1.Efficacy and side effects of combination therapy of oxaliplatin and S-1 for colorectal cancer.
Chinese Journal of Oncology 2011;33(5):388-390
OBJECTIVETo observe the efficacy and side effects of the combination therapy of oxaliplatin and S-1 in treating postoperative colorectal cancer patients.
METHODS54 postoperative colorectal cancer patients received the combination therapy of oxaliplatin and S-1 regimen, repeated every 3 weeks, and evaluate the efficacy after 3 cycles.
RESULTSAll of the 54 patients but 2 (changed the chemotherapy regimen after the first cycle because of economic reason) finished 6 cycles of the chemotherapy treatment. There were 6 cases (11.5%) with complete response (CR), 28 cases (53.8%) with partial response (PR), and the overall response rate was 65.4%. Major adverse effects were hematological toxicities, gastrointestinal disturbance, neurosensory toxicity. There were no chemotherapy-related deaths.
CONCLUSIONSOxaliplatin combined with S-1 is an effective and better tolerated chemotherapy treatment for postoperative colorectal cancer patients, with no serious side effects for liver and kidney. Therefore, it can be used as an alternative chemotherapy regimen for postoperative colorectal cancer patients.
Adenocarcinoma ; drug therapy ; surgery ; Adenocarcinoma, Mucinous ; drug therapy ; surgery ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Colonic Neoplasms ; drug therapy ; surgery ; Diarrhea ; chemically induced ; Female ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Postoperative Period ; Pyridines ; administration & dosage ; adverse effects ; Rectal Neoplasms ; drug therapy ; surgery ; Remission Induction ; Tegafur ; administration & dosage ; adverse effects ; Vomiting ; chemically induced
2.Different metabolites of leaves between Tripterygium wilfordii and Tripterygium hypoglaucum based on UPLC-Q-TOF-MS.
Chao LIU ; Qing-xiu HAO ; Yan JIN ; Lu-qi HUANG ; Li-ping KANG ; Lan-ping GUO
China Journal of Chinese Materia Medica 2015;40(9):1710-1717
To analysis the differences between Tripterygium wilfordii and T. hypoglaucum, specimens of their leaves were collected from five production regions and analyzed by ultra performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). The data were analyzed by multivariate statistical method, such as hierarchical cluster analysis (HCA) principal component analysis (PCA) and orthogonal signal correction partial least square discrimination (OPLS-DA). Potential markers with VIP values above 5.0 and corresponding r values above 0.85, were selected and further tested by combining mann-Whitney nonparametric. Those with P < 0.001 and AUC = 1 were confirmed as metabolite markers to discriminate them from each other. Results revealed that the two species were obviously different in their leaf metabolites. Based on their mass spectra, 23 potential metabolite markers were identified to distinguish T. wilfordii from T. hypoglaucum.
Chromatography, High Pressure Liquid
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Drugs, Chinese Herbal
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chemistry
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metabolism
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Mass Spectrometry
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Molecular Structure
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Plant Leaves
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chemistry
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metabolism
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Tripterygium
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chemistry
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classification
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metabolism
3.Construction of Saccharomyces cerevisiae haploid mutant deficient in lanosterol synthase gene.
Li-Li GAO ; Qing-Hua WANG ; Hui-Chao LIANG ; Ting GONG ; Jin-Ling YANG ; Ping ZHU
Acta Pharmaceutica Sinica 2014;49(5):742-746
Lanosterol synthase is encoded by the erg7 gene and catalyzes the cyclization of 2, 3-oxidosqualene, which is a rate-limiting step of the inherent mevalonate (MVA)/ergosterol metabolic pathway in Saccharomyces cerevisiae. The intermediate 2, 3-oxidosqualene is also the precursor of triterpenoids. Therefore, the cyclization of 2, 3-oxidosqualene is the key branch point of ergosterol and triterpenoids biosynthesis. Down-regulation of 2, 3-oxidosqualene metabolic flux to ergosterol in S. cerevisiae may redirect the metabolic flux toward the triterpenoid synthetic pathway reconstructed by the synthetic biology approach. To construct erg7 knockout cassette harboring the loxP-Marker-loxP element, long primers were designed, which were homologous to the sequences of both erg7 ORF and plasmid pUG66. The cassette was transformed into diploid wild strain INVSc1 by LiAc/SS Carrier DNA/PEG method and then erg7 gene haploid deficient mutant was obtained by homologous recombination. The results of semiquantitative PCR and real-time quantitative PCR revealed that erg7 expression level in erg7 gene haploid deficient mutant is one time lower than that in wild strain. The results of TLC and HPLC showed that the ergosterol content in deficient mutant decreased to 42% of that in wild strain.
Chromatography, High Pressure Liquid
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DNA Primers
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Down-Regulation
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Ergosterol
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metabolism
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Haploidy
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Intramolecular Transferases
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genetics
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Polymerase Chain Reaction
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Saccharomyces cerevisiae
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genetics
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Squalene
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analogs & derivatives
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metabolism
4.The basic strategies and research advances in the studies on glycosyltransferases involved in ginsenoside biosynthesis.
Hui-Chao LIANG ; Qing-Hua WANG ; Ting GONG ; Guo-Hua DU ; Jin-Ling YANG ; Ping ZHU
Acta Pharmaceutica Sinica 2015;50(2):148-153
Traditional herbal medicines, Panax ginseng, Panax quinquefolium and Panax notoginseng, attract our attention for their extensive and powerful pharmacological activities. Ginsenosides are the main active constituents of these medicinal herbs. The related glycosyltransferases involved in ginsenoside biosynthesis are the key enzymes which catalyze the last important step. Modification of ginsenoside aglycones by glycosyltransferases produces the complexity and diversity of ginsenosides, which have more extensive pharmacological activity. At present, ginsenoside aglycones and compound K have been obtained by synthetic biology. As the last step of ginsenoside biosynthesis, glycosylation of ginsenoside aglycones has been studied intensively in recent years. This review summarizes the basic strategies and research advances in studies on glycosyltransferases involved in ginsenoside biosynthesis, which is expected to lay the theoretical foundation for the in-depth research of biosynthetic pathway of ginsenosides and their production by synthetic biology.
Biosynthetic Pathways
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Ginsenosides
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biosynthesis
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Glycosyltransferases
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metabolism
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Panax
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chemistry
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Plants, Medicinal
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chemistry
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Synthetic Biology
5.Research advances of the influence factors of high level expression of recombinant protein in Pichia pastoris.
Qing-Hua WANG ; Li-Li GAO ; Hui-Chao LIANG ; Ting GONG ; Jin-Ling YANG ; Ping ZHU
Acta Pharmaceutica Sinica 2014;49(12):1644-1649
Pichia pastoris is one of the most important systems used in the field of molecular biology for the expression of recombinant proteins. The system has advantages of high expression, high stability, high secretion, easy high-density fermentation and low cost. Many factors affect the expression of recombinant protein, such as gene copy number, codon usage preference, type of promoter, molecular chaperones, glycosylation, signal peptide and fermentation process. In this review, research advances of the above aspects are summarized, which lay a foundation for improving the expression of recombinant proteins in P. pastoris.
Fermentation
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Gene Dosage
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Glycosylation
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Molecular Chaperones
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Pichia
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metabolism
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Promoter Regions, Genetic
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Protein Sorting Signals
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Recombinant Proteins
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biosynthesis
6.Key problems in development of molecular identification in traditional Chinese medicine.
Lu-Qi HUANG ; Yuan YUAN ; Qing-Jun YUAN ; Xiao-Hua JIN ; Wei ZHANG ; Dan QIAN ; Chao JIANG
China Journal of Chinese Materia Medica 2014;39(19):3663-3667
Molecular identification of Chinese traditional medicine has come from laboratory research into application, but there are some misunderstandings and problems emerging after rapid development. In this paper, we discuss the usage principle, hot field and technology innovation in molecular identification of Chinese traditional medicine. And molecular identification of traditional Chinese medicine has scientific and objective basis, follows the certain systematic research background, and adopts practical principles to establish case by case multi-class identification system. In order to achieve rapid, on-site, high throughput, low cost of traditional Chinese medicine identification purpose, molecular identification technology is further developing for meet the actual needs and the laboratory results further transformation in the service of traditional Chinese medicine industry.
China
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Drugs, Chinese Herbal
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chemistry
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standards
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Medicine, Chinese Traditional
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Plants, Medicinal
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chemistry
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classification
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genetics
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Quality Control
7.Downregulation of lanosterol synthase gene expression by antisense RNA technology in Saccharomyces cerevisiae.
Qing-hua WANG ; Li-li GAO ; Hui-chao LIANG ; Guo-hua DU ; Ting GONG ; Jin-ling YANG ; Ping ZHU
Acta Pharmaceutica Sinica 2015;50(1):118-122
The cyclization of 2,3-oxidosqualene is the key branch point of ergosterol and triterpenoid biosynthesis. Downregulation of 2,3-oxidosqualene metabolic flux to ergosterol in Saccharomyces cerevisiae may redirect the metabolic flux toward the triterpenoid synthetic pathway. In our study, primers were designed according to erg7 gene sequence of S. cerevisiae. Three fragments including 5' long fragment, 5' short fragment and erg7 coding region fragment were amplified by PCR. 5' long fragment consists of the promoter and a part of erg7 coding region sequence. 5' short fragment consists of a part of promoter and a part of erg7 coding region sequence. These fragments were inserted reversely into pESC-URA to construct antisense expression plasmids. The recombinant plasmids were transformed into S. cerevisiae INVSc1 and recombinant strains were screened on the nutritional deficient medium SD-URA. The erg7 expression level of recombinant strains, which harbored antisense expression plasmid of erg7 coding region, was similar to that of INVScl by semi-quantitative PCR detection. But erg7 expression level of recombinant strains, which harbored 5' long antisense fragment and 5' short antisense fragment, was significantly lower than that of the control. The results of TLC and HPLC showed that the ergosterol content of recombinant strains, which harbored 5' long antisense fragment, decreased obviously. The ergosterol contents of the others were almost equal to that of INVSc1. Lanosterol synthase gene expression was downregulated by antisense RNA technology in S. cerevisiae, which lays a foundation for reconstructing triterpenoid metabolic pathway in S. cerevisiae by synthetic biology technology.
DNA Primers
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Down-Regulation
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Gene Expression
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Intramolecular Transferases
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genetics
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metabolism
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Plasmids
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Polymerase Chain Reaction
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RNA, Antisense
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Saccharomyces cerevisiae
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enzymology
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genetics
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Squalene
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analogs & derivatives
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metabolism
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Transformation, Genetic
8.CT-guided stereotactic and neuroendoscope-assisted surgery for hypertensive cerebral hemorrhage
Chao-Qun WENG ; Jin-Dong ZHOU ; Qing-Dong JIN ; Huang LIN
Chinese Journal of Neuromedicine 2008;7(4):414-416
Objective To evaluate the curative effect of CT-guided stereotactic and neuroendoscope-assisted operation on cerebral hemorrhage caused by hypertension. Methods Twenty-five cases of cerebral hemorrhage caused by hypertension treated in our department in 2005-2006 were selected. ASA602A type position finder was installed under local anesthesia, and operation planning system was imported after CT scanning. The target point was selected at 1-1.5 cm posterior the central point of the largest hematoma, then the coordinate of the target point was calculated, and incisal opening and operation approach were programmed. Brain operation with trephine was performed under general anesthesia. After hematoma evacuating cannula were placed in the skull hole of 3 cm in diameter to remove partial hematoma, neuroendoscope was inserted to get rid of hematoma and stop bleeding.Results Of 25 patients with cerebral hemorrhage, 24 h after operation, 10 received evacuation of 60%-70% of hematomas, 11 did 80%-90%, 4 did more than 90%; 72 h after operation, all patients received evacuation of more than 90%. During the follow-up for 3 months after the operation, activities of daily living (ADL) scoring showed excellent improvement in 14 cases and amelioration in 9; 2 patients died from lung infection 10, 14 d after operation, respectively. Conclusions CT-guided stereotactic and neuroendoscope-assisted surgery is a safe, effective and minimally invasive method to treat hypertensive cerebral hemorrhage.
9.Research on syndrome distribution features, etiologies, and pathogeneses of Japanese encephalitis.
Jin-Wen TU ; Meng-Jiu DONG ; Zhi-Yong LIU ; Qing-Jing ZHU ; Chao-Min ZHU ; Li LI ; Hu WAN ; Ying LAN ; Yun LI ; Jun CHEN
Chinese Journal of Integrated Traditional and Western Medicine 2014;34(3):308-311
OBJECTIVETo explore Chinese medical syndrome distribution features of Japanese encephalitis (JE), and to analyze its correlation between syndromes and features of etiologies and pathogeneses.
METHODSRecruited were 277 patients with confirmative diagnosis of JE from Wuhan Medical Treatment Center, Children's Hospital Affiliated to Chongqing Medical University, Fifth People's Hospital of Guiyang City, Hangzhou Sixth People's Hospital, and Chengdu Hospital of Infectious Diseases between July to September 2012. Chinese medical syndrome distribution features were summarized from their general materials and detailed records of clinical data, including medical history, symptoms and signs, tongue fur, and pulse figures.The frequency of symptoms and signs was calculated according to mild, ordinary, severe, extreme severe degrees. The distribution of Chinese medical syndromes was summarized. And its correlation between syndromes and features of etiologies and pathogeneses were analyzed.
RESULTSAfter clustering analysis, Chinese medical syndromes of JE could be categorized as four groups: toxicity accumulation in Fei and Wei syndrome (TAFWS), brain collateral impaired by poison syndrome (BCIPS), depression of toxicity in the pericardium syndrome (DTPS), exhaustion of yin and yang syndrome (EYYS). BCIPS and DTPS were dominated, accounting for 74.0% (205 cases). The main causes covered evil of summer heat [accounting for 92.42% (256/277 cases)], heat [accounting for 87.73% (243/277 cases)], and toxin [accounting for 99.64% (276/277 cases)].
CONCLUSIONSThe four Chinese medical syndrome types of JE met Chinese medical clinical features of encephalitis. It is induced by infestation of dampness-heat, resulting in toxicity accumulation in Fei and Wei, brain collateral impaired by poison, depression of toxicity in the pericardium. Yin fluid and blood is exhausted as time goes by. Qi and yin are impaired to form intermingled deficiency and excess, and finally causing exhaustion of yin and yang.
Adolescent ; Child ; Child, Preschool ; Encephalitis, Japanese ; diagnosis ; pathology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Medicine, Chinese Traditional ; methods ; Yang Deficiency ; diagnosis ; Yin Deficiency ; diagnosis
10.Comparative pharmacokinetic analysis based on nonlinear mixed effect model.
Lu-jin LI ; Xian-xing LI ; Ling XU ; Ying-hua LÜ ; Jun-chao CHEN ; Qing-shan ZHENG
Acta Pharmaceutica Sinica 2011;46(4):447-453
Comparative pharmacokinetic (PK) analysis is often carried out throughout the entire period of drug development, the common approach for the assessment of pharmacokinetics between different treatments requires that the individual PK parameters, which employs estimation of 90% confidence intervals for the ratio of average parameters, such as AUC and Cmax, these 90% confidence intervals then need to be compared with the pre-specified equivalent interval, and last we determine whether the two treatments are equivalent. Unfortunately in many clinical circumstances, some or even all of the individuals can only be sparsely sampled, making the individual evaluation difficult by the conventional non-compartmental analysis. In such cases, nonlinear mixed effect model (NONMEM) could be applied to analyze the sparse data. In this article, we simulated a sparsely sampling design trial based on the dense sampling data from a truly comparative PK study. The sparse data were analyzed with NONMEM method, and the original dense data were analyzed with non-compartment analysis. Although the trial design and analysis methods are different, the 90% confidence intervals for the ratio of PK parameters based on 1000 Bootstrap are very similar, indicated that the analysis based on NONMEM is a reliable method to treat with the sparse data in the comparative pharmacokinetic study.
Area Under Curve
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Confidence Intervals
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Humans
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Nonlinear Dynamics
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Pharmacokinetics
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Sampling Studies