Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therap...Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen“green”natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by downregulating GST expression.Considering the high GST levels in HCC patients,this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.展开更多
BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist ...BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival benefit.This is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight loss.AIM To explore the relationship between BMI and survival in patients with cirrhosis and HCC.METHODS This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers.Patient and tumor characteristics were extracted manually from medical records of each institutions'cancer registries.Patients were stratified according to BMI classes:<25 kg/m^(2)(lean),25-29.9 kg/m^(2)(overweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI classification.We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.RESULTS A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as noncirrhotic.The three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population overall.Within each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),respectively.Underweight patients with a BMI<18.5 kg/m^(2)(n=52)were included in the lean cohort.Of the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were obese.The three BMI classes did not differ by age,MELD,or Child-Pugh class.Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients(71%,62%,49%,P<0.001).Lean patients had significantly larger tumors compared to the other two BMI classes(5.1 vs 4.2 vs 4.2 cm,P<0.001),were more likely outside Milan(56%vs 48%vs 47%,P<0.001),and less likely to undergo transplantation(9%vs 18%vs 18%,P<0.001).While both tumor size(P<0.0001)and elevated alpha fetoprotein(P<0.0001)were associated with worse survival by regression analysis,lean BMI was not(P=0.36).CONCLUSION Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria,reflecting cancer related cachexia from delayed diagnosis.Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit,but not overweight or obese BMI classifications.展开更多
Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their...Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.展开更多
BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience.However,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean...BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience.However,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean populations in Jilin,China,remains inconclusive.AIM To determine the best cut-off of HbA1c for diagnosing DR among the Chinese.METHODS This cross-sectional study included 1933 participants from the Yanbian area of Jilin Province,China.Trained investigators employed a questionnaire-based survey,physical examination,laboratory tests,and fundus photography for the investigation.The best cut-off value for HbA1c was established via the receiver operating characteristic curve.The factors associated with HbA1c-associated risk factors were determined via linear regression.RESULTS The analysis included 887 eligible Chinese Han and Korean participants,591 of whom were assigned randomly to the training set and 296 to the validation set.The prevalence of DR was 3.27% in the total population.HbA1c of 6.2% was the best cut-off value in the training set,while it was 5.9% in the validation set.In both Chinese Han and Korean populations,an HbA1c level of 6.2% was the best cut-off value.The optimal cut-off values of fasting blood glucose(FBG)≥7 mmol/L and<7 mmol/L were 8.1% and 6.2% respectively in Han populations,while those in Korean populations were 6.9%and 5.3%,respectively.Age,body mass index,and FBG were determined as the risk factors impacting HbA1c levels.CONCLUSION HbA1c may serve as a useful diagnostic indicator for DR.An HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82003931,82204766 and 81374062)the Outstanding Youth Foundation of Hunan Provincial Education Department of China(Grant No.:20B445)+3 种基金the Hunan Youth Science and Technology Innovation Talents Project,China(Grant No.:2021RC3100)the Chinese Postdoctoral Science foundation(Grant No.:2021M690974)Changjiang Scholars Program in Ministry Education,People's Republic of China(Program No.:T2019133)the Scientific Research Project of Hunan Provincial Education Department(Project No.:21B0394).
文摘Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen“green”natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by downregulating GST expression.Considering the high GST levels in HCC patients,this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
基金Supported by in part David W Crabb Professorship Endowment at Indiana University School of Medicine and an intramural grant from the Atrium Health Center for Outcomes Research and Evaluation(CORE)(to deLemos AS).
文摘BACKGROUND Obesity is an independent risk factor for the development of hepatocellular carcinoma(HCC)and may influence its outcomes.However,after diagnosis of HCC,like other malignancies,the obesity paradox may exist where higher body mass index(BMI)may in fact confer a survival benefit.This is frequently observed in patients with advanced HCC and cirrhosis,who often present late with advanced tumor features and cancer related weight loss.AIM To explore the relationship between BMI and survival in patients with cirrhosis and HCC.METHODS This is a retrospective cohort study of over 2500 patients diagnosed with HCC between 2009-2019 at two United States academic medical centers.Patient and tumor characteristics were extracted manually from medical records of each institutions'cancer registries.Patients were stratified according to BMI classes:<25 kg/m^(2)(lean),25-29.9 kg/m^(2)(overweight),and>30 kg/m^(2)(obese).Patient and tumor characteristics were compared according to BMI classification.We performed an overall survival analysis using Kaplan Meier by the three BMI classes and after adjusting for Milan criteria.A multivariable Cox regression model was then used to assess known risk factors for survival in patients with cirrhosis and HCC.RESULTS A total of 2548 patients with HCC were included in the analysis of which 11.2%(n=286)were classified as noncirrhotic.The three main BMI categories:Lean(n=754),overweight(n=861),and obese(n=933)represented 29.6%,33.8%,and 36.6%of the total population overall.Within each BMI class,the non-cirrhotic patients accounted for 15%(n=100),12%(n=94),and 11%(n=92),respectively.Underweight patients with a BMI<18.5 kg/m^(2)(n=52)were included in the lean cohort.Of the obese cohort,42%(n=396)had a BMI≥35 kg/m^(2).Out of 2262 patients with cirrhosis and HCC,654(29%)were lean,767(34%)were overweight,and 841(37%)were obese.The three BMI classes did not differ by age,MELD,or Child-Pugh class.Chronic hepatitis C was the dominant etiology in lean compared to the overweight and obese patients(71%,62%,49%,P<0.001).Lean patients had significantly larger tumors compared to the other two BMI classes(5.1 vs 4.2 vs 4.2 cm,P<0.001),were more likely outside Milan(56%vs 48%vs 47%,P<0.001),and less likely to undergo transplantation(9%vs 18%vs 18%,P<0.001).While both tumor size(P<0.0001)and elevated alpha fetoprotein(P<0.0001)were associated with worse survival by regression analysis,lean BMI was not(P=0.36).CONCLUSION Lean patients with cirrhosis and HCC present with larger tumors and are more often outside Milan criteria,reflecting cancer related cachexia from delayed diagnosis.Access to care for hepatitis C virus therapy and liver transplantation confer a survival benefit,but not overweight or obese BMI classifications.
文摘Annual forage legumes are important components of livestock production systems in East Texas and the southeastern US. Forage legumes contribute nitrogen (N) to cropping systems through biological N fixation, and their seasonal biomass production can be managed to complement forage grasses. Our research objectives were to evaluate both warm- and cool-season annual forage legumes as green manure for biomass, N content, ability to enhance soil organic carbon (SOC) and soil N, and impact on post season forage grass crops. Nine warm-season forage legumes (WSL) were spring planted and incorporated as green manure in the fall. Forage rye (Secale cereale L.) was planted following the incorporation of WSL treatments. Eight cool-season forage legumes (CSL) were fall planted in previously fallow plots and incorporated as green manure in late spring. Sorghum-sudangrass (Sorghum bicolor x Sorghum bicolor var. sudanense) was planted over all treatments in early summer after forage rye harvest and incorporation of CSL treatments. Sorghum-sudangrass was harvested in June, August and September, and treatments were evaluated for dry matter and N concentration. Soil cores were taken from each plot, split into depths of 0 to 15, 15 to 30 and 30 to 60 cm, and soil C and N were measured using combustion analysis. Nylon mesh bags containing plant samples were buried at 15 cm and used to evaluate decomposition rate of above ground legume biomass, including change in C and N concentrations. Mungbean (Vigna radiata L. [Wilczek]) had the highest shoot biomass yield (6.24 t DM ha<sup>-1</sup>) and contributed the most total N (167 kg∙ha<sup>-1</sup>) and total C (3043 kg∙ha<sup>-1</sup>) of the WSL tested. Decomposition rate of WSL biomass was rapid in the first 10 weeks and very slow afterward. Winter pea (Pisum sativum L. spp. sativum), arrow leaf clover (Trifolium vesiculosum Savi.), and crimson clover (Trifolium incarnatum L.) were the most productive CSL in this trial. Austrian winter pea produced 8.41 t DM ha<sup>-1</sup> with a total N yield of 319 kg N ha<sup>-1</sup> and total C production of 3835 kg C ha<sup>-1</sup>. The WSL treatments had only small effects on rye forage yield and N concentration, possibly due to mineralization of N from a large SOC pool already in place. The CSL treatments also had only minimal effects on sorghum-sudangrass forage production. Winter pea, arrow leaf and crimson clover were productive cool season legumes and could be useful as green manure crops. Mungbean and cowpea (Vigna unguiculata [L.] Walp.) were highly productive warm season legumes but may include more production risk in green manure systems due to soil moisture competition.
文摘目的分析体质量指数(Body mass index,BMI)与老年慢性心力衰竭(Chronic heart failure,CHF)患者血浆胱抑素C(cystatinC,Cys-C)、N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide,NT-proBNP)水平相关性,并分析血浆Cys-C、NT-proBNP评估老年CHF患者预后价值。方法选择2021年7月—2022年10月在本院接受治疗的192例老年慢性心力衰竭(CHF)患者作为研究对象,按照BMI指数分为肥胖组(49例)、超重组(68例)和正常组(75例)三组。对比各亚组患者血浆Cys-C、NT-proBNP水平差异,采用Pearson相关性分析的方式探究老年CHF患者BMI指数与血浆Cys-C、NT-proBNP相关性,对入组患者实施12个月随访,将患者按照预后情况区分为死亡组和存活组,对比两亚组患者血浆Cys-C、NT-proBNP水平差异并评估预后评估价值。结果肥胖组患者血浆Cys-C、NT-proBNP水平高于超重组,超重组患者血浆Cys-C、NT-proBNP水平高于正常组,差异具有统计学意义(P<0.05);入组老年CHF患者的BMI指数与其血浆Cys-C、NT-proBN水平均呈现明显的正相关性(r=0.7104,P<0.0001)(r=0.6603,P<0.0001);随访12个月显示,死亡组患者的血浆Cys-C、NT-proBNP水平显著高于存活组患者,差异具有统计学意义(P<0.05);血浆Cys-C、NT-proBNP对老年CHF预后评估曲线下面积(area under curv,AUC)为0.6930(P=0.0009)、0.7982(P<0.0001)。结论老年CHF患者随BMI指数升高,血浆Cys-C、NT-proBNP水平逐渐升高,血浆Cys-C、NT-proBNP对老年CHF临床结局具有一定的预测价值,进一步研究有推广应用于老年CHF预后评估潜力。
基金Supported by National Key R&D Program of China,No.2016YFC1305700.
文摘BACKGROUND Glycated hemoglobin A1c(HbA1c)is considered the most suitable for diabetes mellitus diagnosis due to its accuracy and convenience.However,the effect of HbA1c on diabetic retinopathy(DR)in the Han and Korean populations in Jilin,China,remains inconclusive.AIM To determine the best cut-off of HbA1c for diagnosing DR among the Chinese.METHODS This cross-sectional study included 1933 participants from the Yanbian area of Jilin Province,China.Trained investigators employed a questionnaire-based survey,physical examination,laboratory tests,and fundus photography for the investigation.The best cut-off value for HbA1c was established via the receiver operating characteristic curve.The factors associated with HbA1c-associated risk factors were determined via linear regression.RESULTS The analysis included 887 eligible Chinese Han and Korean participants,591 of whom were assigned randomly to the training set and 296 to the validation set.The prevalence of DR was 3.27% in the total population.HbA1c of 6.2% was the best cut-off value in the training set,while it was 5.9% in the validation set.In both Chinese Han and Korean populations,an HbA1c level of 6.2% was the best cut-off value.The optimal cut-off values of fasting blood glucose(FBG)≥7 mmol/L and<7 mmol/L were 8.1% and 6.2% respectively in Han populations,while those in Korean populations were 6.9%and 5.3%,respectively.Age,body mass index,and FBG were determined as the risk factors impacting HbA1c levels.CONCLUSION HbA1c may serve as a useful diagnostic indicator for DR.An HbA1c level of 6.2% may be an appropriate cut-off value for DR detection in the Chinese population.
