1.Evidence-based Research on the Chinese Precision Medicine Concept
Bin WU ; Mei ZHAN ; Ting XU ; Qiaozhi HU ; Fangyuan TIAN
China Pharmacy 2017;28(8):1017-1022
OBJECTIVE:To investigate the concepts and contents of the Chinese precision medicine,and to provide reference for the development of precision medicine in China.METHODS:By evidence-based evaluation method,using jingzhun yixue jingzhun yiliaoprecision medicineas keywords,all literatures were retrieved from CBM,CNKI,Wanfang,VIP,PubMed and Ovid EMBase databases up to Nov.17th,2015.The relevant information were extracted,including researchers (first author or correspondence author's unit belonged to China),domains and concepts.The concepts and contents of the Chinese precision medicine based on China's national condition were summarized and analyzed,and the difference between precision medicine and personalized medicine was compared.RESULTS:54 studies were included,the results indicated most studies (51 literatures) were published in 2015 by hospitals (28 literatures) and high schools (14 literatures);most literatures (23 literatures) presented the concept of precision medicine,followed by disease precision medicine (19 literatures) and relevant technology of precision medicine (7 literatures);a total of 39 literatures presented the specific concept of precision medicine.Besides genetic information involved in American precision medicine,the Chinese one expanded the disease diagnosis and treatment technology,as well as the application.Personalized medicine and precision medicine were in common partially,however,the latter one underlined the disease classification and diagnosis,which was more practicable.CONCLUSIONS:Chinese precision medicine involves disease diagnosis and treatment technology as well as influential factors based on genetic information,and includes disease classification and diagnosis so as to perform personalized precision intervention.The Chinese precision medicine is overall developed and focused.
2.Impact of CYP2C19 polymorphisms on eradication of Helicobacter pylori using triple therapy with esomeprazole
Lei ZHANG ; Jianming XU ; Qiao MEI ; Qiusen LI ; Yongmei HU
Chinese Journal of Digestion 2009;29(9):545-548
Objective To prospectively compare the efficacy of omeprazole and esomeprazole on H. pylori eradication related to cytochrome P450 (CYP) 2C19 polymorphism in Chinese Han poputafion. Methods A total of 240 patients with peptic ulcer were randomly assigned to receive either EAC (amoxicillin, clarithromyein and esomeprazole) treatment or OAC (amoxicillin, clarithromycin and orneprazole) treatment for one week with 120 each. Then, the patients were sustained treated with esomeprazol or omeprazole for 3 weeks. The endoscopic evaluation was performed 2 weeks after treatment. At the end of the treatment, a carbon-13 (13C) urea breath test (13C-UBT) was performed to determine H. pylori status. Polymerase chain reaction and restriction fragment length polymorphism were used to detect CYP2C19 genotypes including extensive metabolizer (EM), poor metabolizer (PM), homozygous (homEM) and hetEM. Results Two hundred and twenty five of 240 patients completed the study. H. pylori eradication was 79.2% with OAC regimen and 88.3% with EAC regimen by intention to-treat (ITT) analyses without difference (P>0.05). Whereas H. pylori eradication was 87.20/00 with OAC regimen and 91.4% with EAC regimen by per-protocol (PP) analyses without difference (P>0. 05). However, both ITT and PP analysis showed that there was significant difference in H. pylori eradication between EAC regimen (91.9% and 97.1%) and OAC regimen (71.8% and 77.8%) in patients with homEM genotype (P= 0.037 and P=0.028). Two weeks after treatment, the percentage of ulcer healing was 79.2% or 81.9% in EAC group and 69.2% or 76.1% in OAC group by ITT or PP analysis, respectively (P> 0.05). Low side effects were noted in EAC or OAC groups (3.3% vs. 7.5%,P>0.05). Conclusion The high eradication will be achieved by esomeprazole-based triple regimen which is superior to omeprazole-based triple regimen in treatment of patients with homEM genotype.
3."PEG dilemma" for liposomes and its solving approaches.
Di ZHANG ; Huan XU ; Mei-na HU ; Yi-hui DENG
Acta Pharmaceutica Sinica 2015;50(3):252-260
Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents
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chemistry
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Drug Carriers
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chemistry
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Liposomes
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chemistry
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Polyethylene Glycols
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chemistry
4.Dosimetry of conformal radiotherapy, field-in-field intensity-modulated radiotherapy, and inverse-planned intensity-modulated radiotherapy after breast-conserving surgery for left-sided breast cancer: a comparative analysis
Wen HUO ; Bo NING ; Jing HU ; Mei XU ; Gang LIU
Chinese Journal of Radiation Oncology 2016;25(7):745-747
Objective To investigate the differences in dosimetry between conformal radiotherapy (CRT),field-in-field intensity-modulated radiotherapy (FIF-IMRT),and intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer.Methods A total of 31 patients who underwent breast-conserving surgery for left-sided breast cancer were randomly selected,and the plans for CRT,FIF-IMRT,and IMRT were developed.The dose-volume histogram (DVH) was used for self-control study,and the non-parametric test was used to compare the differences in target volume and doses to organs at risk (OARs).Results All the three methods met the requirements of the prescribed doses.The CRT group had a higher V105 of the target volume and higher heart V30 and Dmax (P=0.000,0.000,0.000).The IMRT group had higher V5 and Dmean (P=0.000,0.000),as well as a higher lung V5 and a lower lung V40 (P=0.000,0.000).The FIF-IMRT group had the lowest Dmean (P=0.000),and the IMRT group had significantly higher Dmean and Dmax of the right lung and the spinal cord than the other two groups (P=0.000,0.000,0.000,0.000).The FIF-IMRT group had a significantly lower single hop count than the other two groups (P=0.000).Conclusions CRT has a good dose distribution in the target volume,but greatly injures the surrounding tissues.FIF-IMRT can well protect OARs and cause less damage to the device.
5.Topiramate monotherapy for alcohol dependence:a meta-analysis
Qiaozhi HU ; Mei ZHAN ; Ling WANG ; Ting XU
Chinese Journal of Nervous and Mental Diseases 2015;(6):349-354
Objective To assess the efficacy and safety of topiramate monotherapy in the treatment of alcohol de?pendence. Methods The Cochrane library, PunMed, EMBase, CNKI, VIP and CBM database were searched to collect the randomized contolled trials (RCTs) of topiramate monotherapy to compare with placebo or positive control drug in al?cohol dependence. Data were extracted from the included literatures after the literatures’qualities were assessed. The meta-analyses were conducted with RevMan 5.2 software. Results Thirteen trials were included. Compared with place?bo, topiramate reduced score of obsessive compulsive drinking scale(MD=-5.90,95%CI:-10.99~-0.82,P=0.02), de?creased drinks per drinking day(MD=-6.94,95%CI:-12.20~-1.68,P=0.01), and increased percentage of days absti?nent(MD=15.36,95%CI:4.15~6.56,P<0.01). The incidence of paraesthesia, taste perversion, weight loss, memory or concentration impairment, dizziness, psychomotor retardation in topiramate group was higher. But the incidence of other adverse events was similar between groups. Compared with naltrexone, topiramate significantly postponed the days to first relapse(MD=2.10,95%CI:0.23~3.97,P=0.03). The adverse events were similar between groups. Conclusions Topira?mate in treatment of alcohol dependence is effective and safety.
6.Vector flow mapping in quantitative assessment of regional myocardial function in patients with coronary artery disease
Mingjun XU ; Mei ZHANG ; Xiaobo HU ; Yun ZHANG
Chinese Journal of Ultrasonography 2013;22(9):741-746
Objective To investigate blood flow dynamics adjacent to regional myocardial segments in coronary artery disease(CAD) patients and to explore the association of the two CAD features.Methods In 43 CAD patients,velocity vector imaging (VVI) was used to evaluate the wall motion and classify normal myocardial segments (NS),relatively abnormal and obviously abnormal wall motion segments (RS and OS) by systolic peak strain (Ss).Vector flow mapping (VFM) was used to show blood flow dynamics in the heart chamber,including blood flow (Q) heading towards or away from the apex during a heart beat and time to every peak flow (T).Results Compared with NS,both RS and OS showed a higher systole Q + (blood flow heading towards the apex during systole) and lower diastole Q + (blood flow heading towards the apex during diastole) and shortened T2 (adjusted time interval between E and A peaks).Systole Q + was positively correlated with Ss but negatively with segmental ejection fraction (SEF).Diastole Q + was negatively correlated with early and late diastolic peak velocity (Ve and Va) but positively with Ve/Va.T2 was negatively correlated with Ve but positively with Ve/Va and early diastolic peak strain rate (SRe).Conclusions VFM might be a new tool to quantitatively assess change in regional blood flow dynamics in patients with CAD.
7.Study on the action mechanism for δ-tocotrienol-induced apoptosis of human hepatoma HepG2 cells
Zhongquan ZHANG ; Mei XU ; Guoqiang HU ; Songqiang XIE
Tumor 2010;(3):184-187
Objective:To elucidate action mechanism of δ-tocotrienol in inducing apoptosis of human hepatoma HepG2 cells. Methods:Cell proliferation and viability were assessed by MTT assay; cell cycle distribution, apoptotic rate and mitochondrial membrane potential were measured by using high content screening system; the expression of apoptosis-related protein such as caspase-3, caspase-8, caspase-9, Bcl-2, Bax, tBid and cytochrome C in the HepG2 cells were evaluated by Western blotting. Results:δ-Toco-trienol inhibited HepG2 cell proliferation and induced apoptosis in a dose-dependent manner. This growth-inhibiting effect of δ-toco-trienol correlated with loss of mitochondrial membrane potential and release of cytochrome C from mitochondria to cytoplasm, and regulation of the protein expression of Bcl-2 family members, such as up-regulation of Bax and tBid and down-regulation of Bcl-2. Subsequently tocotrienol induced the activation of caspase-3, caspase-8, and caspase-9 which finally induced apoptosis of hepatoma HepG2 cells. Conclusion:δ-Tocotrienol induced apoptosis of human hepatoma HepG2 cells via mitochondrial pathway and membrane death receptor pathway.
8.Effect of melatonin on colon immunological function during colitis in rats
Qiao MEI ; Li XIANG ; Zonghao ZHAO ; Yongmei HU ; Jianming XU
Chinese Journal of Pathophysiology 1986;0(03):-
AIM: To investigate the effects of melatonin (MT) on the immunological function in colon of rats immunological colitis. METHODS: The rats colitis was produced by enema with trinitrobenzene sulfonic acid and ethanol. The experiment groups included normal group, model group, 5-aminosalicylic acid (5-ASA) group (100 mg?kg~(-1)), MT groups (2.5,5.0,10.0 mg?kg~(-1)), and treated intracolon with saline, saline, 5-ASA and MT respectively (once per day, from the d7 after the establishment of colitis model to the end of the experiment). The content of interleukin (IL-1, IL-2) and tumour necrosis factor (TNF)-? in rats colon were detected; The inflammatory colon were homogenatized and incubated with lipopolysaccharides (LPS), and designed as control group, model group, 5-ASA group (100?mol/L), MT groups(0.01, 0.1, 1.0 mmol/L). The content of IL-1, IL-2, TNF-?, nitric oxide (NO), lactic dehydrogenase (LDH), myeloperoxidase (MPO) and malondiadehyde (MDA) in the supernant were detected. RESULTS: In model group, the contents of IL-1, IL-2 and TNF-? in colon elevated remarkably and MT depressed this effectively. In the inflammatory colon homogenates of rats colitis, the content of IL-1, IL-2, TNF-?, NO, LDH, MPO and MDA elevated remarkably, Pretreation with MT depressed the content of IL-1, TNF-?, LDH, MPO and MDA effectively. MT (1.0mmol/L) also reduced the production of NO obviously. CONCLUSION: The abnormal immunological function is shown obviously in rats colitis. MT normalizes this change in vivo and in vitro and attenuates the mucosal damage.
9.Effects of cytochrome P450 2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of rabeprazole in Chinese
Jianming XU ; Yongmei HU ; Qiao MEI ; Al ET ;
Chinese Journal of Digestion 2001;0(10):-
4 time percentage of 24 h were observed among the three different genotype groups after a single dose or repeated doses of rabeprazole. And the ratio of these pH dates between day 1 and day 8 ranged from 85% to 110%.Conclusions In Chinese healthy Han people, CYP 2C19 genetic polymorphism has not any significant influence on acid inhibitory efficacy and the metabolism of rabeprazole. Rebeprazole could rapidly achieved maximum acid inhibitory efficacy in the subjects with different CYP2 C19 genotype status.
10.Antitumor mechanism of HG251,a novel anthracene derivative,in K562/DOX leukemia cells
Zhongquan ZHANG ; Mei XU ; Songqiang XIE ; Guoqiang HU ; Biansheng JI
Chinese Pharmacological Bulletin 2003;0(10):-
Aim To evaluate the mechanism of HG251-induced apoptosis in K562/DOX cells.Methods Cell viability was assessed by MTT assay;cell cycle distribution,apoptosis and mitochondrial membrane potential were measured by flow cytometry;the protein expressions of P-gp,caspase-3,caspase-8,caspase-9,p53,Bcl-xL and cytochrome c in the K562/DOX cells were evaluated by Western blot.Results HG251 was able to inhibit cells proliferation,induce apoptosis,lose mitochondrial membrane potential,activate caspase-3,caspase-8,caspase-9,up-regulate p53 protein and down-regulate Bcl-xL protein in a dose-dependent manner but it had no effect on P-gp protein expression.Conclusion HG251 could overcome apoptotic resistance via up-regulating p53 protein and down-regulating Bcl-xL protein.In addition,HG251 also induced K562/DOX cells apoptosis via mitochondrial pathway and membrane death receptor pathway.