Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chine...Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.展开更多
Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metast...Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma(mRCC) who received sorafenib or sunitinib as first-line treatment.Methods:In this single-center,retrospective study,we assessed the progression-free survival(PFS) and overall survival(OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment.PFS and OS were compared between patients with post-treatment hypoalbuminemia(post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level(albumin level≥36.4 g/L).The Memorial Sloan Kettering Cancer Center(MSKCC)risk model stratified mRCC patients into three risk categories.Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models.Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis.Results:The median PFS and OS of the 184 patients were 11 months(95%confidence interval[CI]9-12 months)and 23 months(95%CI 19-33 months),respectively.Patients with post-treatment hypoalbuminemia had significantly shorter median PFS(6 months[95%CI 5-7 months]) and OS(11 months[95%CI 9-15 months]) than patients who had normal post-treatment albumin levels(PFS:12 months[95%CI 11-16 months],P < 0.001;OS:31 months[95%CI24-42 months],P < 0.001),respectively.Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS(hazard ratio[HR],2.113;95%CI 1.390-3.212;P < 0.001) and OS(HR,2.388;95%CI 1.591-3.585;P < 0.001).Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS.The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS(c-index:0.68 and 0.73,respectively) compared with the basic MSKCC risk model(c-index:0.67 and 0.70,respectively).The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis(both P < 0.001).Conclusions:Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors.Additionally,integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.展开更多
With the growing popularity of data-intensive services on the Internet, the traditional process-centric model for business process meets challenges due to the lack of abilities to describe data semantics and dependenc...With the growing popularity of data-intensive services on the Internet, the traditional process-centric model for business process meets challenges due to the lack of abilities to describe data semantics and dependencies, resulting in the inflexibility of the design and implement for the processes. This paper proposes a novel data-aware business process model which is able to describe both explicit control flow and implicit data flow. Data model with dependencies which are formulated by Linear-time Temporal Logic(LTL) is presented, and their satisfiability is validated by an automaton-based model checking algorithm. Data dependencies are fully considered in modeling phase, which helps to improve the efficiency and reliability of programming during developing phase. Finally, a prototype system based on j BPM for data-aware workflow is designed using such model, and has been deployed to Beijing Kingfore heating management system to validate the flexibility, efficacy and convenience of our approach for massive coding and large-scale system management in reality.展开更多
The mineral dust-induced gene(MDIG)comprises a conserved JmjC domain and has the ability to demethylate histone H3 lysine 9 trimethylation(H3K9me3),Previous studies have indicated the significance of MDIG in promoting...The mineral dust-induced gene(MDIG)comprises a conserved JmjC domain and has the ability to demethylate histone H3 lysine 9 trimethylation(H3K9me3),Previous studies have indicated the significance of MDIG in promoting cell proliferation by modulating cell-cycle transition.However,its involvement in liver regeneration has not been extensively investigated.In this study,we generated mice with liver-specific knockout of MDIG and applied partial hepatectomy or carbon tetrachloride mouse models to investigate the biological contribution of MDIG in liver regeneration.展开更多
Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation sig...Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation signature that precisely predicts overall survival(OS)after surgery.Methods:An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing(WGBS)was conducted for two independent cohorts(discovery cohort,n=164;validation cohort,n=170)from three hepatobiliary centers in China.By referring to differentially methylated regions(DMRs),we proposed the concept of prognostically methylated regions(PMRs),which were composed of consecutive prognostically methylated CpGs(PMCs).Using machine learning strategies(Random Forest and the least absolute shrinkage and selector regression),a prognostic methylation score(PMS)was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort.Results:The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74,respectively.In the whole cohort,the PMS was an independent predictor of OS[hazard ratio(HR)=8.12;95% confidence interval(CI):5.48-12.04;P<0.001],and the C-index(0.78)of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine(JHUSM)nomogram(0.69,P<0.001),the Eastern Hepatobiliary Surgery Hospital(EHBSH)nomogram(0.67,P<0.001),American Joint Committee on Cancer(AJCC)tumor-node-metastasis(TNM)staging system(0.61,P<0.001),and MEGNA prognostic score(0.60,P<0.001).The patients in quartile 4 of PMS could benefit from adjuvant therapy(AT)(HR=0.54;95%CI:0.32-0.91;log-rank P=0.043),whereas those in the quartiles 1-3 could not.However,other nomograms and staging system failed to do so.Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors,pathway activation,and immune microenvironment.Conclusions:The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients,and might facilitate decisions in treatment of ICC patients.展开更多
Histone lysine-specific demethylase 1(LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6%(22...Histone lysine-specific demethylase 1(LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6%(224/358) of clear cell renal cell carcinomas(ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage(P ? 0.006), especially tumor stage(P ? 0.017) and lymph node metastasis(P ? 0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival(Po0.001) and recurrence-free survival(Po0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3 K4 demethylation at the CDKN1 A gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in cc RCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.展开更多
Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has ...Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has been seen over the past few decades.Owing to the lack of specific manifestations and tools for early diagnosis,most ICC patients have relatively advanced disease at diagnosis.Thus,neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection.However,even after radical resection,the recurrence rate is relatively high and is a main cause leading to death after surgery,which makes adjuvant therapy necessary.Because of its low incidence,studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy.While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence,some progress has been achieved in recent years.In this review,the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated,and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.展开更多
Dear editor,Renal cancer accounts for approximately 2%of all can-cer deaths worldwide,and renal cell carcinoma(RCC)is the predominant subtype[1].Radiotherapy and chemo-therapy have been found to have limited roles in ...Dear editor,Renal cancer accounts for approximately 2%of all can-cer deaths worldwide,and renal cell carcinoma(RCC)is the predominant subtype[1].Radiotherapy and chemo-therapy have been found to have limited roles in the treatment of RCC.However,the treatment outcomes of metastatic RCC(mRCC)have been improved drastically since the application of molecular targeted therapeutic agents such as tyrosine kinase inhibitors(TKIs).TKIs have been gradually used for the preoperative treatment of RCC.展开更多
Dear editor,The prognosis of metastatic renal cell carcinoma(mRCC)has been significantly improvedwith the development and widespread use of vascular endothelial growth factor(VEGF)pathway inhibitors and mammalian targ...Dear editor,The prognosis of metastatic renal cell carcinoma(mRCC)has been significantly improvedwith the development and widespread use of vascular endothelial growth factor(VEGF)pathway inhibitors and mammalian target of rapamycin(mTOR)pathway inhibitors[1].For the past decade,the standard of care utilized in the first-line setting was VEGF-targeted therapies.Recently,the mRCC treatment landscape has rapidly changed with the exploration of combinations of immune checkpoint inhibitors(ICIs)and anti-VEGF agents[2,3].展开更多
Content-centric network (CCN) is a new Inter- net architecture in which content is treated as the primitive of communication. In CCN, routers are equipped with con- tent stores at the content level, which act as cac...Content-centric network (CCN) is a new Inter- net architecture in which content is treated as the primitive of communication. In CCN, routers are equipped with con- tent stores at the content level, which act as caches for fre- quently requested content. Based on this design, the Internet is available to provide content distribution services without any application-layer support. In addition, as caches are inte- grated into routers, the overall performance of CCN will be deeply affected by the caching efficiency. In this paper, our aim is to gain some insights on how caches should be designed to maintain a high performance in a cost-efficient way. We try to model the two-layer cache hi- erarchy composed of CCN touters using a two-dimensional discrete-time Markov chain, and develop an efficient algo- rithm to calculate the hit ratios of these caches. Simulations validate the accuracy of our modeling method, and convey some meaningful information which can help us better un- derstand the caching mechanism of CCN.展开更多
With technological advances in laparoscopic hepatectomy and new navigation devices,such as flexible laparoscopic ultrasound probes,indocyanine green(ICG)-fluorescent imaging and three-dimensional imaging,laparoscopic ...With technological advances in laparoscopic hepatectomy and new navigation devices,such as flexible laparoscopic ultrasound probes,indocyanine green(ICG)-fluorescent imaging and three-dimensional imaging,laparoscopic segmentectomy(LS),which maximizes the preservation of the functional hepatic reserve and the possibility for future repeat hepatectomy while ensuring adequate surgical margins,has become a feasible alternative to hemihepatectomy for addressing hepatocellular carcinoma(HCC).展开更多
基金supported by the National Natural Science Foundation of China(Nos.81402084,81472378)the Shanghai Municipal Commission of Health and Family Planning(No.2013SY027)the Incubating Program for Clinical Research and Innovation of Renji Hospital(No.PYXJS16-008)
文摘Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.81402084,81472378,and 81672513)incubating program for clinical research and innovation of Renji hospital(Grant No.PYXJS16-008)the Shanghai Municipal Commission of Health and Family Planning(Grant No.2013SY027)
文摘Background:Hypoalbuminemia adversely affects the clinical outcomes of various cancers.The purpose of this study was to estimate the prognostic value of hypoalbuminemia 3-5 weeks after treatment in patients with metastatic renal cell carcinoma(mRCC) who received sorafenib or sunitinib as first-line treatment.Methods:In this single-center,retrospective study,we assessed the progression-free survival(PFS) and overall survival(OS) of 184 mRCC patients who received first-line sorafenib or sunitinib treatment.PFS and OS were compared between patients with post-treatment hypoalbuminemia(post-treatment albumin level <36.4 g/L) and those with normal post-treatment albumin level(albumin level≥36.4 g/L).The Memorial Sloan Kettering Cancer Center(MSKCC)risk model stratified mRCC patients into three risk categories.Prognostic values of all patient characteristics including MSKCC risk category were determined by using univariate and multivariate Cox regression models.Prognostic value was further determined using the Harrell concordance index and receiver operating characteristic curve analysis.Results:The median PFS and OS of the 184 patients were 11 months(95%confidence interval[CI]9-12 months)and 23 months(95%CI 19-33 months),respectively.Patients with post-treatment hypoalbuminemia had significantly shorter median PFS(6 months[95%CI 5-7 months]) and OS(11 months[95%CI 9-15 months]) than patients who had normal post-treatment albumin levels(PFS:12 months[95%CI 11-16 months],P < 0.001;OS:31 months[95%CI24-42 months],P < 0.001),respectively.Multivariate analysis showed that post-treatment hypoalbuminemia was an independent predictor of PFS(hazard ratio[HR],2.113;95%CI 1.390-3.212;P < 0.001) and OS(HR,2.388;95%CI 1.591-3.585;P < 0.001).Post-treatment hypoalbuminemia could also be combined with the MSKCC risk category for better prediction about OS.The model that included post-treatment hypoalbuminemia and MSKCC risk category improved the predictive accuracy for PFS and OS(c-index:0.68 and 0.73,respectively) compared with the basic MSKCC risk model(c-index:0.67 and 0.70,respectively).The prognostic values for PFS and OS of the integrated MSKCC risk model involving post-treatment hypoalbuminemia were significantly more accurate than the basic MSKCC risk model using likelihood ratio analysis(both P < 0.001).Conclusions:Post-treatment hypoalbuminemia can be considered an independent prognostic factor for patients with mRCC who undergo first-line treatment with tyrosine kinase inhibitors.Additionally,integrating post-treatment serum albumin level into the basic MSKCC risk model can improve the accuracy of this model in predicting patient overall survival and progression-free survival.
基金supported by the National Natural Science Foundation of China (No. 61502043, No. 61132001)Beijing Natural Science Foundation (No. 4162042)BeiJing Talents Fund (No. 2015000020124G082)
文摘With the growing popularity of data-intensive services on the Internet, the traditional process-centric model for business process meets challenges due to the lack of abilities to describe data semantics and dependencies, resulting in the inflexibility of the design and implement for the processes. This paper proposes a novel data-aware business process model which is able to describe both explicit control flow and implicit data flow. Data model with dependencies which are formulated by Linear-time Temporal Logic(LTL) is presented, and their satisfiability is validated by an automaton-based model checking algorithm. Data dependencies are fully considered in modeling phase, which helps to improve the efficiency and reliability of programming during developing phase. Finally, a prototype system based on j BPM for data-aware workflow is designed using such model, and has been deployed to Beijing Kingfore heating management system to validate the flexibility, efficacy and convenience of our approach for massive coding and large-scale system management in reality.
基金This work was supported by grants from the National multidisciplinary collaborative diagnosis and treatment capacity building project for major diseases(TJZ202104)the Natural Science Foundation of China(81770615,82070644,82270643,81800564,and 82170621)+1 种基金Science and Technology Major Program of Sichuan Province(2022ZDZX0019 and 2021YFS0048)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC18008 and ZYGD22006)。
文摘The mineral dust-induced gene(MDIG)comprises a conserved JmjC domain and has the ability to demethylate histone H3 lysine 9 trimethylation(H3K9me3),Previous studies have indicated the significance of MDIG in promoting cell proliferation by modulating cell-cycle transition.However,its involvement in liver regeneration has not been extensively investigated.In this study,we generated mice with liver-specific knockout of MDIG and applied partial hepatectomy or carbon tetrachloride mouse models to investigate the biological contribution of MDIG in liver regeneration.
基金supported by The National Key Technologies R&D Program of China(No.2018YFC1106800)The 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18008)The Natural Science Foundation of China(Nos.91859105,81773012,81872004,81802302 and 81902401).
文摘Background:Clinical parameter-based nomograms and staging systems provide limited information for the prediction of survival in intrahepatic cholangiocarcinoma(ICC)patients.In this study,we developed a methylation signature that precisely predicts overall survival(OS)after surgery.Methods:An epigenome-wide study of DNA methylation based on whole-genome bisulfite sequencing(WGBS)was conducted for two independent cohorts(discovery cohort,n=164;validation cohort,n=170)from three hepatobiliary centers in China.By referring to differentially methylated regions(DMRs),we proposed the concept of prognostically methylated regions(PMRs),which were composed of consecutive prognostically methylated CpGs(PMCs).Using machine learning strategies(Random Forest and the least absolute shrinkage and selector regression),a prognostic methylation score(PMS)was constructed based on 14 PMRs in the discovery cohort and confirmed in the validation cohort.Results:The C-indices of the PMS for predicting OS in the discovery and validation cohorts were 0.79 and 0.74,respectively.In the whole cohort,the PMS was an independent predictor of OS[hazard ratio(HR)=8.12;95% confidence interval(CI):5.48-12.04;P<0.001],and the C-index(0.78)of the PMS was significantly higher than that of the Johns Hopkins University School of Medicine(JHUSM)nomogram(0.69,P<0.001),the Eastern Hepatobiliary Surgery Hospital(EHBSH)nomogram(0.67,P<0.001),American Joint Committee on Cancer(AJCC)tumor-node-metastasis(TNM)staging system(0.61,P<0.001),and MEGNA prognostic score(0.60,P<0.001).The patients in quartile 4 of PMS could benefit from adjuvant therapy(AT)(HR=0.54;95%CI:0.32-0.91;log-rank P=0.043),whereas those in the quartiles 1-3 could not.However,other nomograms and staging system failed to do so.Further analyses of potential mechanisms showed that the PMS was associated with tumor biological behaviors,pathway activation,and immune microenvironment.Conclusions:The PMS could improve the prognostic accuracy and identify patients who would benefit from AT for ICC patients,and might facilitate decisions in treatment of ICC patients.
基金supported by the National Nature Science Foundation of China (21472208 and 81625022)
文摘Histone lysine-specific demethylase 1(LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6%(224/358) of clear cell renal cell carcinomas(ccRCC). LSD1 expression was associated with the progression of ccRCC, as indicated by TNM stage(P ? 0.006), especially tumor stage(P ? 0.017) and lymph node metastasis(P ? 0.030). High LSD1 expression proved to be an independent prognostic factor for poor overall survival(Po0.001) and recurrence-free survival(Po0.001) of ccRCC patients. We further show that LSD1 inhibition by siRNA knockdown or using the small molecule inhibitor SP2509 suppressed the growth of ccRCC in vitro and in vivo. Mechanistically, inhibition of LSD1 decreased the H3 K4 demethylation at the CDKN1 A gene promoter, which was associated with P21 upregulation and cell cycle arrest at G1/S in ccRCC cells. Our findings provide new mechanistic insights into the role of LSD1 in cc RCC and suggest the therapeutic potential of LSD1 inhibitors in ccRCC treatment.
基金supported by grants from the National Key Technologies R&D Program(2018YFC1106800)the Natural Science Foundation of China(82002572,82002967,81972747 and 81872004)+1 种基金the fellowship of China National Postdoctoral Program for Innative Talents(BX20200225,BX20200227)the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYJC18008).
文摘Intrahepatic cholangiocarcinoma(ICC)is the second most common primary liver cancer and causes major economic and health burdens throughout the world.Although the incidence of ICC is relatively low,an upward trend has been seen over the past few decades.Owing to the lack of specific manifestations and tools for early diagnosis,most ICC patients have relatively advanced disease at diagnosis.Thus,neoadjuvant therapy is necessary to evaluate tumor biology and downstage these patients so that appropriate candidates can be selected for radical liver resection.However,even after radical resection,the recurrence rate is relatively high and is a main cause leading to death after surgery,which makes adjuvant therapy necessary.Because of its low incidence,studies in both neoadjuvant and adjuvant settings of ICC are lagging compared with other types of malignancy.While standard neoadjuvant and adjuvant regimens are not available in the current guidelines due to a lack of high-level evidence,some progress has been achieved in recent years.In this review,the available literature on advances in neoadjuvant and adjuvant strategies in ICC are evaluated,and possible challenges and opportunities for clinical and translational investigations in the near future are discussed.
基金This study was supported by the research project of Shanghai Science and Technology Commission(18ZR1423200)the Incubating Program for Clinical Research and Innovation of Renji Hospital(PYXJS16-008)the Shen Kang 3-year action plan program(16CR3062B)
文摘Dear editor,Renal cancer accounts for approximately 2%of all can-cer deaths worldwide,and renal cell carcinoma(RCC)is the predominant subtype[1].Radiotherapy and chemo-therapy have been found to have limited roles in the treatment of RCC.However,the treatment outcomes of metastatic RCC(mRCC)have been improved drastically since the application of molecular targeted therapeutic agents such as tyrosine kinase inhibitors(TKIs).TKIs have been gradually used for the preoperative treatment of RCC.
基金supported by Shanghai Science and Technology Commission Research Project(21ZR1438900)the Incubating Program for Clinical Research and Innovation of Renji Hospital(PYXJS16-008,PYIII20-07).
文摘Dear editor,The prognosis of metastatic renal cell carcinoma(mRCC)has been significantly improvedwith the development and widespread use of vascular endothelial growth factor(VEGF)pathway inhibitors and mammalian target of rapamycin(mTOR)pathway inhibitors[1].For the past decade,the standard of care utilized in the first-line setting was VEGF-targeted therapies.Recently,the mRCC treatment landscape has rapidly changed with the exploration of combinations of immune checkpoint inhibitors(ICIs)and anti-VEGF agents[2,3].
文摘Content-centric network (CCN) is a new Inter- net architecture in which content is treated as the primitive of communication. In CCN, routers are equipped with con- tent stores at the content level, which act as caches for fre- quently requested content. Based on this design, the Internet is available to provide content distribution services without any application-layer support. In addition, as caches are inte- grated into routers, the overall performance of CCN will be deeply affected by the caching efficiency. In this paper, our aim is to gain some insights on how caches should be designed to maintain a high performance in a cost-efficient way. We try to model the two-layer cache hi- erarchy composed of CCN touters using a two-dimensional discrete-time Markov chain, and develop an efficient algo- rithm to calculate the hit ratios of these caches. Simulations validate the accuracy of our modeling method, and convey some meaningful information which can help us better un- derstand the caching mechanism of CCN.
基金National Natural Science Foundation of China(No. 81400636)Sichuan Province Key Research and Development Project(No. 2019YFS0203)Key Project of Clinical Research Incubation in West China Hospital of Sichuan University(No. 2020HXFH028)
文摘With technological advances in laparoscopic hepatectomy and new navigation devices,such as flexible laparoscopic ultrasound probes,indocyanine green(ICG)-fluorescent imaging and three-dimensional imaging,laparoscopic segmentectomy(LS),which maximizes the preservation of the functional hepatic reserve and the possibility for future repeat hepatectomy while ensuring adequate surgical margins,has become a feasible alternative to hemihepatectomy for addressing hepatocellular carcinoma(HCC).