Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conve...Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conversion of embryos to plants.The purpose of this study was to establish a regeneration system via somatic embryogenesis from immature embryos explants in‘Heiye'cultivar of litchi.Our results demonstrated that MS medium supplemented with 2.0 mg L^(-1)2,4-D was optimal for callus induction.For somatic embryo(SE)induction,MS medium containing0.5 g L^(-1) activated charcoal(AC)was the most effective,while the use of zeatin(ZT)and thidiazuron(TDZ)resulted in abnormal somatic embryos.The rooting and regeneration rate of 2.15%and 17.5%,respectively,were achieved using MS medium supplemented with 0.5 g L^(-1) AC.Furthermore,transcriptome analysis was performed on embryogenic callus(EC),globular embryo(GE),and heart embryo(HE)to explore the molecular mechanisms of early somatic embryogenesis.2,587 common differentially expressed genes(DEGs)between EC_vs_GE and EC_vs_HE were identified,and the expression patterns of these common DEGs were separated into twelve major clusters.GO annotation and KEGG pathway analysis revealed that these common DEGs were implicated in plant hormone signal transduction,auxin-activated signaling pathway,and other biological processes.Additionally,differentially expressed transcription factors were identified,and the function of LcBBM2 which is specifically highly expressed during early somatic embryogenesis was verified.Overexpression of LcBBM2 in tomato promotes callus and shoot formation.Therefore,this study can provide a theoretical basis and technical support for genetic breeding improvement of litchi.展开更多
BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma me...BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.展开更多
Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early de...Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early detection of recurrence,significantly improving patient outcomes.However,intensive surveillance strategies have shown mixed results compared to less intensive methods,emphasizing the necessity for personalized,risk-adapted approaches.The observed suboptimal adherence to existing surveillance protocols underscores the urgent need for more tailored and efficient strategies.In this context,circulating tumor DNA(ctDNA)emerges as a promising biomarker with significant potential to revolutionize post-treatment surveillance,demonstrating high specificity[0.95,95%confidence interval(CI):0.91-0.97]and robust diagnostic odds(37.6,95%CI:20.8-68.0)for recurrence detection.Furthermore,artificial intelligence and machine learning models integrating patient-specific and tumor features can enhance risk stratification and optimize surveillance strategies.The reported area under the receiver operating characteristic curve,measuring artificial intelligence model performance in predicting CRC recurrence,ranged from 0.581 and 0.593 at the lowest to 0.979 and 0.978 at the highest in training and validation cohorts,respectively.Despite this promise,addressing cost,accessibility,and extensive validation remains crucial for equitable integration into clinical practice.展开更多
BACKGROUND With the growing scholarly and clinical fascination with somatic symptom dis-order(SSD),a bibliometric analysis is lacking.AIM To conduct a bibliometric analysis to investigate the current status and fronti...BACKGROUND With the growing scholarly and clinical fascination with somatic symptom dis-order(SSD),a bibliometric analysis is lacking.AIM To conduct a bibliometric analysis to investigate the current status and frontiers of SSD.METHODS The documents related to SSD are obtained from the web of science core collection database(WoSCC),and VOSviewer 1.6.16 from January 1,2000 to December 31,2023,and the WoSCC’s literature analysis wire were used to conduct the biblio-metric analysis.RESULTS A total of 567 documents related to SSD were included,and 2325 authors across 947 institutions from 57 countries/regions have contributed to SSD research,published in 277 journals.The most productive author,institution,country and journal were Löwe B,University of Hamburg,Germany,and Journal of Psycho-somatic Research respectively.The first high-cited document was published in the Journal of Psychosomatic Research in 2013 by Dimsdale JE and colleagues,which explored the rationale behind the SSD diagnosis introduction in diagnostic and statistical manual of mental disorders.CONCLUSION In conclusion,the main research hotspots and frontiers in the field of SSD are validity and reliability of the SSD criteria,functional impairment of SSD,and the treatment for SSD.More high-quality studies are needed to assess the diagnosis and treatment of SSD.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor ...Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.展开更多
Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untr...Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untranslated regions(3'UTRs)on alternative polyadenylation(APA)of m RNA remains lacking.In this study,we analyze 10,199 tumor samples across 32 cancer types and identify 1333 somatic single nucleotide variants(SNVs)associated with abnormal 3'UTR APA.Mechanistically,these 3'UTR SNVs can alter cisregulatory elements,such as the poly(A)signal and UGUA motif,leading to changes in APA.Minigene assays confirm that 3'UTR SNVs in multiple genes,including RPS23 and CHTOP,induce aberrant APA.Among affected genes,62 exhibit differential stability between tandem 3'UTR isoforms,including HSPA4and UCK2,validated by experimental assays.Finally,we establish that SNV-related abnormal APA usage serves as an additional layer of expression regulation for tumor-suppressor gene HMGN2 in breast cancer.Collectively,this study reveals 3'UTR APA as a critical mechanism mediating the functional impact of somatic noncoding variants in human cancers.展开更多
Litchi has great economic significance as a global fruit crop.However,the advancement of litchi functional genomics has encountered substantial obstacles due to its recalcitrance to stable transformation.Here,we prese...Litchi has great economic significance as a global fruit crop.However,the advancement of litchi functional genomics has encountered substantial obstacles due to its recalcitrance to stable transformation.Here,we present an efficacious Agrobacterium tumefaciens-mediated transformation system in somatic embryos of‘Heiye'litchi.This system was developed through the optimization of key variables encompassing explant selection,A.tumefaciens strain delineation,bacterium concentration,infection duration,and infection methodology.The subsequent validation of the transformation technique in litchi was realized through the ectopic expression of LcMYB1,resulting in the generation of transgenic calli.However,the differentiation of transgenic calli into somatic embryos encountered substantial challenges.To delineate the intricate molecular underpinnings of LcMYB1's inhibitory role in somatic embryo induction,a comprehensive transcriptome analysis was conducted that encompassed embryogenic calli(C),globular embryos(G),and transgenic calli(TC).A total of 1,166 common differentially expressed genes(DEGs)were identified between C-vs.-G and C-vs.-TC.Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that these common DEGs were mostly related to plant hormone signal transduction pathways.Furthermore,RT-qPCR corroborated the pronounced down-regulation of numerous genes that are associated with somatic embryo induction within the transgenic calli.The development of this transformation system provides valuable support for functional genomics research in litchi.展开更多
Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exite...Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exited into peripheral blood as a result of the dynamic interactions between the bone marrow(BM)microenvironment and neoplastic plasma cells.Chemokine receptors like chemokine receptor 4(CXCR4)and integrins are known to play a role in homing and migration of plasma cells(PCs).The hypoxic microenvironment in the BM niche also contributes to their circulation through various mechanisms.In addition,the CCL3–CCR1 axis probably competes with the retention signals from the CXCR4–α4β1(VLA-4)interaction and actively promotes the exit of PCs from the BM.CTPCs,even in extremely low numbers,can be detected and quantified by high-sensitivity techniques like multi-color flow cytometry and next-generation sequencing.High load of CTPCs noted in patients of plasma cell neoplasm;monoclonal gammopathy of undetermined significance(MGUS),smoldering multiple myeloma(SMM),multiple myeloma(MM)is a strong predictor of shorter progression free survival(PFS)as well as overall survival(OS).In newly diagnosed patients of MM,a load of CTPCs correlates with the outcomes,i.e.,OS and PFS.With more studies collaborating on the results of previous reports,assessment of the burden of CTPCs may become a complimentary approach for non-invasive risk stratification of MM patients and evaluating the response to therapy.Future research on larger cohorts and longer follow-ups may help to improve the existing staging system by incorporating the load of CTPCs as one of the prognostic indicators.Further studies based on isolation and genetic characterization of CTPCs may help in understanding the pathophysiology of the progression of the disease and may open avenues for newer treatment modalities.This review discusses the pathobiological aspects leading to circulation of neoplastic/tumor plasma cells in peripheral blood and provides a summary of research work done in last two decades on its prognostic importance in various plasma cells neoplasms.展开更多
Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agem...Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agement of solid tumor patients and to evaluate the quality of the current studies.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched to collect cohort studies on ctDNA in the prognosis of solid tumor patients from January 2016 to May 2022.The language was limited to English.Information including general information,participants and cancer characteristics,ctDNA and outcome information were extracted.The quality of the studies was assessed using the Newcastle-Ottawa Scale checklist.Results:A total of 214 studies were included in the final analysis,encompassing 21,076 patients.The number of studies has increased annually from 2016 to 2022.The most common types of solid tumors studied were colorectal cancer(27.10%),lung cancer(20.09%),pancreatic cancer(16.82%),and breast cancer(14.02%).The top three journals by number of publications had an impact factor in 2023 greater than 10.Of the studies,the median sample size was 69(interquartile range:41-111),69.81%had a sample size<100,68.92%had a median/mean age≥60 years,and 74.05%were from developed countries.Multi-center studies accounted for 40.36%.Additionally,29.82%of the studies had a bias risk score≤6.Only 16.67%of studies on liver cancer had a bias risk score>6.The primary criteria not met by the studies included“Adequacy of follow-up of cohorts”(33.33%),“Assessment of outcome”(32.16%)and“Representativeness of the exposed cohort”(27.49%).Conclusions:The prognostic value of ctDNA in patients with solid tumors is gaining increasing attention,leading to a steady rise in the number of studies.However,many studies still suffer from small sample sizes and a lack of representativeness.Furthermore,details regarding ctDNA detection methods and results reporting are often insufficiently described.There is an urgent need to improve the quality of such research.展开更多
As a pyrometallurgical process,circulating fluidized bed(CFB) roasting has good potential for application in desulfurization of high-sulfur bauxite.The gas-solid distribution and reaction during CFB roasting of high-s...As a pyrometallurgical process,circulating fluidized bed(CFB) roasting has good potential for application in desulfurization of high-sulfur bauxite.The gas-solid distribution and reaction during CFB roasting of high-sulfur bauxite were simulated using the computational particle fluid dynamics(CPFD) method.The effect of primary air flow velocity on particle velocity,particle volume distribution,furnace temperature distribution and pressure distribution were investigated.Under the condition of the same total flow of natural gas,the impact of the number of inlets on the desulfurization efficiency,atmosphere mass fraction distribution and temperature distribution in the furnace was further investigated.展开更多
Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and ...Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.展开更多
Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to sys...Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov database was searched from January 2016 to April 2023.Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included.Pooled hazard risk ratios(HRs)were calculated for the primary outcomes,relapse-free survival(RFS),and overall survival(OS).Random-effects models were preferred considering the potential heterogeneity.Results:Sixty-five cohort studies were included.Association between ctDNA and shorter RFS or OS was significant,especially after the full-course treatment recommended by the guidelines(HR=8.92[95%CI:6.02-13.22],P<0.001,I^(2)=73%;HR=3.05[95%CI:1.72-5.41],P<0.001,I^(2)=48%)for all types of CRC patients.Despite the presence of heterogeneity,subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause.Besides,ctDNA may detect recurrence earlier than radiographic progression,but no uniform sampling time point between studies might bring bias.However,ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer.Conclusion:ctDNA detection was significantly associated with poorer prognosis.The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.展开更多
The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
In oil and gas well cementing processes,accurately predicting the bottom hole circulating temperature(BHCT)is critical to ensuring effective zonal isolation.Overestimating the temperature can lead to excessive retarda...In oil and gas well cementing processes,accurately predicting the bottom hole circulating temperature(BHCT)is critical to ensuring effective zonal isolation.Overestimating the temperature can lead to excessive retardation issues,while underestimation can cause cementing accidents.Current methods for calculating the BHCT of cement slurry typically simplify the cementing processes to a single-fluid circulation and ignore the impact of pre-cementing processes on temperature,leading to significant discrepancies between calculated and actual results.In this study,the wellbore and formation are simplified into a two-dimensional axisymmetric structure,and a mathematical model of the temperature field under multi-fluid and multi-step conditions is established based on the law of energy conservation.The finite volume method was used to discretize the model,and a transient temperature field solver for the entire cementing process was developed,which can numerically calculate the temperature of any fluid at any time,any location.For an actual well example,the temperature distribution of the wellbore and formation after casing running is taken as the initial condition.Numerical calculations were performed sequentially to calculate the temperature fields of circulation flushing,wellbore preparation,and cementing,as well as the BHCT of the cement slurry.The study reveals that during the circulation flushing stage,the maximum temperature point in the wellbore is located at a distance of about 366 m above the bottom of the well.In the wellbore preparation stage,due to static heat exchange,the maximum temperature point gradually shifts to the bottom of the well.The BHCT of cement slurry changes continuously under cementing processes with multi-fluid and multi-step,making it a transient value.The BHCT of the lead slurry and tail slurry are not equal,with the maximum BHCT of the tail slurry being 2.46°C higher than that of the lead slurry.If circulation flushing and wellbore preparation are not considered,the calculated BHCT of the cement slurry will have errors of+6.8%and-1.9%.The study highlighted that considering thermal effects of all cementing stages,such as circulation flushing and wellbore preparation,in BHCT calculations can help improve prediction accuracy.展开更多
BACKGROUND Circulating tumor cells(CTCs)are crucial for improving our knowledge regarding tumor progress,prognosis,and recurrence possibility.AIM To evaluate the role of CTCs in the early diagnosis and treatment of ga...BACKGROUND Circulating tumor cells(CTCs)are crucial for improving our knowledge regarding tumor progress,prognosis,and recurrence possibility.AIM To evaluate the role of CTCs in the early diagnosis and treatment of gastric cancer.METHODS From June 2020 to December 2021,a randomized study was conducted in our institution involving 80 patients scheduled for surgery for gastric cancer.The patients were divided into two groups:A control group that was tested for traditional serum markers and a study group that was assessed for serum CTCs.RESULTS In the study cohort,CTC levels did not correlate significantly with patient age,gender,or degree of tumor differentiation(P>0.05).However,there was a significant correlation with the tumor-node-metastasis stage of the tumor(P<0.05).In the study group,the CTC diagnostic positivity rate was 62.50%(25 out of 40 patients),while the positivity rate for conventional serum markers in the control group was 47.50%(19 out of 40 patients).The positive detection rate in the study group was significantly higher than that of the control group(P<0.05).CONCLUSION CTCs have slight invasion and high sensitivity and specificity,presenting great value for early clinical diagnosis of recurrence and metastasis.It will improve the deceleration of disease development and increase the survival rate.展开更多
BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need...BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.展开更多
AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to ex...AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to explore the causal relationships between 91 CIPs and various severities of DR:background DR(BDR)or non-proliferative DR(NPDR),and proliferative DR(PDR).Single-nucleotide polymorphisms(SNPs)related to the 91 CIPs as exposure factors were identified.These SNPs were selected from an extensive genome-wide association study(GWAS)analyzing large genomic datasets.Genetic variation data of various DR phenotypes provided by the FinnGen collaboration were utilized as outcomes.Inverse-variance weighting(IVW)was used as the main MR analysis.Robustness of study results was evaluated through a series of sensitivity analyses,employing the MR-pleiotropy-test and mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)to confirm the absence of pleiotropy.RESULTS:In a bidirectional MR analysis,we uncovered a complex relationship between CIPs and DR.Elevated levels of tumor necrosis factor ligand superfamily member 14(TNFSF14),latency associated peptide transforming growth factors beta-1(LAP-TGF-beta1),interleukin-10(IL-10),and vascular endothelial growth factor A(VEGF-A)were associated with a reduced risk of NPDR.Conversely,elevated levels of fibroblast growth factor 23(FGF-23)were associated with an increased risk of NPDR.Concentrations of adenosine deaminase(ADA),matrix metalloproteinase-10(MMP-10),eotaxin,and IL-10 showed elevated levels and were linked to a reduced risk of NPDR.On the other hand,the levels of oncostatin-M,beta-nerve growth factor(β-NGF),and interleukin-7(IL-7)were elevated and associated with an increased risk of SNPDR.Elevated levels of ADA,MMP-10,and macrophage colony-stimulating factor 1(CSF1)were linked to a lower likelihood of PDR.Conversely,elevated levels of Caspase 8 and glial cell line-derived neurotrophic factor(GDNF)were associated with an increased risk of PDR.In reverse MR analysis,DR affected the expression of these factors.CONCLUSION:Our research demonstrates evidence supporting a potential causal link between key inflammatory factors and the risk and prognosis of various DR phenotypes.These findings emphasize the regulation of inflammatory factors responses as a strategic approach for preventing and managing DR.Altogether,our results validate the pathogenic role of inflammatory factors dysregulation in DR and support the rationale for exploring immunotherapeutic targets further.展开更多
The development of renewable energy power generation for carbon neutrality and energy transition has been increasing worldwide,leading to an increasing demand for high-power conversion.Compared with traditional interl...The development of renewable energy power generation for carbon neutrality and energy transition has been increasing worldwide,leading to an increasing demand for high-power conversion.Compared with traditional interleaved paralleling,the integrated paralleling of three-level inverters can further reduce the output harmonics.Moreover,a well-designed switching sequence ensures that the average circulating current is zero,which provides a superior and feasible solution to satisfy the demands of high-power operations.However,a large instantaneous loop current exists between shunt converters,which leads to disadvantages such as higher switching device stress and loss.In this study,by utilizing the state-distribution redundancy provided by the integrated modulation process,a new design for switch-ing sequences is suggested for the integrated modulation of shunt three-level converters.This design aims to reduce the circulating current while better preserving the same output current harmonics than traditional parallel methods.The proposal includes an in-depth analysis and explanation of the implementation process.Finally,the proposed method is validated through simulations and prototype experi-ments.The results indicate that compared with traditional methods,the adoption of the improved switching sequence presented in this study leads to an average reduction of 3.2%in the total harmonic distortion of the inverter’s output and an average decrease of 32%in the amplitude of the circulating current.Both the output harmonics and circulating currents are significantly suppressed across various modulation indices.展开更多
BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery....BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery.Occult metastases(OMs)must be accurately predicted to optimize multidisciplinary treatment.AIM To investigate the efficacy of circulating tumor DNA(ctDNA)in predicting OM.METHODS Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.RESULTS Among 135 PDAC patients,38 had OM and 35 were positive for ctDNA.The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM.ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients.Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.CONCLUSION Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.展开更多
基金supported by the National Natural Science Fund of China(Grant Nos.31872066 and 32272663)the Science and Technology Planning Project of Guangzhou(Grant No.2023B01J2002)+1 种基金the Key Research and Development Program of Hainan(Grant No.ZDYF2023XDNY052)the Seed Industry Engineering Project of Ministry of Agriculture and Rural Affairs of Guangdong(Grant Nos.2022-NPY-00-004 and 2022-NBH-00-001)。
文摘Litchi chinensis Sonn.is an important economic fruit tree in tropical and subtropical regions.Regrettably,the efficiency of plant regeneration via somatic embryogenesis in litchi is typically low due to the poor conversion of embryos to plants.The purpose of this study was to establish a regeneration system via somatic embryogenesis from immature embryos explants in‘Heiye'cultivar of litchi.Our results demonstrated that MS medium supplemented with 2.0 mg L^(-1)2,4-D was optimal for callus induction.For somatic embryo(SE)induction,MS medium containing0.5 g L^(-1) activated charcoal(AC)was the most effective,while the use of zeatin(ZT)and thidiazuron(TDZ)resulted in abnormal somatic embryos.The rooting and regeneration rate of 2.15%and 17.5%,respectively,were achieved using MS medium supplemented with 0.5 g L^(-1) AC.Furthermore,transcriptome analysis was performed on embryogenic callus(EC),globular embryo(GE),and heart embryo(HE)to explore the molecular mechanisms of early somatic embryogenesis.2,587 common differentially expressed genes(DEGs)between EC_vs_GE and EC_vs_HE were identified,and the expression patterns of these common DEGs were separated into twelve major clusters.GO annotation and KEGG pathway analysis revealed that these common DEGs were implicated in plant hormone signal transduction,auxin-activated signaling pathway,and other biological processes.Additionally,differentially expressed transcription factors were identified,and the function of LcBBM2 which is specifically highly expressed during early somatic embryogenesis was verified.Overexpression of LcBBM2 in tomato promotes callus and shoot formation.Therefore,this study can provide a theoretical basis and technical support for genetic breeding improvement of litchi.
基金Supported by the Medical Talents of Wuhan Health and Family Planning Commission,No.2017[51](to Yu J)the Medical Talents of Wuhan Hospital of Traditional Chinese and Western Medicine(to Yu J)+1 种基金the Hubei Natural Science Foundation,No.2023AFB1091Wuhan Medical Research Project,No.WX23A36(to Yu J).
文摘BACKGROUND Cholangiocarcinoma(CCA),also known as bile duct cancer,is a devastating malignancy primarily affecting the biliary tract.AIM To assess their performance in clinical diagnosis and monitoring of CCA,plasma methylation and circulating tumor cells were detected.METHODS Plasma samples were collected from Hubei Cancer Hospital(n=156).Plasma DNA was tested to detect SHOX2,HOXA9,SEPTIN9,and RASSF1A methylation using TaqMan PCR.Circulating tumor cells(CTCs)were detected in the peripheral blood of patients using the United States Food and Drug Administration-approved cell search system before and after clinical therapy.The CCA diagnostic value was estimated using the area under the curve.The independent prognosis risk factors for patients with CCA were estimated using Cox and logistic regression analyses.RESULTS The sensitivity and specificity of the four DNA plasma methylations exhibited 64.74%sensitivity and 93.88%specificity for detecting CCA.The receiver operating characteristic curve of the combined value for CCA diagnosis in plasma was 0.828±0.032.RASSF1A plasma methylation was related to the prognosis of patients with CCA.We determined the prognostic hazard ratio for CCA using CTC count,tumor stage,methylation,and carbohydrate antigen 19-9 levels as key factors.Our overall survival nomogram achieved a C-index of 0.705(0.605-0.805).CONCLUSION SHOX2,HOXA9,SEPTIN9,and RASSF1A plasma methylation demonstrated increased sensitivity for diagnosing CCA.RASSF1A plasma methylation and CTCs were valuable predictors to assess CCA prognosis and recurrence.
文摘Given the growing burden of colorectal cancer(CRC)as a global health challenge,it becomes imperative to focus on strategies that can mitigate its impact.Posttreatment surveillance has emerged as essential for early detection of recurrence,significantly improving patient outcomes.However,intensive surveillance strategies have shown mixed results compared to less intensive methods,emphasizing the necessity for personalized,risk-adapted approaches.The observed suboptimal adherence to existing surveillance protocols underscores the urgent need for more tailored and efficient strategies.In this context,circulating tumor DNA(ctDNA)emerges as a promising biomarker with significant potential to revolutionize post-treatment surveillance,demonstrating high specificity[0.95,95%confidence interval(CI):0.91-0.97]and robust diagnostic odds(37.6,95%CI:20.8-68.0)for recurrence detection.Furthermore,artificial intelligence and machine learning models integrating patient-specific and tumor features can enhance risk stratification and optimize surveillance strategies.The reported area under the receiver operating characteristic curve,measuring artificial intelligence model performance in predicting CRC recurrence,ranged from 0.581 and 0.593 at the lowest to 0.979 and 0.978 at the highest in training and validation cohorts,respectively.Despite this promise,addressing cost,accessibility,and extensive validation remains crucial for equitable integration into clinical practice.
文摘BACKGROUND With the growing scholarly and clinical fascination with somatic symptom dis-order(SSD),a bibliometric analysis is lacking.AIM To conduct a bibliometric analysis to investigate the current status and frontiers of SSD.METHODS The documents related to SSD are obtained from the web of science core collection database(WoSCC),and VOSviewer 1.6.16 from January 1,2000 to December 31,2023,and the WoSCC’s literature analysis wire were used to conduct the biblio-metric analysis.RESULTS A total of 567 documents related to SSD were included,and 2325 authors across 947 institutions from 57 countries/regions have contributed to SSD research,published in 277 journals.The most productive author,institution,country and journal were Löwe B,University of Hamburg,Germany,and Journal of Psycho-somatic Research respectively.The first high-cited document was published in the Journal of Psychosomatic Research in 2013 by Dimsdale JE and colleagues,which explored the rationale behind the SSD diagnosis introduction in diagnostic and statistical manual of mental disorders.CONCLUSION In conclusion,the main research hotspots and frontiers in the field of SSD are validity and reliability of the SSD criteria,functional impairment of SSD,and the treatment for SSD.More high-quality studies are needed to assess the diagnosis and treatment of SSD.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
文摘Molecular profiling of biliary tract cancers(BTCs)has paved the way for a broader range of therapeutic options,leading to improved survival outcomes.Given the challenges of tissue evaluation in BTCs,circulating tumor DNA(ct-DNA)has emerged as a promising non-invasive biomarker for genomic profiling.Bile has been proven to be a reliable ctDNA source,demonstrating higher concordance with tumor tissue than plasma.More importantly,ctDNA provides valuable insights into both clonal evolution and treatment response,including the detection of resistance mechanisms and mutation clearance,which are often associated with disease control.Although its role in recurrence monitoring remains investigational,early studies suggest that ctDNA detection may precede radiological recurrences.This review examines recent advancements in ctDNA analysis for patients with BTC,highlighting key developments,current clinical implications,and ongoing challenges.Large-scale prospective studies are needed to validate the clinical utility of ctDNA and to support its integration into BTC management.
基金financially supported by the National Key R&D Program of China(2023YFC3603300,2021YFA0909300)National Natural Science Foundation of China(92249302,32370592,32400437)China Postdoctoral Science Foundation(BX20230073 and 2023M740709)。
文摘Somatic variants in the cancer genome influence gene expression through diverse mechanisms depending on their specific locations.However,a systematic evaluation of the effects of somatic variants located in 3'untranslated regions(3'UTRs)on alternative polyadenylation(APA)of m RNA remains lacking.In this study,we analyze 10,199 tumor samples across 32 cancer types and identify 1333 somatic single nucleotide variants(SNVs)associated with abnormal 3'UTR APA.Mechanistically,these 3'UTR SNVs can alter cisregulatory elements,such as the poly(A)signal and UGUA motif,leading to changes in APA.Minigene assays confirm that 3'UTR SNVs in multiple genes,including RPS23 and CHTOP,induce aberrant APA.Among affected genes,62 exhibit differential stability between tandem 3'UTR isoforms,including HSPA4and UCK2,validated by experimental assays.Finally,we establish that SNV-related abnormal APA usage serves as an additional layer of expression regulation for tumor-suppressor gene HMGN2 in breast cancer.Collectively,this study reveals 3'UTR APA as a critical mechanism mediating the functional impact of somatic noncoding variants in human cancers.
基金supported by the National Natural Science Foundation of China(31872066 and 32272663)the Science and Technology Planning Project of Guangzhou,China(2023B01J2002)+2 种基金the Key Research and Development Program of Hainan,China(ZDYF2023XDNY052)the Seed Industry Engineering Project of Department of Agriculture and Rural Affairs of Guangdong,China(2022-NPY-00-004 and 2022-NBH00-001)the Litchi Industry Science and Technology Special Mission of Yunnan,China(202204BI090021)。
文摘Litchi has great economic significance as a global fruit crop.However,the advancement of litchi functional genomics has encountered substantial obstacles due to its recalcitrance to stable transformation.Here,we present an efficacious Agrobacterium tumefaciens-mediated transformation system in somatic embryos of‘Heiye'litchi.This system was developed through the optimization of key variables encompassing explant selection,A.tumefaciens strain delineation,bacterium concentration,infection duration,and infection methodology.The subsequent validation of the transformation technique in litchi was realized through the ectopic expression of LcMYB1,resulting in the generation of transgenic calli.However,the differentiation of transgenic calli into somatic embryos encountered substantial challenges.To delineate the intricate molecular underpinnings of LcMYB1's inhibitory role in somatic embryo induction,a comprehensive transcriptome analysis was conducted that encompassed embryogenic calli(C),globular embryos(G),and transgenic calli(TC).A total of 1,166 common differentially expressed genes(DEGs)were identified between C-vs.-G and C-vs.-TC.Gene Ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that these common DEGs were mostly related to plant hormone signal transduction pathways.Furthermore,RT-qPCR corroborated the pronounced down-regulation of numerous genes that are associated with somatic embryo induction within the transgenic calli.The development of this transformation system provides valuable support for functional genomics research in litchi.
文摘Circulating plasma cells(CPCs)in patients of plasma cell neoplasm have been an area of intense research in recent decades.Circulating tumor plasma cells(CTPCs)might represent a sub-clone of tumor cells that have exited into peripheral blood as a result of the dynamic interactions between the bone marrow(BM)microenvironment and neoplastic plasma cells.Chemokine receptors like chemokine receptor 4(CXCR4)and integrins are known to play a role in homing and migration of plasma cells(PCs).The hypoxic microenvironment in the BM niche also contributes to their circulation through various mechanisms.In addition,the CCL3–CCR1 axis probably competes with the retention signals from the CXCR4–α4β1(VLA-4)interaction and actively promotes the exit of PCs from the BM.CTPCs,even in extremely low numbers,can be detected and quantified by high-sensitivity techniques like multi-color flow cytometry and next-generation sequencing.High load of CTPCs noted in patients of plasma cell neoplasm;monoclonal gammopathy of undetermined significance(MGUS),smoldering multiple myeloma(SMM),multiple myeloma(MM)is a strong predictor of shorter progression free survival(PFS)as well as overall survival(OS).In newly diagnosed patients of MM,a load of CTPCs correlates with the outcomes,i.e.,OS and PFS.With more studies collaborating on the results of previous reports,assessment of the burden of CTPCs may become a complimentary approach for non-invasive risk stratification of MM patients and evaluating the response to therapy.Future research on larger cohorts and longer follow-ups may help to improve the existing staging system by incorporating the load of CTPCs as one of the prognostic indicators.Further studies based on isolation and genetic characterization of CTPCs may help in understanding the pathophysiology of the progression of the disease and may open avenues for newer treatment modalities.This review discusses the pathobiological aspects leading to circulation of neoplastic/tumor plasma cells in peripheral blood and provides a summary of research work done in last two decades on its prognostic importance in various plasma cells neoplasms.
基金funded by the National Natural Science Foundation of China(grant numbers:72474008,72074011)the Capital’s Funds for Health Improvement and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2).
文摘Objective:Circulating tumor DNA(ctDNA)has shown potential as a prognostic biomarker in patients with solid tumors.This study aimed to systematically summarize the global application of ctDNA in the prognostic man-agement of solid tumor patients and to evaluate the quality of the current studies.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched to collect cohort studies on ctDNA in the prognosis of solid tumor patients from January 2016 to May 2022.The language was limited to English.Information including general information,participants and cancer characteristics,ctDNA and outcome information were extracted.The quality of the studies was assessed using the Newcastle-Ottawa Scale checklist.Results:A total of 214 studies were included in the final analysis,encompassing 21,076 patients.The number of studies has increased annually from 2016 to 2022.The most common types of solid tumors studied were colorectal cancer(27.10%),lung cancer(20.09%),pancreatic cancer(16.82%),and breast cancer(14.02%).The top three journals by number of publications had an impact factor in 2023 greater than 10.Of the studies,the median sample size was 69(interquartile range:41-111),69.81%had a sample size<100,68.92%had a median/mean age≥60 years,and 74.05%were from developed countries.Multi-center studies accounted for 40.36%.Additionally,29.82%of the studies had a bias risk score≤6.Only 16.67%of studies on liver cancer had a bias risk score>6.The primary criteria not met by the studies included“Adequacy of follow-up of cohorts”(33.33%),“Assessment of outcome”(32.16%)and“Representativeness of the exposed cohort”(27.49%).Conclusions:The prognostic value of ctDNA in patients with solid tumors is gaining increasing attention,leading to a steady rise in the number of studies.However,many studies still suffer from small sample sizes and a lack of representativeness.Furthermore,details regarding ctDNA detection methods and results reporting are often insufficiently described.There is an urgent need to improve the quality of such research.
基金supported by the National Key Research and Development Program of China(2022YFC2904400)Guangxi Science and Technology Major Project(Gui Ke AA23023033)。
文摘As a pyrometallurgical process,circulating fluidized bed(CFB) roasting has good potential for application in desulfurization of high-sulfur bauxite.The gas-solid distribution and reaction during CFB roasting of high-sulfur bauxite were simulated using the computational particle fluid dynamics(CPFD) method.The effect of primary air flow velocity on particle velocity,particle volume distribution,furnace temperature distribution and pressure distribution were investigated.Under the condition of the same total flow of natural gas,the impact of the number of inlets on the desulfurization efficiency,atmosphere mass fraction distribution and temperature distribution in the furnace was further investigated.
文摘Circulating tumor DNA(ctDNA)is the free DNA released by tumor or circulating tumor cells,which is associated with many tumor characteristics and can be used as a biomarker for early screening,monitoring,prognosis,and prediction of therapeutic response in patients with cancer.The field of gastric cancer is very attractive because there are no high-quality screening,monitoring,or prediction methods.Gastric cancer is characterized by great tumor heterogeneity,great differences in genetic and epigenetic characteristics among different subgroups of gastric cancer,and high sensitivity and specificity of methylated ctDNA,which is conducive to the identification of tumor genotypes and the formulation of accurate diagnostic and treatment strategies.In addition,many studies have confirmed that methylated DNA has unique advantages in predicting treatment response,adjuvant therapy,and drug resistance and can be used to increase the efficacy of chemotherapy regimens,improve the chemotherapy response of patients in the future,and even treat multidrug resistance.However,methylated ctDNA also faces many problems,such as low sensitivity and specificity in a single target,limited association between some gastric cancer subtypes and ctDNA,risk of off-target effects,and lack of large-sample and high-quality clinical research evidence.This review mainly summarizes the current research on the DNA methylation of circulating gastric cancer tumors and links these findings with the early screening of gastric cancer,recurrence monitoring,and potential treatment opportunities.With the advancement of technology and the deepening of cross-research between doctors and professionals,ctDNA detection will reveal more disease information and become an important basis for the field of gastric cancer and precision medicine treatment.
基金funded by the Capital’s Funds for Health Improve-ment and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2)National Natural Science Foundation of China(grant number:72474008).
文摘Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential biomarker in colorectal cancer(CRC)patients.However,the role of ctDNA in CRC prognosis prediction remains unclear.The objective is to systematically assess the clinical value of ctDNA in colorectal cancer prognosis prediction throughout the treatment cycle.Methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov database was searched from January 2016 to April 2023.Observational studies and randomized clinical trials reporting on ctDNA and prognostic outcomes in CRC patients were included.Pooled hazard risk ratios(HRs)were calculated for the primary outcomes,relapse-free survival(RFS),and overall survival(OS).Random-effects models were preferred considering the potential heterogeneity.Results:Sixty-five cohort studies were included.Association between ctDNA and shorter RFS or OS was significant,especially after the full-course treatment recommended by the guidelines(HR=8.92[95%CI:6.02-13.22],P<0.001,I^(2)=73%;HR=3.05[95%CI:1.72-5.41],P<0.001,I^(2)=48%)for all types of CRC patients.Despite the presence of heterogeneity,subgroup analyses showed that the cancer type and ctDNA detection assays may be the underlying cause.Besides,ctDNA may detect recurrence earlier than radiographic progression,but no uniform sampling time point between studies might bring bias.However,ctDNA detection did not appear to correlate with pathological complete response achievement in patients with locally advanced rectal cancer.Conclusion:ctDNA detection was significantly associated with poorer prognosis.The potential applications in prognostic prediction are promising and remain to be evaluated in other fields.
文摘The somatotopic representation of specific body parts is a well-established spatial organizational principle in the primary somatosensory and motor cortices.
基金supported by the National Natural Science Foundation of China(No.U22B6003 and No.52274010)the China Scholarship Council(No.202008080235)。
文摘In oil and gas well cementing processes,accurately predicting the bottom hole circulating temperature(BHCT)is critical to ensuring effective zonal isolation.Overestimating the temperature can lead to excessive retardation issues,while underestimation can cause cementing accidents.Current methods for calculating the BHCT of cement slurry typically simplify the cementing processes to a single-fluid circulation and ignore the impact of pre-cementing processes on temperature,leading to significant discrepancies between calculated and actual results.In this study,the wellbore and formation are simplified into a two-dimensional axisymmetric structure,and a mathematical model of the temperature field under multi-fluid and multi-step conditions is established based on the law of energy conservation.The finite volume method was used to discretize the model,and a transient temperature field solver for the entire cementing process was developed,which can numerically calculate the temperature of any fluid at any time,any location.For an actual well example,the temperature distribution of the wellbore and formation after casing running is taken as the initial condition.Numerical calculations were performed sequentially to calculate the temperature fields of circulation flushing,wellbore preparation,and cementing,as well as the BHCT of the cement slurry.The study reveals that during the circulation flushing stage,the maximum temperature point in the wellbore is located at a distance of about 366 m above the bottom of the well.In the wellbore preparation stage,due to static heat exchange,the maximum temperature point gradually shifts to the bottom of the well.The BHCT of cement slurry changes continuously under cementing processes with multi-fluid and multi-step,making it a transient value.The BHCT of the lead slurry and tail slurry are not equal,with the maximum BHCT of the tail slurry being 2.46°C higher than that of the lead slurry.If circulation flushing and wellbore preparation are not considered,the calculated BHCT of the cement slurry will have errors of+6.8%and-1.9%.The study highlighted that considering thermal effects of all cementing stages,such as circulation flushing and wellbore preparation,in BHCT calculations can help improve prediction accuracy.
基金Hebei Provincial Health Commission Project,No.20210876.
文摘BACKGROUND Circulating tumor cells(CTCs)are crucial for improving our knowledge regarding tumor progress,prognosis,and recurrence possibility.AIM To evaluate the role of CTCs in the early diagnosis and treatment of gastric cancer.METHODS From June 2020 to December 2021,a randomized study was conducted in our institution involving 80 patients scheduled for surgery for gastric cancer.The patients were divided into two groups:A control group that was tested for traditional serum markers and a study group that was assessed for serum CTCs.RESULTS In the study cohort,CTC levels did not correlate significantly with patient age,gender,or degree of tumor differentiation(P>0.05).However,there was a significant correlation with the tumor-node-metastasis stage of the tumor(P<0.05).In the study group,the CTC diagnostic positivity rate was 62.50%(25 out of 40 patients),while the positivity rate for conventional serum markers in the control group was 47.50%(19 out of 40 patients).The positive detection rate in the study group was significantly higher than that of the control group(P<0.05).CONCLUSION CTCs have slight invasion and high sensitivity and specificity,presenting great value for early clinical diagnosis of recurrence and metastasis.It will improve the deceleration of disease development and increase the survival rate.
基金Supported by China Postdoctoral Science Foundation,No.2024M751334.
文摘BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer(GC)patients.To optimize treatment stratification and management,there is an urgent need for efficient and non-invasive biomarkers.A meta-analysis on the prognostic role of circulating tumor cells(CTCs)in GC revealed a strong association between CTCs and patient prognosis.Among CTC subtypes,Interstitial CTCs(I-CTCs)exhibited the strongest invasiveness.This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC.To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients.To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020.The expression levels of I-CTCs were measured,and patient survival was monitored.The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels.Based on this cut-off value,59 GC patients were grouped into positive and negative groups.The differences in clinicopathological characteristics between the two groups were analyzed.Patient survival was follow-up and recorded until October 2022.Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors.The Kaplan-Meier method and Cox regression model were used,respectively.RESULTS A total of 59 patients were included in this study,and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5,with an area under the curve of 0.8356(95%CI:0.7122-0.9590).The I-CTC count of≥5 defines the positive group,while counts<5 are classified as the negative group.Positive I-CTCs correlated with the degree of tumor differentiation and disease progression(P<0.05).16 of 59 patients received neoadjuvant chemotherapy.There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy.Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group(P<0.05).Multifactorial analysis revealed that I-CTCs positivity(HR=13.323,95%CI:1.675-105.962,P=0.014)was an independent risk factor for survival in patients with advanced GC.CONCLUSION In patients with advanced GC,an I-CTC count of≥5 is associated with both poor prognosis and reduced chemotherapy efficacy.I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
基金Supported by Natural Science Foundation of Hubei Province(No.2023AFC019,No.2020CFB240)Hubei Key Laboratories Opening Project(No.2023KFH019,No.2021KFY055)Fundamental Research Funds for Central Universities(No.2042020kf0065).
文摘AIM:To explore the causal links among circulating inflammatory proteins(CIPs)and the varying severities of diabetic retinopathy(DR).METHODS:This research utilized a two sample Mendelian randomization(MR)approach to explore the causal relationships between 91 CIPs and various severities of DR:background DR(BDR)or non-proliferative DR(NPDR),and proliferative DR(PDR).Single-nucleotide polymorphisms(SNPs)related to the 91 CIPs as exposure factors were identified.These SNPs were selected from an extensive genome-wide association study(GWAS)analyzing large genomic datasets.Genetic variation data of various DR phenotypes provided by the FinnGen collaboration were utilized as outcomes.Inverse-variance weighting(IVW)was used as the main MR analysis.Robustness of study results was evaluated through a series of sensitivity analyses,employing the MR-pleiotropy-test and mendelian randomization pleiotropy residual sum and outlier(MR-PRESSO)to confirm the absence of pleiotropy.RESULTS:In a bidirectional MR analysis,we uncovered a complex relationship between CIPs and DR.Elevated levels of tumor necrosis factor ligand superfamily member 14(TNFSF14),latency associated peptide transforming growth factors beta-1(LAP-TGF-beta1),interleukin-10(IL-10),and vascular endothelial growth factor A(VEGF-A)were associated with a reduced risk of NPDR.Conversely,elevated levels of fibroblast growth factor 23(FGF-23)were associated with an increased risk of NPDR.Concentrations of adenosine deaminase(ADA),matrix metalloproteinase-10(MMP-10),eotaxin,and IL-10 showed elevated levels and were linked to a reduced risk of NPDR.On the other hand,the levels of oncostatin-M,beta-nerve growth factor(β-NGF),and interleukin-7(IL-7)were elevated and associated with an increased risk of SNPDR.Elevated levels of ADA,MMP-10,and macrophage colony-stimulating factor 1(CSF1)were linked to a lower likelihood of PDR.Conversely,elevated levels of Caspase 8 and glial cell line-derived neurotrophic factor(GDNF)were associated with an increased risk of PDR.In reverse MR analysis,DR affected the expression of these factors.CONCLUSION:Our research demonstrates evidence supporting a potential causal link between key inflammatory factors and the risk and prognosis of various DR phenotypes.These findings emphasize the regulation of inflammatory factors responses as a strategic approach for preventing and managing DR.Altogether,our results validate the pathogenic role of inflammatory factors dysregulation in DR and support the rationale for exploring immunotherapeutic targets further.
基金supported by the National Natural Science Foundation of China(Grant No.51977046)Wuxi University Research Start-up Fund for Introduced Talent(2022r021).
文摘The development of renewable energy power generation for carbon neutrality and energy transition has been increasing worldwide,leading to an increasing demand for high-power conversion.Compared with traditional interleaved paralleling,the integrated paralleling of three-level inverters can further reduce the output harmonics.Moreover,a well-designed switching sequence ensures that the average circulating current is zero,which provides a superior and feasible solution to satisfy the demands of high-power operations.However,a large instantaneous loop current exists between shunt converters,which leads to disadvantages such as higher switching device stress and loss.In this study,by utilizing the state-distribution redundancy provided by the integrated modulation process,a new design for switch-ing sequences is suggested for the integrated modulation of shunt three-level converters.This design aims to reduce the circulating current while better preserving the same output current harmonics than traditional parallel methods.The proposal includes an in-depth analysis and explanation of the implementation process.Finally,the proposed method is validated through simulations and prototype experi-ments.The results indicate that compared with traditional methods,the adoption of the improved switching sequence presented in this study leads to an average reduction of 3.2%in the total harmonic distortion of the inverter’s output and an average decrease of 32%in the amplitude of the circulating current.Both the output harmonics and circulating currents are significantly suppressed across various modulation indices.
基金Supported by the Council for Science,Technology,and Innovation(CSTI)Cross-Ministerial Strategic Innovation Promotion Program(SIP)“Innovative AI Hospital System”(National Institute of Biomedical Innovation,Health and Nutrition),No.SIPAIH18C03the Japan Society for the Promotion of Science(JSPS)KAKENHI,No.JP19K09179 and No.JP23K08158.
文摘BACKGROUND Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma(PDAC)may have distant metastases,undetected on preoperative imaging or early recurrence,within 6 months after surgery.Occult metastases(OMs)must be accurately predicted to optimize multidisciplinary treatment.AIM To investigate the efficacy of circulating tumor DNA(ctDNA)in predicting OM.METHODS Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.RESULTS Among 135 PDAC patients,38 had OM and 35 were positive for ctDNA.The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM.ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients.Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.CONCLUSION Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.
