Objective To analyze literatures reported allele frequencies of CYP2C191,2,3 for healthy Asian populations, and to provide evidence-based data for further personalized drug therapy and pharmacogenomics research. Methods Relevant articles were electronically retrieved from digital databases of PubMed, EMbase, The Cochran Library, CNKI, WanFang Data, VIP and CBM, and the articles reporting the allele frequencies of CYP2C19 were included. According to the inclusion and exclusion criteria, the data of the allele frequencies of the gene were extracted, pooled, and analyzed. Results A total of 41 articles were included, involving 9 841 healthy Asians from 17 countries. Analyses were conducted according to regional features, based on China, East Asia (China, Korea and Japan), Southeast Asia (Vietnam, Thailand, Malaysia, Singapore, Myanmar, Indonesia and Philippines), South Asia (India), and West Asia (Palestine, Lebanon, Saudi Arabia, Turkey, Iranian and Jordan). The major results showed that the allele frequencies of CYP2C191,2,3 were 61.3%, 32.1% and 6.6% (Chinese, n=4170); 61.0%, 31.2% and 7.8% (East Asians, n=5879); 67.6%, 28.8% and 3.7% (East South Asians, n=1985); 64.0%, 35.2% and 0.8% (South Asians, n=679); and 87.3%, 12.1% and 0.6% (West Asians, n=1298), respectively. Based on the included 9841 healthy Asians from 17 countries, the total allele frequencies of CYP2C191,2,3 were 66.0%, 28.4% and 5.5%, respectively. Conclusion The allele frequencies of CYP2C191,2,3 2 fairly differ in ethnic groups in China, as well as in regions in Asia. Besides, genetic variation is impacted by geographical factors such as regions and environment.
Objective To investigate the influence of CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms on warfarin dosages of patients after heart valve replacement. Methods A total of 133 patients undergoing heart valve replacement in the Department of Cardiovascular Surgery of Fujian Provincial Hospital from November 2011 to August 2012 were included in this study. Polymerase chain reaction（PCR）gene sequencing was performed to detect CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphism of these 133 patients. Patients were grouped according to their genotypes，and average warfarin dosages were compared between different genotype groups. Results The frequencies of CYP2C9 3 AA，AC and CC were 127 patients，6 patients and 0 patient respectively，and average daily warfarin dosages were 3.75 mg and 2.13 mg respectively which were statistically different between differentCYP2C9 3 genotypes （P＜0.05）. The frequencies of VKORC1-1639 G＞A GG，GA and AA were 3 patients，32 patientsand 98 patients respectively，and average daily warfarin dosages were 6.00 mg，4.50 mg and 3.00 mg respectively which were statistically different between different VKORC1-1639 G＞A genotypes （P＜0.05）. The frequencies of CYP4F2 rs 2108622 CC，CT and TT were 67 patients，59 patients and 7 patients respectively，and average daily warfarin dosages were 3.00 mg，3.75 mg and 4.50 mg respectively which were statistically different between different CYP4F2 rs2108622 genotypes（P＜0.05）. Conclusion CYP2C9 3，VKORC1-1639 G＞A and CYP4F2 rs2108622 genetic polymorphisms are associated with individual difference of warfarin dosages of patients after heart valve replacement.
Objective To explore the effects of mechanical stretch with variant frequencies on the alignment and differentiation of the multilayer myotubes cultured in vitro, and to select the optimized cultural condition of regenerative skeletal muscle tissue with stress loading cultured in vitro. Methods C2C12 myoblasts cultured in vitro in the groove casts of Sylgard 184 were induced into the multilayer myotubes. Meanwhile the myoblasts were treated with various mechanical stretch withcells tensile instrument, at the amplitude of 10% and the frequency of 0 (group A), 0.25 (group B), 0.50 (group C), and 1.00 Hz (group D) for 1 hour, 3 times a day. The myotubes morphology was observed by inverted phase contrast microscope at 5, 7, and 10 days after continuous mechanical stretch. And the expressions of mRNA for myogenic differentiation antigen (MyoD), Myogenin, Desmin, and myosin heavy chain (MyHC) were detected by RT-PCR and real-time fluorescent quantitative PCR (QRT-PCR), respectively. Results The mechanical stretch could promote the al igned fusion and increase the number of myotubes. Indeed the multilayer myotubes arranged more closely in group B at 7 days. At the same group, as the time went on, the mRNA expressions of MyoD gradually decl ined in each group. There were significant differences in mRNA expressions of MyoD between 5 days and 7, 10 days (P lt; 0.05). The mRNA expressions of Myogenin, Desmin, and MyHC were highest at 7 days. There were significant differences between different time points (P lt; 0.05), except the mRNA expression of Desmin of group B between 7 and 10 days (P gt; 0.05). At the same time, with the increase of frequency, the highest mRNA expressions of MyoD, Myogenin, Desmin, and MyHC were in group B. There were significant differences at the same time between group B and the other groups (P lt; 0.05), except mRNA expression of Desmin at 5 days between groups B and C, and mRNA expression of MyHC at 10 days between groups A and B (P gt; 0.05). Conclusion Low frequency (0.25 Hz) and suitable time (7 days) periodic mechanical stretch is beneficial to the differentiation of the multilayer myotubes cultured in the groove casts of Sylgard 184, but as the stretch time goes on the aging of myotubes will be accelerated.
Objective To systematically evaluate anti-platelet effect of clopidogrel influenced by CYP2C192,3 polymorphism in patients with cardiovascular diseases, in order to provide references for its safe medication. Methods Literature was retrieved in electronic databases covering EMbase, PubMed, The Cochrane Library, CBM and CNKI from establishment dates to November, 2011. Observational studies and clinical trials were included, cross-checked, assessed and pooled for meta-analysis. meta-analysis was performed using the software RevMan 5.1. Results A total of 13 articles including 14 trials (n=36 855) were included. The results of meta-analysis showed that: a) there was no significant difference in the incidences of cardiovascular events between CYP2C192,3 carriers and CYP2C191 carriers; b) the risk of stent thrombosis in CYP2C192,3 carriers was significantly higher than that in CYP2C191 carriers (Plt;0.000 1), and the relative risk of CYP2C192,3 carriers increased 92% within one month (Plt;0.000 1); c) as for bleeding events, there were no significant differences between CYP2C192,3 carriers and CYP2C191 carriers. Conclusion Compared with CYP2C191 carriers, CYP2C192,3 carriers have a higher risk of stent thrombosis in clopidogrel-treated patients, but there are few differences in cardiovascular and bleeding events between the two carriers. Therefore, CYP2C192,3 carriers with cardiovascular diseases and ready to receive PCT are suggested to pay more attention to stent thrombosis when using clopidogrel. We propose that patients with cardiovascular diseases and ready to receive PCT should have CYP2C19 tests to determine the use of antiplatelet drug (clopidogrel) to avoid thrombus.
ObjectiveTo optimize HSP65-MUC1 fusion protein purification in pilot scale through protein purification techniques and identify the methods for biological activity detection. MethodsE. coli expressing HSP65-MUC1 was obtained by fermentation, then homogenized to obtain the supernatant. To acquire high-purity, high-quality HSP65-MUC1, the supernatant was treated with saturated ammonium sulfate, phenyl sepharose FF column and Q FF ion-exchange chromatography column purification. The expression of CD86 on the surface of DC cells treated with HSP65-MUC1 was determined with flow cytometry. ResultsE. coli containing pET28a-HSP65-MUC1 recombinant plasmid can effectively express target protein. A total of 413.7 mg of HSP65-MUC1 was obtained after 10 g of fermented cells was treated with saturated ammonium sulfate, phenyl sepharose FF column and Q FF ion-exchange chromatography column, and the purity was nearly 96%. Compared with negative control (10.13%±0.89%), purified HSP65-MUC1 could significantly improve the expression of CD86 on the surface of DC cells (29.98%±1.02%). ConclusionThe pilot scale production of purified HSP65-MUC1 has been effectively optimized, and the methods of its biological activity detection have been identified, which simultaneously provides the basis for clinical studies.
ObjectiveTo investigate MUC1 over-expression on chemotherapy of 5-fluorouracil and cisplatin for esophageal cancer cells. MethodsMUC1 over-expression and stable silencing of MUC1 expression esophageal cancer cell lines were constructed. Xenograft model of esophageal cancer was established in nude mice. Cisplatin (8 mg/kg, day 1 and day 7)and 5-fluorouracil (20 mg/kg, day 1 to 6)were injected intraperitoneally. Tumor volume and body weight of nude mice were measured. Tumor growth curve and body weight curve were drawn, and tumor inhibitory rate was calculated. ResultsBoth cisplatin and 5-fluorouracil suppressed tumor growth of MUC1 over-expression esophageal cancer nude mice. Body weight and tumor volume of nude mice of cisplatin and 5-fluorouracil groups were significantly smaller than those of the control group (P < 0.05), and the inhibitory effects of cisplatin were significantly greater than those of 5-fluorouracil (P < 0.05). There was no significant inhibitory effect in stable silencing of MUC1 expression esophageal cancer nude mice. ConclusionBoth cisplatin and paclitaxel can suppress the growth of MUC1 over-expression esophageal cancer, and cisplatin has greater inhibitory effects than 5-fluorouracil in tumor volume and body weight of nude mice.
Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly associated with warfarin maintenance doses. Warfarin maintenance doses can be accurately predicted by use of dosing algorithms including genetic and clinical information. Although several clinical trials demonstrated mixed results, calling into question the utility of this approach. The present data do not support genetic testing to guide warfarin maintenance doses, but in the setting where genotype data are available, use of this approach is reasonable. Ongoing trials are expected to provide more data, and more work is needed to define dosing algorithms that include appropriate variables in minority populations. All these work will further improve the clinical application of genotype-guided warfarin maintenance doses.
ObjectiveTo evaluate anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease. MethodsWe electronically searched EMbase, PubMed, The Cochrane Library, ClinicalTrials.gov, CNKI, CBM, WanFang Data and VIP databases for cohort studies about the anti-platelet effect of clopidogrel influenced by CYP2C19*17 polymorphism in patients with cardiovascular disease from inception to October 2012. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using the software Rev-Man 5.2. ResultsA total of seven studies involving 12 116 patients were finally included. Three were 5 579 CYP2C19*17 carriers and 6 538 non-carriers. The results of meta-analyses showed that, compared with the CYP2C19*17 non-carriers, lower rate of cardiovascular events (OR=0.85, 95%CI 0.73 to 0.99, P=0.03) and higher bleeding events (OR=1.25, 95%CI 1.05 to 1.50, P=0.01) were found in the CYP2C19*17 carriers. ConclusionCYP2C19*17 carriers is with lower cardiovascular events and higher bleeding events than the CYP2C19*17 non-carriers.
ObjectiveTo analyze genotype frequencies of CYP2C19 in healthy Asian population, and to provide evidence-based data for further personalized drug therapy and pharmacogenomics research. MethodsLiterature was retrieved from digital databases of PubMed, EMbase, The Cochrane Library (Issue 2, 2013), CNKI, WanFang Data, VIP and CBM from their established dates to August, 2013. According to the inclusion and exclusion criteria, the data of the allele frequencies of the gene were extracted, pooled, and analyzed. ResultsA total of 36 articles were included, involving 15 countries and 9 693 healthy populations. Analysis was conducted on regional features, by regions as China, East Asia (China, Korea and Japan), Southeast Asia (Vietnam, Thailand, Malaysia, Singapore, Myanmar and Indonesia), South Asia (India) and West Asia (Palestine, Lebanon, Iran, Turkey and Jordan). The results showed that the genotype frequencies of *1/*1, *1/*2, *1/*3, *2/*2, *2/*3 and *3/*3 were 37.2%, 41.4%, 6.7%, 9.9%, 4.1% and 0.7% (Chinese, n=4 105); 36.4%, 39.1%, 8.8%, 9.5%, 4.9% and 1.3% (East Asian, n=6 198); 44.9%, 41.1%, 4.7%, 7.0%, 1.8% and 0.6% (Southeast Asian, n=1 933); 43.5%, 42.9%, 0.3%, 12.7%, 0.6% and 0.0% (South Asian, n=361); 77.8%, 18.9%, 0.3%, 2.6%, 0.1% and 0.3% (West Asia, n=1 201); and 43.5%, 37.1%, 6.6%, 8.3%, 3.5% and 1.0% (Asian, n=9 693). ConclusionThe present study suggests that there is a great difference on the genotype frequencies of CYP2C19 for different ethnic groups in China, and at different regions in Asia. Besides, genetic variation is impacted by geographical factors such as region and environment.
ObjectiveTo systematically review the diagnostic value of anti-C1q antibodies for lupus nephritis (LN) in Chinese population. MethodsWe electronically searched databases including PubMed, EMbase, CNKI, The Cochrane Library, VIP and WanFang Data for diagnostic accuracy studies of anti-C1q antibodies for LN in Chinese population from inception to 1st March, 2015. Two reviewers independently screened literature, extracted data and assessed the risk bias of included studies by QUADAS tool. Then, meta-analysis was performed by Meta-DiSc 1.4 software and Stata 11.0 software. ResultsA total of 11 studies involving 1 084 systemic lupus erythematosus (SLE) patients were included. Among them, 474 patients were LN. The results of meta-analysis showed that:the pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio of anti-C1q in the diagnosis of LN were 0.67 (95%CI 0.63 to 0.71), 0.69 (95%CI 0.65 to 0.74), 5.09 (95%CI 3.29 to 7.85), 2.18 (95%CI 1.75 to 2.72), and 0.48 (95%CI 0.39 to 0.60), respectively. The area under the curve (AUC) of SROC was 0.749 6 and the Q index value was 0.693 1. The average missed diagnosis rate was 33.0% and the misdiagnosis rate was 31.0%. ConclusionCurrent evidence indicates that anti-C1q antibodies may have some value in the diagnosis of LN. Because of the high missed diagnosis rate and the misdiagnosis rate, it could not be used to diagnose LN alone, and it only could be used as an adjuvant diagnostic indicator for LN. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.