Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevale...According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevalent cancer,following only after lung cancer(2).The first version of the Chinese Society of Clinical Oncology(CSCO)guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research,drug accessibility and expert consensus(3-8).Here,we present the main updates of the 2024 version compared to the 2023 version.展开更多
[Objectives]To investigate the effects of 15 distinct citrus rootstock-scion combinations on tree growth,fruit quality,and photosynthetic characteristics under red loam soil conditions and provide a theoretical founda...[Objectives]To investigate the effects of 15 distinct citrus rootstock-scion combinations on tree growth,fruit quality,and photosynthetic characteristics under red loam soil conditions and provide a theoretical foundation for the selection of appropriate citrus rootstock-scion combinations in the Zhaoqing region.[Methods]A total of 15 citrus rootstock-scion combinations were utilized as test materials for a comprehensive analysis of their phenological periods(budding,flowering,and fruiting),tree growth indicators(tree height,crown diameter,and growth),and fruit quality(appearance quality and intrinsic quality).The photosynthetic characteristics of the test materials,including the net photosynthetic rate(Pn),transpiration rate(Tr),water use efficiency(WUE),apparent quantum yield(AQY),and carboxylation efficiency(CE),were analyzed to determine their significance.Additionally,the leaf photosynthetic physiological indicators,such as soluble protein,specific leaf weight,chlorophyll,and carotenoids,were evaluated.[Results]There were notable differences observed in the phenological period,growth potential of trees,fruit quality,and photosynthetic characteristics among various citrus rootstock-scion combinations.The phenological periods exhibited variation contingent on the grafting varieties.In terms of tree growth potential,the Citrus tangerina Tanaka‘Hongju’and C.haniana Hort.‘Suanju’rootstocks demonstrated greater tree height,crown growth,and overall tree strength;however,they were also prone to excessive growth.Conversely,the C.limonia Osbeck‘Hongningmeng’and C.sinensis×P.trifoliata‘Zhicheng’rootstocks displayed medium growth potential,while the Poncirus trifoliate(L)Raf.‘Zhike’rootstock resulted in shorter trees.In terms of fruit quality,the single fruit weight of C.flamea Hort.‘Shatangju’ranged from 33 to 50 g,exhibiting a flat and round shape.The total soluble solids and titratable acid content of‘Shatangju’grafted onto the‘Zhike’rootstock were notably high.In contrast,the single fruit weight of C.haniana Hort.‘Chuntianju’varied between 65 and 81 g,characterized by a high flat round shape.The‘Suanju’rootstock demonstrated a higher sugar and acid content compared to other rootstocks.Additionally,the single fruit weight of C.nobilis Lour.‘Gonggan’ranged from 62 to 145 g,with the fruit shape being either round or oval.The soluble sugar and total soluble solids content associated with the‘Zhike’rootstock was also elevated.In relation to photosynthetic characteristics,the photosynthetic performance of the‘Shatangju’variety was superior when grafted onto the‘Zhike’and‘Hongju’rootstocks.Similarly,the‘Chuntianju’variety exhibited enhanced photosynthetic performance on the‘Zhike’,‘Zhicheng’,and‘Hongju’rootstocks.Furthermore,the‘Gonggan’variety demonstrated improved photosynthetic performance when grafted onto the‘Zhike’and‘Suanju’rootstocks.[Conclusions]Based on the characteristics of the red loam soil in the Zhaoqing region,the rootstocks‘Zhike’and‘Hongju’are conducive to the cultivation of the‘Shatangju’variety.Additionally,the rootstocks‘Zhike’,‘Zhicheng’,and‘Hongju’are optimal for the growth of the‘Chuntianju’variety,while the rootstocks‘Zhike’and‘Suanju’are appropriate for the growth of the‘Gonggan’variety.展开更多
Colorectal cancer(CRC)is the second most common cancer and the most common type of gastrointestinal cancer with rapidly increasing incidence and mortality in China(1,2).Since the first edition of the Chinese Society o...Colorectal cancer(CRC)is the second most common cancer and the most common type of gastrointestinal cancer with rapidly increasing incidence and mortality in China(1,2).Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guideline was published in2017,the guideline has been updated annually according to the latest results of clinical research at home and abroad,the accessibility of drugs and the opinions of CSCO experts(3-7).展开更多
The fruit peel color is a crucial trait of cucumber.To better understand the molecular mechanisms underlying cucumber peel coloration,we compared the UPLC-ESI-MS/MS-based flavonoid metabolomic and RNA sequencing-based...The fruit peel color is a crucial trait of cucumber.To better understand the molecular mechanisms underlying cucumber peel coloration,we compared the UPLC-ESI-MS/MS-based flavonoid metabolomic and RNA sequencing-based transcriptomic profiling of the brown peeled cucumber line‘PW’at six developmental stages.A total of 210 flavonoid metabolites were identified.Of which,117 flavonoid metabolites were differentially accumulated.In this study,weighted gene co-expression network analysis combined with Kyoto Encyclopedia of Gene and Genomes enrichment analysis revealed key genes coding for seven enzymes and eight transcription factors(TFs)associated with flavonoid biosynthesis.Among them,the R2R3MYB CsaV3_4G001130 is the best candidate gene that is responsible for controlling mature fruit colors in cucumber.Sanger sequencing revealed one nonsynonymous SNP in the exon of CsaV3_4G001130 among the selected 11 cucumber lines,which introduced a premature stop codon,generating a truncated protein in pale yellow or creamy peeled fruits.Yeast two-hybrid assays showed a direct interaction of CsaV3_4G001130 with the bHLH TF CsaV3_1G002260 and the WD40 protein CsaV3_5G001800.However,the interactions were influenced by the nonsynonymous SNP we identified.Our finding revealed that the integrated transcriptome and metabolome analysis further demonstrated that the abundance of some pigmented flavonoids(especially anthocyanins and chalcones)contributed to the coloration of‘PW’fruits.These findings pave the way for elucidation of flavonoid biosynthesis and improvement of cucumber peel color in the future.展开更多
The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance.However,the genetic basis of muscle development in the Boer goat remains ...The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance.However,the genetic basis of muscle development in the Boer goat remains obscure.In this study,we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development.A total of9 959 autosomal copy number variations(CNVs) were identified through selection signal analysis in 127 goat genomes.Specifically,we confirmed that the highest signal CNV(HSV) was a chromosomal arrangement containing an approximately 1.11 Mb(CHIR17:60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region(CHIR17:60145940-60151302 bp) with overlapping genes(e.g.,ARHGAP10,NR3C2,EDNRA,PRMT9,and TMEM184C).The homozygous duplicated HSV genotype(+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats.The expression network of three candidate genes(ARHGAP10,NR3C2,and EDNRA)regulating dose transcription was constructed by RNA sequencing.Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells(SMSCs) and their overexpression significantly increased the expression of SAA3.The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.展开更多
The time-sequenced damage behavior of the reactive projectile impacting double-layer plates is discussed.The analytical model considering the combined effect of kinetic and chemical energy is developed to reveal the d...The time-sequenced damage behavior of the reactive projectile impacting double-layer plates is discussed.The analytical model considering the combined effect of kinetic and chemical energy is developed to reveal the damage mechanism.The influences of impact velocity and reactive projectile chemical characteristics on the damage effect are decoupled analyzed based on this model.These analyses indicate that the high energy releasing efficiency and fast reaction propagation velocity of the reactive projectile are conducive to enhancing the damage effect.The experiments with various reactive projectiles impact velocity increasing from 702 to 1385 m/s were conducted to verify this model.The experimental results presented that,the damage hole radius of the rear-plate increases with the increase of impact velocity.At the impact velocity of 1350 m/s,the radius of damage hole formed by PTFE/Al/Bi_(2)O_(3),PTFE/Al/MoO_(3),PTFE/Al/Fe_(2)O_(3)projectile on the rear-plate become smaller in sequence.These results are consistent with the analytical model prediction,demonstrating that this model can predict the damage effect quantitatively.This work is of constructive significance to the application of reactive projectiles.展开更多
Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of present...Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).展开更多
The colon is derived from the embryological midgut and hindgut separately,with the right colon and left colon having different features with regards to both anatomical and physiological characteristics.Cancers located...The colon is derived from the embryological midgut and hindgut separately,with the right colon and left colon having different features with regards to both anatomical and physiological characteristics.Cancers located in the right and left colon are referred to as right colon cancer(RCC) and left colon cancer(LCC),respectively,based on their apparent anatomical positions.Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC,but molecular features also vary between them,not to mention the distinguishing clinical manifestations.Disease-free survival after radical surgery of both RCC and LCC are similar.In the treatment of RCC,the benefit gained from adjuvant FOLFIRI chemotherapy is superior,or at least similar,to LCC,but inferior to LCC if FOLFOX regimen is applied.On the other hand,metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting.For KRAS wild-type cancers,LCC benefits more from cetuximab treatment than RCC.Moreover,advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC.Significant varieties exist at the molecular level between RCC and LCC,which may serve as the cause of all apparent differences.With respect to carcinogenesis mechanisms,RCC is associated with known gene types,such as MMR,KRAS,BRAF,and mi RNA-31,while LCC is associated with CIN,p53,NRAS,mi RNA-146 a,mi RNA-147 b,and mi RNA-1288.Regarding protein expression,RCC is related to GNAS,NQO1,telomerase activity,P-PDH,and annexin A10,while LCC is related to Topo I,TS,and EGFR.In addition,separated pathways dominate progressionto relapse in RCC and LCC.Therefore,RCC and LCC should be regarded as two heterogeneous entities,with this heterogeneity being used to stratify patients in order for them to have the optimal,current,and novel therapeutic strategies in clinical practice.Additional research is needed to uncover further differences between RCC and LCC.展开更多
AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univari...AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). CONCLUSION:The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage Ⅲ CRC patients.展开更多
AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Gen...AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.展开更多
AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after rad...AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.展开更多
AIM: To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1 ) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion.METHODS: Immunohistochemistry was used...AIM: To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1 ) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion.METHODS: Immunohistochemistry was used to detect the protein expression of SATB1 in 30 colorectal cancer (CRC) tissue samples and pair-matched adjacent nontumor samples. Cell growth was investigated after enhancing expression of SATB1. Wound-healing assay and Transwell assay were used to investigate the impact of SATB1 on migratory and invasive abilities of SW480 cells in vitro . Nude mice that received subcutaneous implantation or lateral tail vein were used to study the effects of SATB1 on tumor growth or metastasis in vivo . RESULTS: SATB1 was over-expressed in CRC tissues and CRC cell lines. SATB1 promotes cell proliferation and cell cycle progression in CRC SW480 cells. SATB1 over-expression could promote cell growth in vivo . In addition, SATB1 could significantly raise the ability of cell migration and invasion in vitro and promote the ability of tumor metastasis in vivo . SATB1 could up-regulate matrix metalloproteases 2, 9, cyclin D1 and vimentin, meanwhile SATB1 could down-regulate E-cadherin in CRC. CONCLUSION: SATB1 acts as a potential growth and metastasis promoter in CRC. SATB1 may be useful as a therapeutic target for CRC.展开更多
Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,...Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,100 deaths of CRC in China, accounting for 9.87% and 8.01% of all malignancies. The first version of the Chinese Society of Clinical Oncology(CSCO) guidelines was released in April2017, and has been updated annually based on the latest clinical research data and the availability of new drugs(2-4). Here, we present the main updates of the 2021 version compared to 2020 version.展开更多
The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase I...The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.展开更多
Colorectal cancer(CRC) is the third most common cancer worldwide and the second most common in tumor-related mortality by Global Cancer Statistics 2020(1). Recent data show that the incidence and mortality of CRC in C...Colorectal cancer(CRC) is the third most common cancer worldwide and the second most common in tumor-related mortality by Global Cancer Statistics 2020(1). Recent data show that the incidence and mortality of CRC in China are increasing(2-4), with the number of new cases and deaths reaching 607,900 and 261,777 in 2019.展开更多
Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant pr...Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.展开更多
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
基金supported by the Provincial Key R&D Program of Zhejiang Province(No.2021C03125)National Natural Science Foundation of China(No.82373415 and No.82302489)Beijing Xisike Clinical Oncology Research Foundation(No.Y-tongshu2021/ms-0003).
文摘According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevalent cancer,following only after lung cancer(2).The first version of the Chinese Society of Clinical Oncology(CSCO)guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research,drug accessibility and expert consensus(3-8).Here,we present the main updates of the 2024 version compared to the 2023 version.
基金Supported by Earmarked Fund for China Agriculture Research System(CARS-26)Project of High-quality Development in Hundred Counties,Thousands Towns and Ten Thousand Villages.
文摘[Objectives]To investigate the effects of 15 distinct citrus rootstock-scion combinations on tree growth,fruit quality,and photosynthetic characteristics under red loam soil conditions and provide a theoretical foundation for the selection of appropriate citrus rootstock-scion combinations in the Zhaoqing region.[Methods]A total of 15 citrus rootstock-scion combinations were utilized as test materials for a comprehensive analysis of their phenological periods(budding,flowering,and fruiting),tree growth indicators(tree height,crown diameter,and growth),and fruit quality(appearance quality and intrinsic quality).The photosynthetic characteristics of the test materials,including the net photosynthetic rate(Pn),transpiration rate(Tr),water use efficiency(WUE),apparent quantum yield(AQY),and carboxylation efficiency(CE),were analyzed to determine their significance.Additionally,the leaf photosynthetic physiological indicators,such as soluble protein,specific leaf weight,chlorophyll,and carotenoids,were evaluated.[Results]There were notable differences observed in the phenological period,growth potential of trees,fruit quality,and photosynthetic characteristics among various citrus rootstock-scion combinations.The phenological periods exhibited variation contingent on the grafting varieties.In terms of tree growth potential,the Citrus tangerina Tanaka‘Hongju’and C.haniana Hort.‘Suanju’rootstocks demonstrated greater tree height,crown growth,and overall tree strength;however,they were also prone to excessive growth.Conversely,the C.limonia Osbeck‘Hongningmeng’and C.sinensis×P.trifoliata‘Zhicheng’rootstocks displayed medium growth potential,while the Poncirus trifoliate(L)Raf.‘Zhike’rootstock resulted in shorter trees.In terms of fruit quality,the single fruit weight of C.flamea Hort.‘Shatangju’ranged from 33 to 50 g,exhibiting a flat and round shape.The total soluble solids and titratable acid content of‘Shatangju’grafted onto the‘Zhike’rootstock were notably high.In contrast,the single fruit weight of C.haniana Hort.‘Chuntianju’varied between 65 and 81 g,characterized by a high flat round shape.The‘Suanju’rootstock demonstrated a higher sugar and acid content compared to other rootstocks.Additionally,the single fruit weight of C.nobilis Lour.‘Gonggan’ranged from 62 to 145 g,with the fruit shape being either round or oval.The soluble sugar and total soluble solids content associated with the‘Zhike’rootstock was also elevated.In relation to photosynthetic characteristics,the photosynthetic performance of the‘Shatangju’variety was superior when grafted onto the‘Zhike’and‘Hongju’rootstocks.Similarly,the‘Chuntianju’variety exhibited enhanced photosynthetic performance on the‘Zhike’,‘Zhicheng’,and‘Hongju’rootstocks.Furthermore,the‘Gonggan’variety demonstrated improved photosynthetic performance when grafted onto the‘Zhike’and‘Suanju’rootstocks.[Conclusions]Based on the characteristics of the red loam soil in the Zhaoqing region,the rootstocks‘Zhike’and‘Hongju’are conducive to the cultivation of the‘Shatangju’variety.Additionally,the rootstocks‘Zhike’,‘Zhicheng’,and‘Hongju’are optimal for the growth of the‘Chuntianju’variety,while the rootstocks‘Zhike’and‘Suanju’are appropriate for the growth of the‘Gonggan’variety.
基金supported by the Provincial Key R&D Program of Zhejiang Province(No.2021C03125)Beijing Xisike Clinical Oncology Research Foundation(No.Y-tongshu2021/ms-0003)。
文摘Colorectal cancer(CRC)is the second most common cancer and the most common type of gastrointestinal cancer with rapidly increasing incidence and mortality in China(1,2).Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guideline was published in2017,the guideline has been updated annually according to the latest results of clinical research at home and abroad,the accessibility of drugs and the opinions of CSCO experts(3-7).
基金The‘JBGS’Project of Seed Industry Revitalization in Jiangsu Province[Grant No.JBGS(2021)018]the Jiangsu Agricultural Innovation of New Cultivars(Grant No.PZCZ201720)+2 种基金the Jiangsu Agriculture Science and Technology Innovation Fund[Grant No.CX(20)3103]the Open Project Program of Jiangsu Key Laboratory for Horticultural Crop Genetic Improvement(Grant No.K2020030)the Open Project Program of Joint International Research Laboratory of Agriculture and Agri-Product Safety,the Ministry of Education of China(Grant No.JILAR-KF202001).
文摘The fruit peel color is a crucial trait of cucumber.To better understand the molecular mechanisms underlying cucumber peel coloration,we compared the UPLC-ESI-MS/MS-based flavonoid metabolomic and RNA sequencing-based transcriptomic profiling of the brown peeled cucumber line‘PW’at six developmental stages.A total of 210 flavonoid metabolites were identified.Of which,117 flavonoid metabolites were differentially accumulated.In this study,weighted gene co-expression network analysis combined with Kyoto Encyclopedia of Gene and Genomes enrichment analysis revealed key genes coding for seven enzymes and eight transcription factors(TFs)associated with flavonoid biosynthesis.Among them,the R2R3MYB CsaV3_4G001130 is the best candidate gene that is responsible for controlling mature fruit colors in cucumber.Sanger sequencing revealed one nonsynonymous SNP in the exon of CsaV3_4G001130 among the selected 11 cucumber lines,which introduced a premature stop codon,generating a truncated protein in pale yellow or creamy peeled fruits.Yeast two-hybrid assays showed a direct interaction of CsaV3_4G001130 with the bHLH TF CsaV3_1G002260 and the WD40 protein CsaV3_5G001800.However,the interactions were influenced by the nonsynonymous SNP we identified.Our finding revealed that the integrated transcriptome and metabolome analysis further demonstrated that the abundance of some pigmented flavonoids(especially anthocyanins and chalcones)contributed to the coloration of‘PW’fruits.These findings pave the way for elucidation of flavonoid biosynthesis and improvement of cucumber peel color in the future.
基金supported by the National Natural Science Foundation of China (32272834)。
文摘The Boer goat is one of the top meat breeds in modern animal husbandry and has attracted widespread attention for its unique growth performance.However,the genetic basis of muscle development in the Boer goat remains obscure.In this study,we identified specific structural variants in the Boer goat based on genome-wide selection signals and analyzed the basis of the molecular heredity of related candidate genes in muscle development.A total of9 959 autosomal copy number variations(CNVs) were identified through selection signal analysis in 127 goat genomes.Specifically,we confirmed that the highest signal CNV(HSV) was a chromosomal arrangement containing an approximately 1.11 Mb(CHIR17:60062304-61171840 bp) duplicated fragment inserted in reverse orientation and a 5 362 bp deleted region(CHIR17:60145940-60151302 bp) with overlapping genes(e.g.,ARHGAP10,NR3C2,EDNRA,PRMT9,and TMEM184C).The homozygous duplicated HSV genotype(+/+) was found in 96% of Boer goats but was not detected in Eurasian goats and was only detected in 4% of indigenous African goats.The expression network of three candidate genes(ARHGAP10,NR3C2,and EDNRA)regulating dose transcription was constructed by RNA sequencing.Results indicated that these genes were involved in the proliferation and differentiation of skeletal muscle satellite cells(SMSCs) and their overexpression significantly increased the expression of SAA3.The HSV of the Boer goat contributed to superior skeletal muscle growth via the dose effects of overlapping genes.
基金supported by the State Key Program of National Natural Science Foundation of China(Grant No.12132003)State Key Laboratory of Explosion Science and Technology(Grant No.QNKT20-07)。
文摘The time-sequenced damage behavior of the reactive projectile impacting double-layer plates is discussed.The analytical model considering the combined effect of kinetic and chemical energy is developed to reveal the damage mechanism.The influences of impact velocity and reactive projectile chemical characteristics on the damage effect are decoupled analyzed based on this model.These analyses indicate that the high energy releasing efficiency and fast reaction propagation velocity of the reactive projectile are conducive to enhancing the damage effect.The experiments with various reactive projectiles impact velocity increasing from 702 to 1385 m/s were conducted to verify this model.The experimental results presented that,the damage hole radius of the rear-plate increases with the increase of impact velocity.At the impact velocity of 1350 m/s,the radius of damage hole formed by PTFE/Al/Bi_(2)O_(3),PTFE/Al/MoO_(3),PTFE/Al/Fe_(2)O_(3)projectile on the rear-plate become smaller in sequence.These results are consistent with the analytical model prediction,demonstrating that this model can predict the damage effect quantitatively.This work is of constructive significance to the application of reactive projectiles.
基金supported by the Provincial Key R&D Program of Zhejiang Province(Grant No.2021C03125)the Beijing Xisike Clinical Oncology Research Foundation(Grant No.Y-tongshu2021/ms-0003).
文摘Colorectal cancer(CRC)is the second most common cancer in China,the morbidity and mortality rates of which are rapidly increasing1,2.Among newly-diagnosed CRC patients,20%have metastatic disease at the time of presentation and an additional 25%present with localized disease and will subsequently develop metastases3.The treatment of metastatic colorectal cancer(mCRC)is gradually moving towards the era of precision therapy,which involves guided treatment based on individual genetic characteristics4.Since the first edition of the Chinese Society of Clinical Oncology(CSCO)guidelines was published in 2017,the guidelines have been updated annually according to the latest clinical trial findings5-9.Herein we summarize how the CSCO guidelines enable tailor-made treatments of mCRC with different molecular characteristics(Figure 1).
基金Supported by Grants from Key Projects in the National Science and Technology Pillar Program during the Twelfth Five-year Plan Period,No.2014BAI09B07grants from the National Natural Science Foundation of China,No.81101580 and No.81201640
文摘The colon is derived from the embryological midgut and hindgut separately,with the right colon and left colon having different features with regards to both anatomical and physiological characteristics.Cancers located in the right and left colon are referred to as right colon cancer(RCC) and left colon cancer(LCC),respectively,based on their apparent anatomical positions.Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC,but molecular features also vary between them,not to mention the distinguishing clinical manifestations.Disease-free survival after radical surgery of both RCC and LCC are similar.In the treatment of RCC,the benefit gained from adjuvant FOLFIRI chemotherapy is superior,or at least similar,to LCC,but inferior to LCC if FOLFOX regimen is applied.On the other hand,metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting.For KRAS wild-type cancers,LCC benefits more from cetuximab treatment than RCC.Moreover,advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC.Significant varieties exist at the molecular level between RCC and LCC,which may serve as the cause of all apparent differences.With respect to carcinogenesis mechanisms,RCC is associated with known gene types,such as MMR,KRAS,BRAF,and mi RNA-31,while LCC is associated with CIN,p53,NRAS,mi RNA-146 a,mi RNA-147 b,and mi RNA-1288.Regarding protein expression,RCC is related to GNAS,NQO1,telomerase activity,P-PDH,and annexin A10,while LCC is related to Topo I,TS,and EGFR.In addition,separated pathways dominate progressionto relapse in RCC and LCC.Therefore,RCC and LCC should be regarded as two heterogeneous entities,with this heterogeneity being used to stratify patients in order for them to have the optimal,current,and novel therapeutic strategies in clinical practice.Additional research is needed to uncover further differences between RCC and LCC.
基金Supported by The Grants from National Natural Science Foundation of China,No.81102013,No.81101580Zhejiang Provincial Natural Science Foundation of China,No.R2090353National High Technology Research and Development Program of China,No.2012AA02A506
文摘AIM:To develop a prognostic model to predict survival of patients with colorectal cancer (CRC). METHODS:Survival data of 837 CRC patients undergoing surgery between 1996 and 2006 were collected and analyzed by univariate analysis and Cox proportional hazard regression model to reveal the prognostic factors for CRC. All data were recorded using a standard data form and analyzed using SPSS version 18.0 (SPSS, Chicago, IL, United States). Survival curves were calculated by the Kaplan-Meier method. The log rank test was used to assess differences in survival. Univariate hazard ratios and significant and independent predictors of disease-specific survival and were identified by Cox proportional hazard analysis. The stepwise procedure was set to a threshold of 0.05. Statistical significance was defined asP < 0.05. RESULTS:The survival rate was 74% at 3 years and 68% at 5 years. The results of univariate analysis suggested age, preoperative obstruction, serum carcinoembryonic antigen level at diagnosis, status of resection, tumor size, histological grade, pathological type, lymphovascular invasion, invasion of adjacent organs, and tumor node metastasis (TNM) staging were positive prognostic factors (P < 0.05). Lymph node ratio (LNR) was also a strong prognostic factor in stage Ⅲ CRC (P < 0.0001). We divided 341 stage Ⅲ patients into three groups according to LNR values (LNR1, LNR ≤ 0.33, n = 211; LNR2, LNR 0.34-0.66, n = 76; and LNR3, LNR ≥ 0.67, n = 54). Univariate analysis showed a significant statistical difference in 3-year survival among these groups:LNR1, 73%; LNR2, 55%; and LNR3, 42% (P < 0.0001). The multivariate analysis results showed that histological grade, depth of bowel wall invasion, and number of metastatic lymph nodes were the most important prognostic factors for CRC if we did not consider the interaction of the TNM staging system (P < 0.05). When the TNM staging was taken into account, histological grade lost its statistical significance, while the specific TNM staging system showed a statistically significant difference (P < 0.0001). CONCLUSION:The overall survival of CRC patients has improved between 1996 and 2006. LNR is a powerful factor for estimating the survival of stage Ⅲ CRC patients.
基金Supported by The Department of Education of Zhejiang Province of China,grant No.Y200804314the Zhejiang Provincial Natural Science Foundation,grant No.R2090353+1 种基金the Department of Science and Technology of Zhejiang Province,grant No.2008C33039the Chinese Ministry of Health,grant No.N20100148
文摘AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients.
基金Supported by Grants from the Major State Basic Research Development Program of China, 973 Program No. 2004CB518707the Zhejiang Provincial Natural Science Foundation of China,No. R2090353the Fundamental Research Funds for the Central Universities, No. KYJD09007
文摘AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.
基金Supported by The National Natural Science Foundation of China, No. 81101580
文摘AIM: To evaluate the expression of special AT-rich sequence-binding protein 1 (SATB1 ) gene in colorectal cancer and its role in colorectal cancer cell proliferation and invasion.METHODS: Immunohistochemistry was used to detect the protein expression of SATB1 in 30 colorectal cancer (CRC) tissue samples and pair-matched adjacent nontumor samples. Cell growth was investigated after enhancing expression of SATB1. Wound-healing assay and Transwell assay were used to investigate the impact of SATB1 on migratory and invasive abilities of SW480 cells in vitro . Nude mice that received subcutaneous implantation or lateral tail vein were used to study the effects of SATB1 on tumor growth or metastasis in vivo . RESULTS: SATB1 was over-expressed in CRC tissues and CRC cell lines. SATB1 promotes cell proliferation and cell cycle progression in CRC SW480 cells. SATB1 over-expression could promote cell growth in vivo . In addition, SATB1 could significantly raise the ability of cell migration and invasion in vitro and promote the ability of tumor metastasis in vivo . SATB1 could up-regulate matrix metalloproteases 2, 9, cyclin D1 and vimentin, meanwhile SATB1 could down-regulate E-cadherin in CRC. CONCLUSION: SATB1 acts as a potential growth and metastasis promoter in CRC. SATB1 may be useful as a therapeutic target for CRC.
基金supported by the National Key R&D Program of China (No. 2018YFC1312100)the National Natural Science Foundation of China (No. 81872481)Traditional Chinese Medicine (Integrated Chinese and Western Medicine) Key Discipline Construction Project of Zhejiang Province (No. 2017-XK-A40)。
文摘Colorectal cancer(CRC) is one of the major cancers threatening life and health of Chinese residents. According to the latest data released by the National Cancer Center in2015(1), there were 387,000 new cases and 187,100 deaths of CRC in China, accounting for 9.87% and 8.01% of all malignancies. The first version of the Chinese Society of Clinical Oncology(CSCO) guidelines was released in April2017, and has been updated annually based on the latest clinical research data and the availability of new drugs(2-4). Here, we present the main updates of the 2021 version compared to 2020 version.
文摘The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.
基金supported by the National Natural Science Foundation of China(No.81872481)the Provincial Key R&D Program of Zhejiang Province(No.2021C03125)。
文摘Colorectal cancer(CRC) is the third most common cancer worldwide and the second most common in tumor-related mortality by Global Cancer Statistics 2020(1). Recent data show that the incidence and mortality of CRC in China are increasing(2-4), with the number of new cases and deaths reaching 607,900 and 261,777 in 2019.
基金supported by grants from the National Natural Science Foundation of China(NSFC)(No.#81072148,#81071634and#30928012)Natural Science Foundation of Chongqing(No.2010BB5101)Shenzhen Science Fund for Distinguished Young Scholars(No.JC201005270328A)
文摘Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes(TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.