Due to the difference in density between the discharge effluent and coastal water,partially treated wastewater is often discharged into the marine environment as a buoyant jet via submarine outfalls with multiport dif...Due to the difference in density between the discharge effluent and coastal water,partially treated wastewater is often discharged into the marine environment as a buoyant jet via submarine outfalls with multiport diffusers.The dilution characteristics of effluent discharge(dual buoyant jets)in a wavy cross-flow environment were studied in a laboratory.The planar laser-induced fluorescence technique was used to obtain the concentration data of the jets.The effects of different environmental variables on the diffusion and dilution characteristics of the jets were examined through physical experiments,dimensional analysis,and empirical formulations.It was found that the dilution process of the dual jets could be divided into two components:the original jet component and the effluent cloud component.The jet-to-current velocity ratio was the main parameter affecting the concentration levels of the effluent cloud.The merging of the two jets increased the jet concentration in the flow field.When the jets traveled further downstream,the axial dilution increased gradually and then increased significantly along the axis.Under the effects of strong waves,the concentration contours branched into two peaks,and the mean dilution became more significant than under the effects of weak waves.Therefore,the dilution of the effluent discharge was expected to be significant under strong wave effects because the hydrodynamic force increased.A dilution equation was derived to improve our understanding of the dilution process of buoyant jets in a wavy cross-flow environment.This equation was used to determine the influences of the jet-to-current velocity ratio,wave-to-current velocity ratio,and Strouhal number on the minimum jet dilution.It revealed that the wave and buoyancy effects in effluent discharges were significant.展开更多
BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of h...BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.展开更多
Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed...Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.展开更多
This paper presents a study on the improvement of wind field hindcasts for two typical tropical cyclones, i.e., Fanapi and Meranti, which occurred in 2010. The performance of the three existing models for the hindcast...This paper presents a study on the improvement of wind field hindcasts for two typical tropical cyclones, i.e., Fanapi and Meranti, which occurred in 2010. The performance of the three existing models for the hindcasting of cyclone wind fields is first examined, and then two modification methods are proposed to improve the hindcasted results. The first one is the superposition method, which superposes the wind field calculated from the parametric cyclone model on that obtained from the cross-calibrated multi-platform (CCMP) reanalysis data. The radius used for the superposition is based on an analysis of the minimum difference between the two wind fields. The other one is the direct modification method, which directly modifies the CCMP reanalysis data according to the ratio of the measured maximum wind speed to the reanalyzed value as well as the distance from the cyclone center. Using these two methods, the problem of underestimation of strong winds in reanalysis data can be overcome. Both methods show considerable improvements in the hindcasting of tropical cyclone wind fields, compared with the cyclone wind model and the reanalysis data.展开更多
China’s continuous and rapid economic growth has led to the reclamation of large sections of the intertidal mud coast in combination with port construction,such as that of the proposed Tongzhou Bay port on the Jiangs...China’s continuous and rapid economic growth has led to the reclamation of large sections of the intertidal mud coast in combination with port construction,such as that of the proposed Tongzhou Bay port on the Jiangsu coast.These reclamations threaten the local ecosystem services.An ecotope distribution map was created and a hydrodynamic numerical model of Tongzhou Bay was set up to quantify the impacts of reclamation on the ecosystem.Based on the field data and model results,several abiotic features were classified into 11 ecotopes and visualized in an ecotope map of the Tongzhou Bay ecosystem.Validation with spatial distributions of two threatened shorebird species(bar-tailed godwit and great knot) showed confirmation with the mid-range and low-range littoral zones(inundated from 40% to 100% of a tidal cycle),indicating the importance of the areas with these conditions to these populations.Overlaying the ecotope map with recent and proposed land reclamation schemes revealed a loss of ecotopes,composed of the high-range(42%),mid-range(48%),and low-range(38%) littoral habitats,corresponding to a 44%-45% loss of the most important ecotopes for bar-tailed godwit and great knot(mid-range and low-range littoral zones).These results confirm the applicability of the novel ecotope assessment approach in practice.展开更多
The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotro...The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis(ALS).To correlate NLR with disease progression and survival in sporadic ALS,1030 patients with ALS between January 2012 and December 2018 were included in this study.These patients were assigned into three groups according to their NLR values:Group 1(NLR<2,n=544[52.8%]),Group 2(NLR=2–3,n=314[30.5%]),and Group 3(NLR>3,n=172[16.7%]).All patients were followed up until April 2020.Patients in Group 3 had a significantly older onset age,a lower score on the Revised ALS Functional Rating Scale,and rapidly progressing disease conditions.Furthermore,faster disease progression rates were associated with higher NLR values(odds ratio=1.211,95%confidence interval[CI]:1.090–1.346,P<0.001)after adjusting for other risk factors.Compared with Groups 1 and 2,the survival time in Group 3 was significantly shorter(log-rank P=0.002).The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters(hazard ratio[HR]=1.079,95%CI:1.016–1.146,P=0.014).The effects on ALS survival remained significant when adjusted for treatment(HR=1.074,95%CI:1.012–1.141,P_(trend)=0.019)or when considering the stratified NLR value(HR=1.115,95%CI:1.009–1.232,P_(trend)=0.033).Thus,the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS.The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University,China(approval No.2015(236))on December 23,2015.展开更多
Objective:Gliomas are the most common tumors in the central nervous system.The cancer susceptibility candidate 15(CASC15)gene has been reported to be a susceptibility gene for several types of cancer.No studies have b...Objective:Gliomas are the most common tumors in the central nervous system.The cancer susceptibility candidate 15(CASC15)gene has been reported to be a susceptibility gene for several types of cancer.No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms(SNPs)on glioma risk.Methods:In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility,the first association study in a relatively large sample,which consisted of 171 patients and 228 healthy controls recruited from China,was performed.The contribution of SNPs(rs6939340 A>G,rs4712653 T>C and rs9295536 C>A)to the risk of glioma was evaluated by multinomial logistic regression,based on the calculation of the odds ratio(OR)and 95%confidence interval(CI).Results:In the single locus and combined analysis,it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk.However,in the stratified analysis,a significant decrease in risk of glioma was observed in subjects of<60 months old with the rs4712653 TT genotype,when compared to those with the CC/CT genotype(OR=0.12,95%CI=0.02-0.91,P=0.041).Conclusion:The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children.However,more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.展开更多
Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other f...Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other factors also may alter the glioma risk,among which gene polymorphisms may play prominent role in glioma susceptibility.Base excision repair(BER)is a DNA repair mechanism that maintains genome integrity and guarantees DNA base modification properly.Many signifcant and common proteins involved in the BER pathway are associated with cancer.展开更多
Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).Howev...Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.展开更多
Main text The levodopa-induced dyskinesias(LIDs)in Parkinson’disease(PD)patients during levodopa treatment can lead to significant disability.Accumulative evidence has suggested that the younger the age of onset,the ...Main text The levodopa-induced dyskinesias(LIDs)in Parkinson’disease(PD)patients during levodopa treatment can lead to significant disability.Accumulative evidence has suggested that the younger the age of onset,the more likely the development of LIDs[1].Till now,most of the studies on clinical or genetic risk factors for LIDs were cross-sectional[2],or included limited sample size[3],or mainly included late-onset PD patients[4].Here,we investigated the incidence of LIDs in the early stage of early-onset PD(EOPD),including the first 5 years of duration and the first 5 years of dopamine replacement therapy(DRT),and established and validated clinicalgenetic models for LID prediction.Detailed methods are provided in Supplementary File 1.展开更多
基金supported by the Fundamental Research Funds for the Central Universities of China(Grant No.B200202057)and the National Natural Science Foundation of China(Grant No.51979076)。
文摘Due to the difference in density between the discharge effluent and coastal water,partially treated wastewater is often discharged into the marine environment as a buoyant jet via submarine outfalls with multiport diffusers.The dilution characteristics of effluent discharge(dual buoyant jets)in a wavy cross-flow environment were studied in a laboratory.The planar laser-induced fluorescence technique was used to obtain the concentration data of the jets.The effects of different environmental variables on the diffusion and dilution characteristics of the jets were examined through physical experiments,dimensional analysis,and empirical formulations.It was found that the dilution process of the dual jets could be divided into two components:the original jet component and the effluent cloud component.The jet-to-current velocity ratio was the main parameter affecting the concentration levels of the effluent cloud.The merging of the two jets increased the jet concentration in the flow field.When the jets traveled further downstream,the axial dilution increased gradually and then increased significantly along the axis.Under the effects of strong waves,the concentration contours branched into two peaks,and the mean dilution became more significant than under the effects of weak waves.Therefore,the dilution of the effluent discharge was expected to be significant under strong wave effects because the hydrodynamic force increased.A dilution equation was derived to improve our understanding of the dilution process of buoyant jets in a wavy cross-flow environment.This equation was used to determine the influences of the jet-to-current velocity ratio,wave-to-current velocity ratio,and Strouhal number on the minimum jet dilution.It revealed that the wave and buoyancy effects in effluent discharges were significant.
基金Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme,No.2013ZX10005002Beijing the Special Clinical Application Research and Translational Grants,No.Z151100004015221
文摘BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.
基金supported by grants from the National Major Special Project for the Prevention and Treatment of Major Infectious Diseases:AIDS and viral hepatitis(2013ZX10005002,2018ZX10725506)the National Key Research and Development Program(2017YFC0908903)。
文摘Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
基金supported by the National Natural Science Foundation of China(Grants No.51309092 and 51379072)the Special Fund for Public Welfare Industry of the Ministry of Water Resources of China(Grant No.201201045)+1 种基金the Natural Science Fund for Colleges and Universities in Jiangsu Province(Grant No.BK20130833)the Fundamental Research Funds for the Central Universities(Grants No.2015B16014 and 2013B03414)
文摘This paper presents a study on the improvement of wind field hindcasts for two typical tropical cyclones, i.e., Fanapi and Meranti, which occurred in 2010. The performance of the three existing models for the hindcasting of cyclone wind fields is first examined, and then two modification methods are proposed to improve the hindcasted results. The first one is the superposition method, which superposes the wind field calculated from the parametric cyclone model on that obtained from the cross-calibrated multi-platform (CCMP) reanalysis data. The radius used for the superposition is based on an analysis of the minimum difference between the two wind fields. The other one is the direct modification method, which directly modifies the CCMP reanalysis data according to the ratio of the measured maximum wind speed to the reanalyzed value as well as the distance from the cyclone center. Using these two methods, the problem of underestimation of strong winds in reanalysis data can be overcome. Both methods show considerable improvements in the hindcasting of tropical cyclone wind fields, compared with the cyclone wind model and the reanalysis data.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFC0405401)the Science and Technology Project of Traffic and Transportation in Jiangsu Province(Grant No.2017ZX01).
文摘China’s continuous and rapid economic growth has led to the reclamation of large sections of the intertidal mud coast in combination with port construction,such as that of the proposed Tongzhou Bay port on the Jiangsu coast.These reclamations threaten the local ecosystem services.An ecotope distribution map was created and a hydrodynamic numerical model of Tongzhou Bay was set up to quantify the impacts of reclamation on the ecosystem.Based on the field data and model results,several abiotic features were classified into 11 ecotopes and visualized in an ecotope map of the Tongzhou Bay ecosystem.Validation with spatial distributions of two threatened shorebird species(bar-tailed godwit and great knot) showed confirmation with the mid-range and low-range littoral zones(inundated from 40% to 100% of a tidal cycle),indicating the importance of the areas with these conditions to these populations.Overlaying the ecotope map with recent and proposed land reclamation schemes revealed a loss of ecotopes,composed of the high-range(42%),mid-range(48%),and low-range(38%) littoral habitats,corresponding to a 44%-45% loss of the most important ecotopes for bar-tailed godwit and great knot(mid-range and low-range littoral zones).These results confirm the applicability of the novel ecotope assessment approach in practice.
基金supported by the Science and Technology Bureau Fund of Sichuan Province of China,No.2020YFS0220the China Postdoctoral Science Foundation,No.2019M653427+1 种基金Postdoctoral Research Project,West China Hospital,Sichuan University of China,No.2019HXBH029Health Commission of Sichuan Province of China,No.20PJ038(all to QQW)。
文摘The neutrophil-to-lymphocyte ratio(NLR)is considered a robust prognostic biomarker for predicting patient survival outcomes in many diseases.However,it remains unclear whether it can be used as a biomarker for amyotrophic lateral sclerosis(ALS).To correlate NLR with disease progression and survival in sporadic ALS,1030 patients with ALS between January 2012 and December 2018 were included in this study.These patients were assigned into three groups according to their NLR values:Group 1(NLR<2,n=544[52.8%]),Group 2(NLR=2–3,n=314[30.5%]),and Group 3(NLR>3,n=172[16.7%]).All patients were followed up until April 2020.Patients in Group 3 had a significantly older onset age,a lower score on the Revised ALS Functional Rating Scale,and rapidly progressing disease conditions.Furthermore,faster disease progression rates were associated with higher NLR values(odds ratio=1.211,95%confidence interval[CI]:1.090–1.346,P<0.001)after adjusting for other risk factors.Compared with Groups 1 and 2,the survival time in Group 3 was significantly shorter(log-rank P=0.002).The NLR value was considered an independent parameter for the prediction of survival in ALS patients after normalizing for all other potential parameters(hazard ratio[HR]=1.079,95%CI:1.016–1.146,P=0.014).The effects on ALS survival remained significant when adjusted for treatment(HR=1.074,95%CI:1.012–1.141,P_(trend)=0.019)or when considering the stratified NLR value(HR=1.115,95%CI:1.009–1.232,P_(trend)=0.033).Thus,the NLR may help to predict the rate of disease progression and survival in patients with sporadic ALS.The study was approved by the Institutional Ethics Committee of West China Hospital of Sichuan University,China(approval No.2015(236))on December 23,2015.
基金funded by grants from the Natural Science FoundationofGuangdongProvince(No.2020A1515010188)the National Natural Science Foundation of China(Nos.81802346 and 81672496)the Science and Technology Project of Guangzhou(No.201804010042).
文摘Objective:Gliomas are the most common tumors in the central nervous system.The cancer susceptibility candidate 15(CASC15)gene has been reported to be a susceptibility gene for several types of cancer.No studies have been carried out on the predisposing effect of CASC15 gene single nucleotide polymorphisms(SNPs)on glioma risk.Methods:In order to determine whether CASC15 gene SNPs are involved in glioma susceptibility,the first association study in a relatively large sample,which consisted of 171 patients and 228 healthy controls recruited from China,was performed.The contribution of SNPs(rs6939340 A>G,rs4712653 T>C and rs9295536 C>A)to the risk of glioma was evaluated by multinomial logistic regression,based on the calculation of the odds ratio(OR)and 95%confidence interval(CI).Results:In the single locus and combined analysis,it was revealed that the genetic risk score had no significant associations between CASC15 gene SNPs and glioma risk.However,in the stratified analysis,a significant decrease in risk of glioma was observed in subjects of<60 months old with the rs4712653 TT genotype,when compared to those with the CC/CT genotype(OR=0.12,95%CI=0.02-0.91,P=0.041).Conclusion:The present study provides referential evidence on the association between the genetic predisposition of the CASC15 gene and glioma risk in Chinese children.However,more well-designed case-control studies and functional experiments are needed to further explore the role of CASC15 gene SNPs.
基金supported by grants from the National Natural Science Foundation of China(81802346)the Discipline Promotion Project of the First Affiliated Hospital of Air Force Medical University(XJZT18MJ49).
文摘Glioma is an aggressive malignant primary tumor in the central nervous system[1,2].Although the pathogenesis of glioma is unclear,the only identified environmental risk fac-tor is ionizing radiation[3].However,other factors also may alter the glioma risk,among which gene polymorphisms may play prominent role in glioma susceptibility.Base excision repair(BER)is a DNA repair mechanism that maintains genome integrity and guarantees DNA base modification properly.Many signifcant and common proteins involved in the BER pathway are associated with cancer.
基金supported by grants from the National Natural Science Foundation of China(82070588)the High Level Creative Talents from Department of Public Health in Zhejiang Proince(S2032102600032)+2 种基金Project of New Century 551 Talent Nurturing in WenzhouGT was supported in part by grants from the School of Medicine,University of Verona,Verona,ItalyCDB was supported in part by the Southampton NIHR Biomedical Research Centre(IS-BRC-20004),UK.
文摘Background and Aims:Previous studies have reported that the single nucleotide polymorphisms(SNPs)of SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease(NAFLD).However,no studies have examined the effect of interactions between these three genotypes to affect liver disease severity.We assessed the effect of these three SNPs on nonalcoholic steatohepatitis(NASH)and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD.Methods:We enrolled 415 consecutive adult individuals with biopsy-proven NAFLD.Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491,PARVB-rs5764455 and PNPLA3-rs738409.Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction(GMDR)analysis.Results:The mean±standard deviation age of these 415 patients was 41.3±12.5 years,and 75.9%were men.Patients with SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH,even after adjustment for age,sex and body mass index.GMDR analysis showed that the combination of all three SNPs was the best model for predicting NASH.Additionally,the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C.Conclusions:NAFLD patients carrying the SAMM50-rs738491 TT,PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH.These three SNPs may synergistically interact to increase susceptibility to NASH.
基金This study was supported by the National Key Research and Development Program of China(2018YFC1312001 and 2016YFC0901504)the National Natural Science Foundation of China(81971188)the 1.3.5 project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYJC18038,ZYJC18003 and 2019HXFH046).
文摘Main text The levodopa-induced dyskinesias(LIDs)in Parkinson’disease(PD)patients during levodopa treatment can lead to significant disability.Accumulative evidence has suggested that the younger the age of onset,the more likely the development of LIDs[1].Till now,most of the studies on clinical or genetic risk factors for LIDs were cross-sectional[2],or included limited sample size[3],or mainly included late-onset PD patients[4].Here,we investigated the incidence of LIDs in the early stage of early-onset PD(EOPD),including the first 5 years of duration and the first 5 years of dopamine replacement therapy(DRT),and established and validated clinicalgenetic models for LID prediction.Detailed methods are provided in Supplementary File 1.