We propose a novel high performance carrier stored trench bipolar transistor(CSTBT)with dual shielding structure(DSS-CSTBT).The proposed DSS-CSTBT features a double trench structure with different trench profiles in t...We propose a novel high performance carrier stored trench bipolar transistor(CSTBT)with dual shielding structure(DSS-CSTBT).The proposed DSS-CSTBT features a double trench structure with different trench profiles in the surface,in which a shallow gate trench is shielded by a deep emitter trench and a thick oxide layer under it.Compared with the conventional CSTBT(con-CSTBT),the proposed DSS-CSTBT not only alleviates the negative impact of the shallow gate trench and highly doped CS layer on the breakdown voltage(BV),but also well reduces the gate-collector capacitance CGC,gate charge Q_(G),and turn-off loss E_(OFF)of the device.Furthermore,lower turn-on loss E_(ON)and gate drive loss E_(DR)are also obtained.Simulation results show that with the same CS layer doping concentration N_(CS)=1.5×10^(16)cm^(-3),the BV increases from 1312 V of the con-CSTBT to 1423 V of the proposed DSS-CSTBT with oxide layer thickness under gate(T_(og2))of 1μm.Moreover,compared with the con-CSTBT,the C_(GC)at V_(CE)of 25 V and miller plateau charge(Q_(GC))for the proposed DSS-CSTBT with T_(og2)of 1μm are reduced by 79.4%and 74.3%,respectively.With the VGEincreases from 0 V to 15 V,the total QGfor the proposed DSS-CSTBT with T_(og2)of 1μm is reduced by 49.5%.As a result,at the same on-state voltage drop(V_(CEON))of 1.55 V,the E_(ON)and E_(OFF)are reduced from 20.3 mJ/cm^(2)and 19.3 mJ/cm^(2)for the con-CSTBT to8.2 mJ/cm^(2)and 9.7 mJ/cm^(2)for the proposed DSS-CSTBT with T_(og2)of 1μm,respectively.The proposed DSS-CSTBT not only significantly improves the trade-off relationship between the V_(CEON)and E_(OFF)but also greatly reduces the E_(ON).展开更多
A novel silicon carbide(SiC) trench metal–oxide–semiconductor field-effect transistor(MOSFET) with a dual shield gate(DSG) and optimized junction field-effect transistor(JFET) layer(ODSG-TMOS) is proposed. The combi...A novel silicon carbide(SiC) trench metal–oxide–semiconductor field-effect transistor(MOSFET) with a dual shield gate(DSG) and optimized junction field-effect transistor(JFET) layer(ODSG-TMOS) is proposed. The combination of the DSG and optimized JFET layer not only significantly improves the device’s dynamic performance but also greatly enhances the safe operating area(SOA). Numerical analysis is carried out with Silvaco TCAD to study the performance of the proposed structure. Simulation results show that comparing with the conventional asymmetric trench MOSFET(Con-ATMOS), the specific on-resistance(Ron,sp) is significantly reduced at almost the same avalanche breakdown voltage(BVav). Moreover, the DSG structure brings about much smaller reverse transfer capacitance(Crss) and input capacitance(Ciss), which helps to reduce the gate–drain charge(Qgd) and gate charge(Qg). Therefore, the high frequency figure of merit(HFFOM) of Ron,sp·Qgdand Ron,sp· Qgfor the proposed ODSG-TMOS are improved by 83.5% and 76.4%, respectively.The switching power loss of the proposed ODSG-TMOS is 77.0% lower than that of the Con-ATMOS. In addition, the SOA of the proposed device is also enhanced. The saturation drain current(Id,sat) at a gate voltage(Vgs) of 15 V for the ODSGTMOS is reduced by 17.2% owing to the JFET effect provided by the lower shield gate(SG) at a large drain voltage. With the reduced Id,sat, the short-circuit withstand time is improved by 87.5% compared with the Con-ATMOS. The large-current turn-off capability is also improved, which is important for the widely used inductive load applications.展开更多
BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate...BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.展开更多
AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China ...AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.展开更多
Background and Objective: S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on ...Background and Objective: S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on breast cancer, liver cancer and colon carcinoma. This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro, and the antitumor mechanisms. Methods: The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 μmol/(kg·day)], high concentration group [768 μmol/(kg·day)], and control group [normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP. Results: SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51± 149.27) mm3] and high concentration group [(444.32 ± 118.51) mm3] than in control group [(1018.22 ± 223.07) mm3] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment. Conclusions: SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.展开更多
Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets fo...Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets for ESCC.The datasets GSE44021,GSE77861,GSE20347,and GSE29001 retrieved from the Gene Expression Omnibus(GEO)database contained 117 ESCC tissues and 109 normal tissues.Differentially expressed genes(DEGs)associated with ESCC were identified using the GEO2R tool.Dysregulated pathways associated with ESCC mainly included mitotic regulation,cell cycle,ECM-receptor interaction,DNA replication,etc.The protein-protein interaction(PPI)network of overlapping DEGs was constructed and nine key genes(KGs)were identified from the complex interaction network using Degree,maximum neighborhood component(MNC),and maximal clique centrality(MCC)algorithms.Expression patterns of KGs at the transcriptional and translational levels were validated using ESCC-related data from the Cancer Genome Atlas(TCGA),Oncomine,and Human Protein Atlas(HPA)databases.Genetic alterations calculation,immune cell infiltrates evaluation,methylation analysis,prognostic analysis,transcription factors(TFs)and miRNAs regulatory networks construction,and targeted drug prediction were further performed.It was also found that the knockout of these KGs affected the survival of more than two types of ESCC cells by genome-wide CRISPR-Cas9 dropout screens.In conclusion,we identified KGs,TFs,and miRNAs with biomarker potential(e.g.,NDC80,BUB1,TOP2A,AURKA,AURKB,TTK,UBE2C,TPX2,BUB1B,E2F1,and hsa-miR-483-5p)and 23 candidate targeted drugs for ESCC by utilizing an integrated multi-omics approach.These findings provide additional insights into uncovering the molecular mechanism and improving the efficiency of clinical diagnosis and treatment for ESCC.展开更多
基金the Shenzhen Science and Technology Project,China(No.JCYJ20190809162401686)the Guangdong Basic and Applied Basic Research Foundation,China(No.2020A1515010069).
基金the National Key Research and Development Program of China(Grant No.2018YFB1201802)the Key Realm R&D Program of Guangdong Province,China(Grant No.2018B010142001)the Guangdong Basic and Applied Basic Research Foundation,China(Grant No.2020A1515010128).
文摘We propose a novel high performance carrier stored trench bipolar transistor(CSTBT)with dual shielding structure(DSS-CSTBT).The proposed DSS-CSTBT features a double trench structure with different trench profiles in the surface,in which a shallow gate trench is shielded by a deep emitter trench and a thick oxide layer under it.Compared with the conventional CSTBT(con-CSTBT),the proposed DSS-CSTBT not only alleviates the negative impact of the shallow gate trench and highly doped CS layer on the breakdown voltage(BV),but also well reduces the gate-collector capacitance CGC,gate charge Q_(G),and turn-off loss E_(OFF)of the device.Furthermore,lower turn-on loss E_(ON)and gate drive loss E_(DR)are also obtained.Simulation results show that with the same CS layer doping concentration N_(CS)=1.5×10^(16)cm^(-3),the BV increases from 1312 V of the con-CSTBT to 1423 V of the proposed DSS-CSTBT with oxide layer thickness under gate(T_(og2))of 1μm.Moreover,compared with the con-CSTBT,the C_(GC)at V_(CE)of 25 V and miller plateau charge(Q_(GC))for the proposed DSS-CSTBT with T_(og2)of 1μm are reduced by 79.4%and 74.3%,respectively.With the VGEincreases from 0 V to 15 V,the total QGfor the proposed DSS-CSTBT with T_(og2)of 1μm is reduced by 49.5%.As a result,at the same on-state voltage drop(V_(CEON))of 1.55 V,the E_(ON)and E_(OFF)are reduced from 20.3 mJ/cm^(2)and 19.3 mJ/cm^(2)for the con-CSTBT to8.2 mJ/cm^(2)and 9.7 mJ/cm^(2)for the proposed DSS-CSTBT with T_(og2)of 1μm,respectively.The proposed DSS-CSTBT not only significantly improves the trade-off relationship between the V_(CEON)and E_(OFF)but also greatly reduces the E_(ON).
基金Project supported by the China Postdoctoral Science Foundation (Grant No. 2020M682607)。
文摘A novel silicon carbide(SiC) trench metal–oxide–semiconductor field-effect transistor(MOSFET) with a dual shield gate(DSG) and optimized junction field-effect transistor(JFET) layer(ODSG-TMOS) is proposed. The combination of the DSG and optimized JFET layer not only significantly improves the device’s dynamic performance but also greatly enhances the safe operating area(SOA). Numerical analysis is carried out with Silvaco TCAD to study the performance of the proposed structure. Simulation results show that comparing with the conventional asymmetric trench MOSFET(Con-ATMOS), the specific on-resistance(Ron,sp) is significantly reduced at almost the same avalanche breakdown voltage(BVav). Moreover, the DSG structure brings about much smaller reverse transfer capacitance(Crss) and input capacitance(Ciss), which helps to reduce the gate–drain charge(Qgd) and gate charge(Qg). Therefore, the high frequency figure of merit(HFFOM) of Ron,sp·Qgdand Ron,sp· Qgfor the proposed ODSG-TMOS are improved by 83.5% and 76.4%, respectively.The switching power loss of the proposed ODSG-TMOS is 77.0% lower than that of the Con-ATMOS. In addition, the SOA of the proposed device is also enhanced. The saturation drain current(Id,sat) at a gate voltage(Vgs) of 15 V for the ODSGTMOS is reduced by 17.2% owing to the JFET effect provided by the lower shield gate(SG) at a large drain voltage. With the reduced Id,sat, the short-circuit withstand time is improved by 87.5% compared with the Con-ATMOS. The large-current turn-off capability is also improved, which is important for the widely used inductive load applications.
文摘BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1)and microalbuminuria in newly diagnosed T2DM patients.METHODS In total,760 patients were recruited for this cross-sectional study.The GLP-1 levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were determined.RESULTS Patients with microalbuminuria exhibited lower GLP-1 levels at 30 min and 120 min during a standard meal test than patients with normal albuminuria(30 min GLP-1,16.7±13.3 pmol vs 19.9±15.6 pmol,P=0.007;120 min GLP-1,16.0±14.1 pmol vs 18.4±13.8 pmol,P=0.037).The corresponding area under the curve for active GLP-1(AUCGLP-1)was also lower in microalbuminuria patients(2257,1585 to 3506 vs 2896,1763 to 4726,pmol×min,P=0.003).Postprandial GLP-1 levels at 30 min and 120 min and AUCGLP-1 were negatively correlated with the UACR(r=0.159,r=0.132,r=0.206,respectively,P<0.001).The prevalence of microalbuminuria in patients with newly diagnosed T2DM was 21.7%,which decreased with increasing quartiles of AUCGLP-1 levels(27.4%,25.3%,18.9%and 15.8%).After logistic regression analysis adjusted for sex,age,hemoglobin A1c,body mass index,systolic blood pressure,estimated glomerular filtration rate,homeostasis model assessment of insulin resistance,AUC_(glucose)and AUC_(glucagon)patients in quartile 4 of the AUCGLP-1 presented a lower risk of microalbuminuria compared with the patients in quartile 1(odds ratio=0.547,95%confidence interval:0.325-0.920,P=0.01).A consistent association was also found between 30 min GLP-1 or 120 min GLP-1 and microalbuminuria.CONCLUSION Postprandial GLP-1 levels were independently associated with microalbuminuria in newly diagnosed Chinese T2DM patients.
基金Supported by National Natural Science Foundation of China,No.81160352grants from the Education Department Foundation of Yunnan Province,No.2012J091+1 种基金Health Bureau of Yunnan Province,No.D-201203(partly)Science and Technology Department of Yunnan Province,No.2013HB084(partly)
文摘AIM:To analyze the hepatitis B virus(HBV) characters in China,as well as the correlation between several HBV mutation and hepatitis symptoms.METHODS:A total of 1148 HBV genome sequences from patients throughout China were collected via the National Center For Biotechnology Information database(information including:genotype,territory and clinical status).HBV genotypes were classified by a direct reference from the Genbank sequence annotation,phylogenetic tree and online software analysis(http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.cgi).The phylogenetic tree was constructed based on the neighbor-joining method by MEGA5.0 software.HBV sequences were grouped based on phylogenetic tree and the distance between the groups was calculated by using the computer between group mean distance methods.Seven hundred and twelve HBV sequences with clear annotation of clinical symptoms were selected to analyses the correlation of mutation and clinical symptoms.Characteristics of sequences were analyzed by using DNAStar and BioEdit software packages.The codon usage bias and RNA secondary structures analysis were performed by RNAdraw software.Recombination analysis was performed by using Simplot software.RESULTS:In China,HBV genotype C was the predominant in Northeastern,genotype B was predominant in Central Southern areas,genotype B and C were both dominant in Southwestern areas,and the recombinant genotype C/D was predominant in Northwestern areas.C2 and B2 were identified as the two major sub-genotypes,FJ386674 might be a putative sub-genotype as B10.The basal core promoter double mutation and pre-C mutation showed various significant differences between hepatitis symptoms.In addition to ATG,many other HBV initiation codons also exist.HBV has codon usage bias;the termination codon of X,C and P open reading frames(ORF) were TAA,TAG,and TGA,respectively.The major stop codons of S-ORF were TAA(96.45%) and TGA(83.60%) in B2 and C2 subtype,respectively.CONCLUSION:This study recapitulated the epidemiology of HBV in China,and the information might be meaningful critical for the future prevention and therapy of HBV infections.
文摘Background and Objective: S-adenosylmethionine (SAM), the most important methyl donor in human body, is generally used to treat cholestasis in clinic. In recent years, SAM has been found to have inhibitory effects on breast cancer, liver cancer and colon carcinoma. This study was to investigate the inhibitory effects of SAM on human gastric cancer cells in vivo and in vitro, and the antitumor mechanisms. Methods: The effects of SAM on the proliferation of gastric cancer SGC-7901 and MKN-45 cells were determined by MTT assay. After SGC-7901 and MKN-45 cells were treated with 0, 2, and 4 mmol/L SAM for 72 h, the expression and methylation of c-myc and urokinase type plasminogen activator (uPA) were detected by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP). Tumor xenografts were established by injecting SGC-7901 cells subcutaneously in BALB/c nude mice. The mice were randomized into low concentration group [192 μmol/(kg·day)], high concentration group [768 μmol/(kg·day)], and control group [normal saline (NS)], and received peritoneal injection of relative reagents for 15 days. The tumor size was measured, the protein and mRNA expression of c-myc and uPA were detected by immunohistochemistry and RT-PCR, and the methylation of c-myc and uPA genes was detected by MSP. Results: SAM inhibited the growth of SGC-7901 and MKN-45 cells obviously and the effects were enhanced with the increase of SAM concentration and treatment time. The mRNA expression of c-myc and uPA in SGC-7901 cells and that of uPA in MKN-45 cells significantly decreased. The c-myc and uPA genes in SGC-7901 cells and uPA gene in MKN-45 cells were partly or completely methylated after SAM treatment. The tumor volume was significantly lower in low concentration group [(618.51± 149.27) mm3] and high concentration group [(444.32 ± 118.51) mm3] than in control group [(1018.22 ± 223.07) mm3] (both P < 0.01). The inhibitory rates of tumor growth were 39.26% in low concentration group and 56.36% in high concentration group. The protein and mRNA expressions of c-myc and uPA were remarkably reduced (all P < 0.01), and the hypomethylation of c-myc and uPA genes were reversed after SAM treatment. Conclusions: SAM can inhibit the growth of human gastric cancer cells both in vivo and in vitro. The mechanism may be that SAM can reverse the hypomethylation of c-myc and uPA genes, reduce their expression, and then inhibit tumor growth.
基金supported by the Innovation Capacity Building Project of the Jilin Provincial Development and Reform Commission(2021C041-1).
文摘Esophageal squamous cell carcinoma(ESCC),the major subtype of esophageal carcinoma(ESCA),is one of the most lethal malignancies worldwide.This study aimed to identify potential biomarkers and/or therapeutic targets for ESCC.The datasets GSE44021,GSE77861,GSE20347,and GSE29001 retrieved from the Gene Expression Omnibus(GEO)database contained 117 ESCC tissues and 109 normal tissues.Differentially expressed genes(DEGs)associated with ESCC were identified using the GEO2R tool.Dysregulated pathways associated with ESCC mainly included mitotic regulation,cell cycle,ECM-receptor interaction,DNA replication,etc.The protein-protein interaction(PPI)network of overlapping DEGs was constructed and nine key genes(KGs)were identified from the complex interaction network using Degree,maximum neighborhood component(MNC),and maximal clique centrality(MCC)algorithms.Expression patterns of KGs at the transcriptional and translational levels were validated using ESCC-related data from the Cancer Genome Atlas(TCGA),Oncomine,and Human Protein Atlas(HPA)databases.Genetic alterations calculation,immune cell infiltrates evaluation,methylation analysis,prognostic analysis,transcription factors(TFs)and miRNAs regulatory networks construction,and targeted drug prediction were further performed.It was also found that the knockout of these KGs affected the survival of more than two types of ESCC cells by genome-wide CRISPR-Cas9 dropout screens.In conclusion,we identified KGs,TFs,and miRNAs with biomarker potential(e.g.,NDC80,BUB1,TOP2A,AURKA,AURKB,TTK,UBE2C,TPX2,BUB1B,E2F1,and hsa-miR-483-5p)and 23 candidate targeted drugs for ESCC by utilizing an integrated multi-omics approach.These findings provide additional insights into uncovering the molecular mechanism and improving the efficiency of clinical diagnosis and treatment for ESCC.