AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent l...AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.展开更多
The knowledge on the ionic structure of YCl_(3)-KCl molten system is of guiding significance for the practical production of yttrium metals and yttrium alloys via molten salt electrolysis using this system as electrol...The knowledge on the ionic structure of YCl_(3)-KCl molten system is of guiding significance for the practical production of yttrium metals and yttrium alloys via molten salt electrolysis using this system as electrolyte.In this paper,the theoretical Raman spectra of the ionic groups which may exist in YCl_(3)-KCl molten system are simulated by quantum chemical calculation using Gaussian09 and Gauss View 5.0 programs based on density functional theory(DFT).Then the ionic structures of 20 mol%-60 mol%YCl_(3)-KCl molten salt systems are studied by comparing the Raman shift values of the bands in the theoretical Raman spectra of different ionic groups with the experimental spectra of this system.YCl_(6)^(3-),Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)are thought to exist in the molten system.With the increase of temperature,the relative content of YCl_(6)^(3-)ionic groups increases while those of Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)ionic groups decrease.Moreover,the"lifetime"of all ionic groups decreases within the temperature range of 692-730℃.Meanwhile,the relative contents of Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)increase with the increase of YCl_(3)content,while that of YCl_(6)^(3-)decreases.The wave function analysis of the four ionic groups(YCl_(6)^(3-),Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-),and Y_(2)Cl_(9)^(3-))is carried out by Multiwfn program.The net charge in each group,the direction of electron migration during the formation of each group,the sites where electrophilic and nucleophilic reactions are most likely to occur in each ionic group,and the order of bond breaking during chemical reactions for the four groups are obtained.展开更多
Background：Orthotopic liver transplantation （OLT） improves the prognosis of patients with hepatocellular carcinoma （HCC）.Moreover,the complement system is a powerful immune effector that can affect liver function...Background：Orthotopic liver transplantation （OLT） improves the prognosis of patients with hepatocellular carcinoma （HCC）.Moreover,the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis.However,studies correlating the complement system with tacrolimus metabolism after OLT are scarce.In this study,the role of single nucleotide polymorphisms （SNPs） associated with the sixth complement component （C6） in tacrolimus metabolism was investigated during the early stages of liver transplantation.Methods：The study enrolled 135 adult patients treated with OLT for HCC between August 2011 and October 2013.Ten SNPs in C6 gene and rs776746 in cytochrome P450 3A5 （CYP3A5） gene were investigated.The tacrolilnus levels were monitored daily during 4 weeks after transplantation.Results：Both donor and recipient CYP3A5 rs776746 allele A were correlated with decreased concentration/dose （C/D） ratios.Recipient C6 rs9200 allele G and donor C6 rs10052999 homozygotes were correlated with lower C/D ratios.Recipient CYP3A5 rs776746 allele A （yielded median tacrolimus C/D ratios of 225.90 at week 1 and 123.61 at week 2）,C6 rs9200 allele G （exhibited median tacrolimus C/D ratios of 211.31 at week l,110.23 at week 2,and 99.88 at week 3）,and donor CYP3A5 rs776746 allele A （exhibited median C/D ratios of 210.82 at week l,111.06 at week 2,77.49 at week 3,and 85.60 at week 4） and C6 rs 10052999 homozygote （exhibited median C/D ratios of 167.59 at week 2,157.99 at week 3,and 155.36 at week 4） were associated with rapid tacrolimus metabolism.With increasing number of these alleles,patients were found to have lower tacrolimus C/D ratios at various time points during the 4 weeks after transplantation.In multiple linear regression analysis,recipient C6 rs9200 group （AA vs.GG/GA） was found to be related to tacrolimus metabolism at weeks 1,2,and 3 （P =0.005,P =0.045,and P =0.033,respectively）,whereas donor C6 rs10052999 group （CC/TT vs.TC） was demonstrated to be correlated with tacrolimus metabolism only at week 4 （P =0.001）.Conclusions：Recipient C6 gene rs9200 polymorphism and donor C6 gene rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in patients with HCC after OLT.展开更多
基金Projects(N182503033N172502003)supported by the Fundamental Research Funds for the Central Universities,China+1 种基金Project(2018M640258)supported by Postdoctoral Research Foundation of ChinaProject(GUIKE AA18118030)supported by Guangxi Innovation-driven Development Program,China。
基金The National Natural Science Foundation of China, No. 30080016 and No. 30470977
文摘AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4q through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients. METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR). PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. Comparison between LOH frequency and clinicopathological factors were performed by χ2 test. RESULTS: Data were collected on all informative loci. The average LOH frequency on 4q was 28.56%. The D4S2915 locus showed highest LOH frequency (36.17%). Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1), another flanked by D4S407 and D4S2939 locus (4q25-31.1). None case showed complete deletion of 4q, most cases displayed interstitial deletion pattern solely. Furthermore, compared with clinicopathological features, a significant relationship was observed between LOH frequencies on D4S3018locus. In tumors larger than 5 cm in diameter, LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%, P = 0.01). On D4S1534 locus, LOH was significantly associated with liver metastasis (80% vs 17.25%, P = 0.012). No relationship was detected on other locus compared with clinicopathologial features. CONCLUSION: By high resolution deletion mapping, two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected, which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.
基金financially supported by the National Natural Science Foundation of China (No.51974081)the Fundamental Research Funds for the Central Universities (No.N2225045)MOE of China and WEIQIAO Industry-Education Cooperation Project (No.2021021800102)。
文摘The knowledge on the ionic structure of YCl_(3)-KCl molten system is of guiding significance for the practical production of yttrium metals and yttrium alloys via molten salt electrolysis using this system as electrolyte.In this paper,the theoretical Raman spectra of the ionic groups which may exist in YCl_(3)-KCl molten system are simulated by quantum chemical calculation using Gaussian09 and Gauss View 5.0 programs based on density functional theory(DFT).Then the ionic structures of 20 mol%-60 mol%YCl_(3)-KCl molten salt systems are studied by comparing the Raman shift values of the bands in the theoretical Raman spectra of different ionic groups with the experimental spectra of this system.YCl_(6)^(3-),Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)are thought to exist in the molten system.With the increase of temperature,the relative content of YCl_(6)^(3-)ionic groups increases while those of Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)ionic groups decrease.Moreover,the"lifetime"of all ionic groups decreases within the temperature range of 692-730℃.Meanwhile,the relative contents of Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-)and Y_(2)Cl_(9)^(3-)increase with the increase of YCl_(3)content,while that of YCl_(6)^(3-)decreases.The wave function analysis of the four ionic groups(YCl_(6)^(3-),Y_(2)Cl_(7)^(-),Y_(2)Cl_(8)^(2-),and Y_(2)Cl_(9)^(3-))is carried out by Multiwfn program.The net charge in each group,the direction of electron migration during the formation of each group,the sites where electrophilic and nucleophilic reactions are most likely to occur in each ionic group,and the order of bond breaking during chemical reactions for the four groups are obtained.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81370579） and the Science and Technology Commission of Shanghai Municipality, China （No. 134119a6300）.
文摘Background：Orthotopic liver transplantation （OLT） improves the prognosis of patients with hepatocellular carcinoma （HCC）.Moreover,the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis.However,studies correlating the complement system with tacrolimus metabolism after OLT are scarce.In this study,the role of single nucleotide polymorphisms （SNPs） associated with the sixth complement component （C6） in tacrolimus metabolism was investigated during the early stages of liver transplantation.Methods：The study enrolled 135 adult patients treated with OLT for HCC between August 2011 and October 2013.Ten SNPs in C6 gene and rs776746 in cytochrome P450 3A5 （CYP3A5） gene were investigated.The tacrolilnus levels were monitored daily during 4 weeks after transplantation.Results：Both donor and recipient CYP3A5 rs776746 allele A were correlated with decreased concentration/dose （C/D） ratios.Recipient C6 rs9200 allele G and donor C6 rs10052999 homozygotes were correlated with lower C/D ratios.Recipient CYP3A5 rs776746 allele A （yielded median tacrolimus C/D ratios of 225.90 at week 1 and 123.61 at week 2）,C6 rs9200 allele G （exhibited median tacrolimus C/D ratios of 211.31 at week l,110.23 at week 2,and 99.88 at week 3）,and donor CYP3A5 rs776746 allele A （exhibited median C/D ratios of 210.82 at week l,111.06 at week 2,77.49 at week 3,and 85.60 at week 4） and C6 rs 10052999 homozygote （exhibited median C/D ratios of 167.59 at week 2,157.99 at week 3,and 155.36 at week 4） were associated with rapid tacrolimus metabolism.With increasing number of these alleles,patients were found to have lower tacrolimus C/D ratios at various time points during the 4 weeks after transplantation.In multiple linear regression analysis,recipient C6 rs9200 group （AA vs.GG/GA） was found to be related to tacrolimus metabolism at weeks 1,2,and 3 （P =0.005,P =0.045,and P =0.033,respectively）,whereas donor C6 rs10052999 group （CC/TT vs.TC） was demonstrated to be correlated with tacrolimus metabolism only at week 4 （P =0.001）.Conclusions：Recipient C6 gene rs9200 polymorphism and donor C6 gene rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in patients with HCC after OLT.
