2.A multi-center clinical trial of recombinant human thrombopoietin in the treatment of chemotherapy-induced thrombocytopenia in patients with solid tumor.
Chun-mei BAI ; Guang-xun XU ; Yong-qiang ZHAO ; Shao-mei HAN ; Yuan-dong SHAN
Acta Academiae Medicinae Sinicae 2004;26(4):437-441
OBJECTIVETo assess the efficacy and safety of recombinant human thrombopoietin (rhTPO) on chemotherapy-induced thrombocytopenia in patients with solid tumor.
METHODSIn this randomized crossover self-controlled multi-center clinical trial, 154 patients with solid tumor were randomly divided into two groups (group A 77 cases and group B 77 cases). All patients were given the same two cycles of chemotherapy. In group A, the first cycle was treated cycle, in which patients were given rhTPO, while the second cycle was non-treated cycle as a control. In group B, the first cycle was non-treated cycle as a control, while the second cycle was treated cycle. RhTPO 1.0 microg/(kg x d) was administered subcutaneously 6-24 hours after chemotherapy for the longest 14 days. Laboratory tests included complete blood counts, urinalysis, serum chemistry, coagulant test, chest radiography, and electrocardiogram. Serum samples were screened for anti-rhTPO antibodies.
RESULTSIn both group A and group B, platelet decrease and duration had no significant difference between the treated cycle and non-treated cycle. Platelet count was higher in the treated cycle, than in the non-treated cycle: [minimal mean platelet count (64.4 +/- 45.4) x 10(9) cells/L and (52.4 +/- 30.9) x 10(9) cells/L (P=0.000), maximal mean platelet count (263.9 +/- 142.5) x 10(9) cells/L and (148.9 +/- 67.7) x 10(9) cells/L (P=0.000)]. Duration of thrombocytopenia was shorter in the treated cycle than in the non-treated cycle [days with platelet count < 50 x 10(9) cells/L, (2.5 +/- 3.9) and (3.7 +/- 5.7) (P=0.04); days with platelet count recovered > or = 75 x 10(9) cells/L, (10.3 +/- 8.7) and (14.0 +/- 8.9) (P=0.000), and days with platelet count recovered > or = 100 x 10(9) cells/L, (15.9 +/- 10.5) and (21.1 +/- 9.5) (P=0.000)]. The need for platelet transfusion was not significantly reduced in treated cycle. The effects of rhTPO on WBC, Hb, hepatic function, renal function, and coagulant function were not found. Transient low-titer non-neutralizing antibody was developed in one patient. Therapy with rhTPO was tolerated by all patients. Mild side effects were observed in individual patients, including fever, dizziness, and chill. Conclusion Administration of rhTPO after chemotherapy can significantly reduce the degree and duration of thrombocytopenia and promote platelet recovery. Therapy with rhTPO seems to be safe.
Adolescent ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cross-Over Studies ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Neoplasms ; blood ; drug therapy ; Platelet Count ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombocytopenia ; chemically induced ; drug therapy ; prevention & control ; Thrombopoietin ; therapeutic use
3.Effects of ischemic postconditioning on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.
Lu SHI ; Xu-Guang JIA ; Min LUO ; Ya-Kun LIU ; Shan ZHAO ; Hai-E CHEN ; Ying-Chun MA ; Dan CHEN ; Wan-Tie WANG
Chinese Journal of Applied Physiology 2014;30(1):60-63
OBJECTIVETo investigate the effects of ischemic postconditioning (IPostC) on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.
METHODSAdult male SD rats were randomly divided into 3 groups based upon the intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR), LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue was accessed by quantitative immunohistochemistry (MHC) and Bcl-2, Bax mRNA by RT-PCR.
RESULTSIPostC could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax showed that IPO significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/Bax ratio (P < 0.01) .
CONCLUSIONIPostC may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by inhibiting oxidant generation and neutrophils filtration.
Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Ischemic Postconditioning ; Lung ; metabolism ; pathology ; Lung Injury ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Peroxidase ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism
4.Effects of silencing connective tissue growth factor on rat transforming growth factor beta/Smads signal.
Guang-ming LI ; Ding-guo LI ; Qing XIE ; Chun-hua ZONG ; Shan JIANG ; Han-ming LU
Chinese Journal of Hepatology 2008;16(11):840-843
OBJECTIVETo investigate the effects of small interfering RNA targeting connective tissue growth factor (CTGF) on rat transforming growth factor beta (TGF beta)/Smads signal pathway.
METHODSChemically synthetic siRNA targeting CTGF was transfected into HSC T6 and then they were injected into rat livers through their intraportal veins. At the same time these rats also received CCl4 subcutaneously every three days for 6 consecutive weeks. Untreated HSC T6 or/and rats with random siRNA treatment served as controls. Total RNA or/and protein in HSC T6 and rat hepatic tissues were extracted. The expressions of CTGF and TGF beta 1, Smad2, 3 and 7 genes were detected by reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot.
RESULTSCTGF siRNA significantly reduced the expression of CTGF protein in HSC T6. At 48 h after CTGF siRNA treatment, the down-regulation of CTGF protein was the most significant, up to 94%+/-4% (t=46.196, P less than 0.01), but the expressions of TGF beta 1, Smad2, 3 and 7 mRNA showed no differences in HSC T6 compared with the blank controls. Six weeks after CCl4 injections, prominent up-regulations were observed in the gene expressions of CTGF and TGF beta 1 in saline control or siRNA-treated rat livers. Administering CTGF siRNA for six weeks markedly attenuated the induction of CTGF and TGF beta 1 genes; the expressions of CTGF and TGF beta 1 protein decreased by 95%+/-2% (F=21.234, P less than 0.01) and 74%+/-8% (F=13.464, P less than 0.05), respectively, whereas Smad2, 7 protein expressions were not affected.
CONCLUSIONSilencing the CTGF gene can suppress the TGF beta /Smads signal pathway in rat livers.
Animals ; Connective Tissue Growth Factor ; metabolism ; Gene Silencing ; Male ; RNA, Messenger ; genetics ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad Proteins ; metabolism ; Transfection ; Transforming Growth Factor beta ; metabolism
5.Expression of hypoxia inducible factor-1α and correlated target genes in human laryngeal carcinoma.
Ou XU ; Xiao-ming LI ; Mao-xin WANG ; Yong-tao QU ; Xiu-ying LU ; Chun-guang SHAN ; Qing-jia SUN
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2012;47(4):330-333
OBJECTIVETo detect the expression of hypoxia inducible factor 1 alpha (HIF-1α), glucose transporter protein-1 (GLUT-1) and vascular endothelial growth factor (VEGF) in human laryngeal carcinoma tissue, and to study the relationship between hypoxia and HIF-1α, GLUT-1, VEGF in human laryngeal carcinoma Hep-2 cells and to explore the effect of HIF-1α, GLUT-1 and VEGF as endogenous hypoxic markers on laryngeal carcinoma.
METHODSThe expression levels of HIF-1α, GLUT-1 and VEGF were detected in 35 cases of laryngeal carcinoma by SP immunohistochemical methods and in Hep-2 cells by SP immunocytochemical methods. The relationship between HIF-1α and GLUT-1, VEGF protein expression was analyzed.
RESULTSOf the 35 cases, 16 cases expressed HIF-1α, 16 cases expressed GLUT-1, 19 cases expressed VEGF. The expression of HIF-1α and VEGF were closely correlated with pathologic grading and lymphnode metastasis. GLUT-1 was correlated with lymphnode metastasis. The expression levels of HIF-1α, GLUT-1 and VEGF in Hep-2 cells under hypoxic condition were higher than those under normoxic condition.
CONCLUSIONHIF-1α may promote the expression of GLUT-1 and VEGF in laryngeal carcinoma, furthermore promote tumor angiogenesis, invasion, and metastasis of the laryngeal carcinoma.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Female ; Glucose Transporter Type 1 ; metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Vascular Endothelial Growth Factor A ; metabolism
6.Sequence analysis of the connexin 26 genes from a deafness family with A1555G mutation in Huaiyin.
Hai-Jun ZHANG ; Chun-Hong XU ; Yi-Ju ZHANG ; Su-Ying ZHAO ; Xue-Xia GENG ; Yun-Feng SHAN ; Gang FAN ; Guang-Qian XING ; Xiang-Nian SHAN ; Xing-Kuan BU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2005;40(9):678-683
OBJECTIVETo ascertain whether connexin 26 (Cx26) gene was a nuclear modifier gene in an extensive family with matrilineal nonsyndromic deafness associated with A1555G mutation in Huaiyin, China.
METHODSFollowing PCR-restriction fragment length polymorphism (PCR-RFLP) with ApaI restriction enzyme, Cx26 genes from 26 cases, with A1555G mitochondrial mutations in this family, and 62 controls (including 2 patrilineal relatives, 10 spouse controls and 50 unrelated controls), were sequenced.
RESULTSCompared with the reference sequence of Cx26 gene, totally four kinds of nucleotide changes,79G -->A, 109G-->A, 341G-->A and 235delC, were detected in a heterozygous form. However, the former three were previously reported polymorphisms, and only the 235delC was a previously described recessive mutation associated with most autosomal nonsyndromic sensorineural hearing loss in Japan and China. Further study showed that the heterozygous 235delC mutation existed in both one individual with mild hearing loss and two individuals with normal hearing. Clinical characterization showed that 235delC mutation did not seem to modify the deafness phenotype due to the A1555G mutation. Moreover, this 235delC mutation was deduced to derive from a married-in control. Finally, there were no co-segregation between the phenotypes of hearing loss and the genotypes for Cx26 genes based on the four kinds of nucleotide changes.
CONCLUSIONSThe heterozygous 235delC mutation of the Cx26 gene may not modulate the severity of hearing loss associated with A1555G mutation and Cx26 gene is unlikely to be a modifier gene for hearing loss due to A1555G mitochondrial mutation in this Chinese family.
Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; Deafness ; epidemiology ; ethnology ; genetics ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mutation ; Pedigree ; Phenotype ; Polymorphism, Restriction Fragment Length ; Sequence Analysis ; Young Adult
7.Distribution of chromium in whole blood and urine among general population in China between year 2009 and 2010.
Chun-guang DING ; Ya-juan PAN ; Ai-hua ZHANG ; Bang-hua WU ; Han-lin HUANG ; Chun ZHU ; De-ye LIU ; Bao-li ZHU ; Guang XU ; Hua SHAO ; Shan-zhuo PENG ; Xian-long JIANG ; Chun-xiang ZHAO ; Chang-cheng HAN ; Hong-rong JI ; Shan-fa YU ; Xiao-xi ZHANG ; Long-lian ZHANG ; Yu-xin ZHENG ; Hui-fang YAN
Chinese Journal of Preventive Medicine 2012;46(8):679-682
OBJECTIVETo evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.
METHODSFrom year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.
RESULTSAmong general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.
CONCLUSIONThe study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.
Adolescent ; Adult ; Child ; China ; Chromium ; blood ; urine ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Young Adult
8.A research on prevalence and risk factors of type 2 diabetes mellitus in the farmers and immigrants of Yi people in Liangshan, Sichuan province, China.
Bin WANG ; Da-Ying WEI ; Chun-Xiu WANG ; Jian-Hua ZHANG ; Li PAN ; Ming-Ju MA ; Fang XUE ; Guang-Liang SHAN
Chinese Journal of Preventive Medicine 2010;44(6):510-515
OBJECTIVETo explore the difference on the prevalence and the risk factors of type 2 diabetes(T2DM) between Yi farmer and immigrants in Liangshan, Sichuan province.
METHODSA representative sample of 2878 Yi people (including 1549 farmers and 1329 immigrants) aged from 16 to 76 was selected by the method of multistage and cluster sampling in Liangshan, Sichuan province, China, during 2007 - 2008. The samples were divided into 5 groups by the factor of age (16-, 25-, 35-, 45- and 55-76). The standardized prevalence of T2DM was calculated by the national census data in 2000. Logistic regression analysis was used to study the related risk factors of T2DM.
RESULTSThe prevalence of Yi farmer was 4.33% (67/1549) (male: 6.15% (42/683), female: 2.89% (25/866)), and that of Yi migrants was 9.03% (120/1329) (male: 11.31% (88/778), female: 5.81% (32/551)). The standardized prevalence (SP) was calculated by the data of national census 2000. The SP of Yi farmer was 5.97%in male, and that of the female was 2.40%. The SP of Yi migrant was 10.25% in male, and that of the female was 6.29%. For Yi people, sex (male versus female, OR = 1.69, 95%CI: 1.02 - 2.81), age (versus the group aged 16- and 25-, group aged 35 to 54: OR = 5.04, 95%CI: 2.93 - 8.69; group aged above 54: OR = 6.19, 95%CI: 3.23 - 11.86), hypertension (versus normal group, borderline hypertension value: OR = 1.61, 95%CI: 1.08 - 2.38; hypertension group: OR = 2.40, 95%CI: 1.37 - 4.22), smoking (OR = 1.55, 95%CI: 1.01 - 2.37), triglyceride (TG) level (OR = 1.65, 95%CI: 1.10 - 2.46) and high-density lipoprotein cholesterol (HDL-C) level (OR = 1.64, 95%CI: 1.13 - 2.37) were the positive factors correlated with T2DM, and drinking (the alcohol volume from 22.67 to 52.50 g/d ) was negative factor (OR = 0.53, 95%CI: 0.30 - 0.95) correlated with T2DM.
CONCLUSIONThe prevalence of T2DM in Yi immigrants was higher than that in Yi farmers;sex, age, blood pressure, smoking, TG, HDL-C, drinking were influencing factors of T2DM.
Adolescent ; Adult ; Aged ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Ethnic Groups ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Rural Population ; Young Adult
9.Effect of single dose irradiation to parotid gland on the structured and function changes of bilateral parotid glands in miniature pig.
Zhao-chen SHAN ; Jun LI ; Guang-fei OU ; Xiao-yong LIU ; Chun-mei ZHANG ; Song-ling WANG
West China Journal of Stomatology 2006;24(1):83-88
OBJECTIVETo evaluate the effects of a solitary megadose protocol of ionizing radiation (IR) to parotid gland on the structured and function changes of bilateral parotid glands in miniature pig.
METHODSFourteen minipigs were subjected to either 15 or 20 Gy to one parotid gland with a linear accelerator, while another four minipigs served as non-IR controls. Salivary flow rates and salivary chemistries were measured pre-IR, and 4 and 16 weeks post-IR. A quantitative assessment of gland weight and acinar area, and detailed serum chemistry and hematological analyses, were also performed.
RESULTSParotid gland weights were significantly decreased in the 15 and 20 Gy groups at 4 and 16 weeks post-IR. The acinar cell area in glands of both IR groups was significantly reduced. Parotid flow rates decreased by 60% with 15 Gy at 16 weeks post-IR. In the 20 Gy group, salivary flow rates were reduced by 80% at 16 weeks post-IR. Additionally, parotid flow rates significantly reduced in contralateral glands with 20 Gy at 16 weeks, while structure and weight did not changes in parotid glands.
CONCLUSIONStructural changes in salivary gland parenchyma occurred relatively early after IR, while the alterations in salivary output were relatively delayed. Further, reductions in salivary flow were not proportional to acinar cell area loss. There isn't a significant structured change of contralateral glands, but significant reduction of parotid flow rate at this time.
Animals ; Parotid Gland ; radiation effects ; Swine ; Swine, Miniature
10.Synthesis and antiviral activities of geldanamycin analog TC-GM in vitro.
Chun-Xin LI ; Guang-Zhi SHAN ; Bo FAN ; Pei-Zhen TAO ; Li-Xun ZHAO ; Jian-Dong JIANG ; Yu-Huan LI ; Zhuo-Rong LI
Acta Pharmaceutica Sinica 2011;46(6):683-687
In order to find antiviral compounds with novel structures, geldanamycin and lamivudine with different antiviral mechanisms were conjunctively synthesized to acquire a new compound TC-GM, and the antiviral activity of TC-GM was measured. The antiviral activity against HIV-1 was examined by p24 antigen ELISA kit. The activity against HBV was examined by dotblot. The activity against HSV and CoxB virus was examined by CPE. TC-GM exhibited broad-spectrum antiviral activities similarly like geldanamycin. TC-GM inhibited the replication of different viruses, including HIV-1, HBV, HSV 1 and 2, CoxB6. TC-GM showed more potent inhibitory activity against HIV-1 and HBV than other detected virus.
Animals
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Anti-HIV Agents
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chemical synthesis
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chemistry
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pharmacology
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Antiviral Agents
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chemical synthesis
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chemistry
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pharmacology
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Benzoquinones
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chemical synthesis
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chemistry
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pharmacology
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Cell Line, Tumor
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Cercopithecus aethiops
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Enterovirus B, Human
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drug effects
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physiology
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HIV-1
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drug effects
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physiology
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Hep G2 Cells
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Hepatitis B virus
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drug effects
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physiology
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Herpesvirus 1, Human
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drug effects
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physiology
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Herpesvirus 2, Human
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drug effects
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physiology
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Humans
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Lactams, Macrocyclic
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chemical synthesis
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chemistry
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pharmacology
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Lamivudine
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chemical synthesis
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chemistry
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pharmacology
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Madin Darby Canine Kidney Cells
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
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pathology
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virology
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Vero Cells
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Virus Replication
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drug effects