONCLUSION The anticancer activity of benzofuran[3,2-d] pyrimidine derivatives is worthy of further study.