Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic predict...Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction tool.Besides,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it.It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these patients.The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological features.Methods:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical resection.We randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS.By analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive models.Results:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in imaging.RFS nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and Nomograms in Hepatectomy Patients with Hepatitis B VirusRelated Hepatocellular Carcinoma,indicating better discrimination capability.According to the models,we fitted the linear prediction equations.These results were validated in the validation cohort.Conclusions:Compared with previous radiography model,the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC.Our models may preoperatively identify patients with high risk of recurrence.These patients may benefit from neoadjuvant therapy which may improve the patients’outcomes.展开更多
The failure analysis was conducted on unqualified torsion bar spring in automobile suspension system used for light vehicles during engine test.The effects of through hardening,surface induction hardening,quenching an...The failure analysis was conducted on unqualified torsion bar spring in automobile suspension system used for light vehicles during engine test.The effects of through hardening,surface induction hardening,quenching and tempering,and tempering temperature on the microstructure and fatigue life of 45CrNiMoVA steel torsion bars were also investigated.Results showed that only the torsion bar spring after through quenching and tempering is subjected to surface induction quenching and tempering to achieve the fatigue life of the qualified torsion bar.The fatigue life of torsion bar spring reaches 3×10^(5) cycles more than the required 2×10^(5) cycles.This is because the distribution of gradient microstructure was helpful to relieve the applied stress during the fatigue process.The microstructure of the non-hardened region,which consists of tempered sorbite regardless of whether it is tempered at 330 or 430℃,contributes to minimizing the impact of temper brittleness on the fatigue life of the torsion bar.Consequently,the fatigue life of the torsion bar is relatively unaffected by temper brittleness due to the presence of tempered sorbite in its non-hardened regions.And the reason for the unqualified fatigue life was that the depth and hardness of the hardened region did not meet the standard requirements of 5–7 mm and 47–52 HRC,respectively.展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
Background and Aims:To validate prognostic performance of the China liver cancer(CNLC)staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer(BCLC)staging system for Chine...Background and Aims:To validate prognostic performance of the China liver cancer(CNLC)staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer(BCLC)staging system for Chinese hepatocellular carcinoma(HCC)treated with transarterial chemoembolization(TACE).Methods:This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals.Based on overall survival(OS),the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination[C statistic and Akaike information criterion(AIC)],monotonicity of the gradient(linear trend chi-square test),homogeneity(likelihood ratio chisquare test),and calibration(calibration plots).A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes.Results:Median OS was 19.1(18.2–20.0)months,with significant differences in OS between stages defined by the CNLC and BCLC observed(p<0.001).The CNLC performed better than the BCLC regarding model discrimination(C-index:0.661 vs.0.644;AIC:10,583.28 vs.10,583.72),model monotonicity of the gradient(linear trend chi-square test:66.107 vs.57.418;p<0.001),model homogeneity(159.2 vs.158.7;p<0.001).Both staging systems had good model calibration.Similar results were observed in the prospective cohort.Conclusions:Combining model discrimination,gradient monotonicity,homogeneity,and calibration,the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.展开更多
Hepatitis B virus(HBV)infection is still a severe health problem in the world,and chronic hepatitis B(CHB)is the major cause of serious HBV-related complications,including fibrosis,hepatic failure,and hepatocellular c...Hepatitis B virus(HBV)infection is still a severe health problem in the world,and chronic hepatitis B(CHB)is the major cause of serious HBV-related complications,including fibrosis,hepatic failure,and hepatocellular carcinoma.It is difficult for CHB patients to achieve complete cure as the currently available antiviral drugs can hardly eradicate covalently closed circular DNA(cccDNA)in the infected liver.Since detecting intrahepatic cccDNA needs invasive procedure,it is urgent to find a noninvasive indicator to reflect the activity of cccDNA.Recently,growing numbers of studies have indicated that serum HBV RNA could be regarded as a new biomarker for CHB activity.In order to illustrate the molecular biology and clinical characteristics of HBV RNA,we systematically reviewed the latest research to summarize the role of HBV RNA in HBV replication and pathogenicity,and to better estimate its potential function as a remarkable biomarker in clinical application.Meanwhile,we will also point out the deficiencies of current research,and discuss the future direction of HBV RNA study.展开更多
基金supported by grants from the Shanghai Rising-Star Program(19QA1408700)the National Natural Science Founda-tion of China(81972575 and 81521091)Clinical Research Plan of SHDC(SHDC2020CR5007)。
文摘Background:Early singular nodular hepatocellular carcinoma(HCC)is an ideal surgical indication in clinical practice.However,almost half of the patients have tumor recurrence,and there is no reliable prognostic prediction tool.Besides,it is unclear whether preoperative neoadjuvant therapy is necessary for patients with early singular nodular HCC and which patient needs it.It is critical to identify the patients with high risk of recurrence and to treat these patients preoperatively with neoadjuvant therapy and thus,to improve the outcomes of these patients.The present study aimed to develop two prognostic models to preoperatively predict the recurrence-free survival(RFS)and overall survival(OS)in patients with singular nodular HCC by integrating the clinical data and radiological features.Methods:We retrospective recruited 211 patients with singular nodular HCC from December 2009 to January 2019 at Eastern Hepatobiliary Surgery Hospital(EHBH).They all met the surgical indications and underwent radical resection.We randomly divided the patients into the training cohort(n=132)and the validation cohort(n=79).We established and validated multivariate Cox proportional hazard models by the preoperative clinicopathologic factors and radiological features for association with RFS and OS.By analyzing the receiver operating characteristic(ROC)curve,the discrimination accuracy of the models was compared with that of the traditional predictive models.Results:Our RFS model was based on HBV-DNA score,cirrhosis,tumor diameter and tumor capsule in imaging.RFS nomogram had fine calibration and discrimination capabilities,with a C-index of 0.74(95%CI:0.68-0.80).The OS nomogram,based on cirrhosis,tumor diameter and tumor capsule in imaging,had fine calibration and discrimination capabilities,with a C-index of 0.81(95%CI:0.74-0.87).The area under the receiver operating characteristic curve(AUC)of our model was larger than that of traditional liver cancer staging system,Korea model and Nomograms in Hepatectomy Patients with Hepatitis B VirusRelated Hepatocellular Carcinoma,indicating better discrimination capability.According to the models,we fitted the linear prediction equations.These results were validated in the validation cohort.Conclusions:Compared with previous radiography model,the new-developed predictive model was concise and applicable to predict the postoperative survival of patients with singular nodular HCC.Our models may preoperatively identify patients with high risk of recurrence.These patients may benefit from neoadjuvant therapy which may improve the patients’outcomes.
基金support from the National Natural Science Foundation of China(No.52174351).
文摘The failure analysis was conducted on unqualified torsion bar spring in automobile suspension system used for light vehicles during engine test.The effects of through hardening,surface induction hardening,quenching and tempering,and tempering temperature on the microstructure and fatigue life of 45CrNiMoVA steel torsion bars were also investigated.Results showed that only the torsion bar spring after through quenching and tempering is subjected to surface induction quenching and tempering to achieve the fatigue life of the qualified torsion bar.The fatigue life of torsion bar spring reaches 3×10^(5) cycles more than the required 2×10^(5) cycles.This is because the distribution of gradient microstructure was helpful to relieve the applied stress during the fatigue process.The microstructure of the non-hardened region,which consists of tempered sorbite regardless of whether it is tempered at 330 or 430℃,contributes to minimizing the impact of temper brittleness on the fatigue life of the torsion bar.Consequently,the fatigue life of the torsion bar is relatively unaffected by temper brittleness due to the presence of tempered sorbite in its non-hardened regions.And the reason for the unqualified fatigue life was that the depth and hardness of the hardened region did not meet the standard requirements of 5–7 mm and 47–52 HRC,respectively.
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
文摘Background and Aims:To validate prognostic performance of the China liver cancer(CNLC)staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer(BCLC)staging system for Chinese hepatocellular carcinoma(HCC)treated with transarterial chemoembolization(TACE).Methods:This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals.Based on overall survival(OS),the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination[C statistic and Akaike information criterion(AIC)],monotonicity of the gradient(linear trend chi-square test),homogeneity(likelihood ratio chisquare test),and calibration(calibration plots).A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes.Results:Median OS was 19.1(18.2–20.0)months,with significant differences in OS between stages defined by the CNLC and BCLC observed(p<0.001).The CNLC performed better than the BCLC regarding model discrimination(C-index:0.661 vs.0.644;AIC:10,583.28 vs.10,583.72),model monotonicity of the gradient(linear trend chi-square test:66.107 vs.57.418;p<0.001),model homogeneity(159.2 vs.158.7;p<0.001).Both staging systems had good model calibration.Similar results were observed in the prospective cohort.Conclusions:Combining model discrimination,gradient monotonicity,homogeneity,and calibration,the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.
基金This work was supported by National Key Basic Research Program of China(2014CB542102)National Key Research and Development Program of China(2016YFC1302303)+3 种基金National Human Genetic Resources Sharing Service Platform(2005DKA21300)Science Fund for Creative Research Groups,NSFC,China(81521091)State key infection disease project of China(2017ZX10203208)National Natural Science Foundation of China(81502375,81472691,81672345).
文摘Hepatitis B virus(HBV)infection is still a severe health problem in the world,and chronic hepatitis B(CHB)is the major cause of serious HBV-related complications,including fibrosis,hepatic failure,and hepatocellular carcinoma.It is difficult for CHB patients to achieve complete cure as the currently available antiviral drugs can hardly eradicate covalently closed circular DNA(cccDNA)in the infected liver.Since detecting intrahepatic cccDNA needs invasive procedure,it is urgent to find a noninvasive indicator to reflect the activity of cccDNA.Recently,growing numbers of studies have indicated that serum HBV RNA could be regarded as a new biomarker for CHB activity.In order to illustrate the molecular biology and clinical characteristics of HBV RNA,we systematically reviewed the latest research to summarize the role of HBV RNA in HBV replication and pathogenicity,and to better estimate its potential function as a remarkable biomarker in clinical application.Meanwhile,we will also point out the deficiencies of current research,and discuss the future direction of HBV RNA study.
