It is well established that in the pathology of the cardio-vascular system (CVS) only a portion of the blood volume (BV) can be in active circulation. This portion of BV is named the actively circulating volume (ACV) ...It is well established that in the pathology of the cardio-vascular system (CVS) only a portion of the blood volume (BV) can be in active circulation. This portion of BV is named the actively circulating volume (ACV) and is evaluated from a monotone decrease of dilution curve produced by an intravascular tracer. In given paper is presented Markov chain as a math model of the flow of a tracer throughout CVS. The consideration of CVS as a set of segments with respect to an anatomical structure and assuming the existence for CVS steady-state condition;leads to the Markov chain of the finite order with constant coefficients. The conclusions of the article are 1) there are open and closed microvessels, such that the switching from open to closed and back is a stochastic process, 2) if the switching is slow then the ACV, as the volume of heart chambers and only open for circulation vessels, can be detected.展开更多
Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed...Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm~3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm~3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm~3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm~3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.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
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
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
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
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
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
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
Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,pr...Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,progression,therapeutic resistance,and metastasis.BCSCs self-renew and drive intertumoral heterogeneity,while CTCs disseminate from primary tumors into the bloodstream,seeding distant sites.These populations share molecular features,including stemness and epithelial-mesenchymal transition markers,supporting the concept that a subset of CTCs acquires stem-like traits,enhancing metastatic potential and resistance to standard therapies.This review synthesizes current knowledge on BCSC molecular programs,key signaling pathways(e.g.,Wnt,Notch,Hedgehog,Janus kinase/signal transducer and activator of transcription),and microenvironmental interactions that sustain stemness.It also examines mechanisms of CTC intravasation,state-dependent detection strategies,and their diagnostic and prognostic utility.We further highlight the adaptive plasticity of cancer stem celllike CTCs,their contributions to drug resistance,and opportunities to target these phenotypes for personalized treatment.Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination.As multimodal detection improves and functional profiling matures,integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.展开更多
BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac m...BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.展开更多
Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.Hi...Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.展开更多
BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitiv...BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.展开更多
The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive bi...The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive biosensor was specifically designed for the identification of targeted ctDNA.For the first time,a three-dimensional polyvinylidene fluoride-graphene oxide-chitosan(PVDF/CS/GO)nanofiber mesh was fabricated on a polydimethylsiloxane(PDMS)micropillar substrate using electrospinning technology,and the nanofibers were functionalized with peptide nucleic acids probe-gold nanoparticle(PNA-AuNP)complexes,which served as affinity molecules for detecting the methylation of the E542K variant of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)gene in the peripheral blood of cancer patients.Additionally,an anti-5-Methylcytosine monoclonal antibody-multi-walled carbon nanotubes-COOH complex(Anti-5-mC-MWCNTs-COOH)complex was incubated to result in significantly amplified electrochemical signals for the accurate quantification of the E542K variant of the PIK3CA gene.Detectable signal responses were observed only when both molecules were simultaneously present,greatly enhancing the accuracy of the analysis.The biosensor exhibits high capture sensitivity for the methylation level of the E542K variant of the PIK3CA gene across a concentration range of 50 to 10000 fmol/L,with the lowest detection limit of 10 fmol/L.The ctDNA nanobiosensor has been shown to be both feasible and valuable for quantifying ctDNA concentrations in clinical blood samples.Consequently,this 3D nanofiber biosensor shows significant potential for clinical applications in cancer diagnosis and personalized medical treatments.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
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
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
文摘It is well established that in the pathology of the cardio-vascular system (CVS) only a portion of the blood volume (BV) can be in active circulation. This portion of BV is named the actively circulating volume (ACV) and is evaluated from a monotone decrease of dilution curve produced by an intravascular tracer. In given paper is presented Markov chain as a math model of the flow of a tracer throughout CVS. The consideration of CVS as a set of segments with respect to an anatomical structure and assuming the existence for CVS steady-state condition;leads to the Markov chain of the finite order with constant coefficients. The conclusions of the article are 1) there are open and closed microvessels, such that the switching from open to closed and back is a stochastic process, 2) if the switching is slow then the ACV, as the volume of heart chambers and only open for circulation vessels, can be detected.
基金supported by a grant from the National Health and Family Planning Commission of China(No.201402011)
文摘Objective: We investigated the correlation between the number of circulating tumor cells(CTCs) and wholebody metabolic tumor volume(WBMTV) measured by 18 F-fluorodeoxyglucose(FDG) positron emission tomography/computed tomography(PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage III small-cell lung cancer(SCLC).Methods: One hundred and twenty-nine patients were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy(as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH? system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival(OS) and progression-free survival(PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results: The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy(P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis(Group A: CTC count >19.5 and a WBMTV >266.5cm~3;Group B: CTC count >19.5 and a WBMTV ≤266.5cm~3; Group C: CTC count ≤19.5 and a WBMTV >266.5cm~3;Group D: CTC count ≤19.5 and a WBMTV ≤266.5cm~3) showed that the differences were statistically significant in the median PFS(Group A vs.D,P<0.001; Group B vs.D,P=0.018; Group C vs.D,P=0.029) and in the median OS(Group A vs.D,P<0.001; Group B vs.D,P=0.012).Conclusions: CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.
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.
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 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.
文摘Breast cancer remains a leading cause of cancer-related death in women worldwide.Emerging evidence highlights the central roles of breast cancer stem cells(BCSCs)and circulating tumor cells(CTCs)in tumor initiation,progression,therapeutic resistance,and metastasis.BCSCs self-renew and drive intertumoral heterogeneity,while CTCs disseminate from primary tumors into the bloodstream,seeding distant sites.These populations share molecular features,including stemness and epithelial-mesenchymal transition markers,supporting the concept that a subset of CTCs acquires stem-like traits,enhancing metastatic potential and resistance to standard therapies.This review synthesizes current knowledge on BCSC molecular programs,key signaling pathways(e.g.,Wnt,Notch,Hedgehog,Janus kinase/signal transducer and activator of transcription),and microenvironmental interactions that sustain stemness.It also examines mechanisms of CTC intravasation,state-dependent detection strategies,and their diagnostic and prognostic utility.We further highlight the adaptive plasticity of cancer stem celllike CTCs,their contributions to drug resistance,and opportunities to target these phenotypes for personalized treatment.Clarifying the biological links between BCSCs and CTCs could enable earlier detection of hidden metastasis and inform combination therapies aimed at both stemness and dissemination.As multimodal detection improves and functional profiling matures,integrating BCSC/CTC analyses into routine care may refine risk stratification and guide individualized management.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.
基金supported by the funding from National Natural Science Foundation of China(Nos.32025021,12374390,31971292,82072032,82202274)Ningbo 3315 Innovative Teams Program(No.2019A-14-C)+6 种基金The member of Youth Innovation Promotion Association Foundation of CAS(No.2023310)Key Scientific and Technological Special Project of Ningbo City(Nos.2023Z209,2020Z189)National Key R&D Program of China(No.2019YFA0405603)Provincial Natural Science Foundation of Zhejiang(Nos.LQ23H180007,LQ23H180003)Zhejiang Province Science and Technology Plan of Traditional Chinese Medicine(No.2021KY085)Zhejiang Provincial Traditional Chinese Medicine Foundation(No.2021ZB04)the Major Medical and Health Science and Technology Project of Zhejiang Province(No.WKJ-ZJ-2002)。
文摘Early diagnosis and accurate boundary delineation are the key steps of tumor precision medicine.Circulating tumor cells(CTCs)detection of liquid biopsy can provide abundant information for early diagnosis of cancer.High detection specificity and good enrichment features are two key factors for CTCs accurate identification in peripheral blood sample.For this purpose,iron oxide(IO)-based surface-enhanced Raman scattering(SERS)bioprobes with good biocompatibility,high detection sensitivity,remarkable detection specificity,and good enrichment efficiency,were developed for detecting different types of CTCs.Magnetic SERS bioprobes combined with programmed death ligand-1(PD-L1)antibody are regarded as an effective way to boost the targeting ability and detection specificity,benefiting for accurately capturing and identifying rare CTCs.Four types of CTCs with different PD-L1 expression were accurately distinguished among white blood cells via high-resolution SERS mapping images and stable Raman signals.Subsequently,CTCs blood samples obtained from the triple negative breast cancer patients were also successfully recognized compared to that of health people,indicating IO@AR@PDA-a PD-L1 SERS bioprobe possessed great potential for CTCs detection in liquid biopsy.Additionally,IO-based bioprobe exhibited excellent dual-modal imaging abilities of high-resolution SERS imaging mode and microimaging magnetic resonance imaging mode.These two highly complementary imaging modes endowed IO-based bioprobes unrivalled capacity in tumor boundary differentiation,supporting tumor accurate resection and precise surgery.To our best knowledge,this is the first time that biocompatible IO-based SERS bioprobes without noble metal element were reported not only for CTCs accurate detection,but also for precise tumor boundary delineation,showing great advantages in tumor diagnosis and treatment.
基金Supported by Beijing Bethune Charitable Foundation and Provincial Natural Science Foundation of Liaoning,No.2022-MS-190.
文摘BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.
基金Funded by the National Natural Science Foundation of China(No.11804121)Special Funds for Central Guiding Local Scientific and Technological Development Project(No.2016ZYYD049)。
文摘The detection of circulating tumor DNA(ctDNA)with high sensitivity and specificity is crucial for the early diagnosis and monitoring of tumors,as well as for drug therapy.In this study,a simple and highly sensitive biosensor was specifically designed for the identification of targeted ctDNA.For the first time,a three-dimensional polyvinylidene fluoride-graphene oxide-chitosan(PVDF/CS/GO)nanofiber mesh was fabricated on a polydimethylsiloxane(PDMS)micropillar substrate using electrospinning technology,and the nanofibers were functionalized with peptide nucleic acids probe-gold nanoparticle(PNA-AuNP)complexes,which served as affinity molecules for detecting the methylation of the E542K variant of the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)gene in the peripheral blood of cancer patients.Additionally,an anti-5-Methylcytosine monoclonal antibody-multi-walled carbon nanotubes-COOH complex(Anti-5-mC-MWCNTs-COOH)complex was incubated to result in significantly amplified electrochemical signals for the accurate quantification of the E542K variant of the PIK3CA gene.Detectable signal responses were observed only when both molecules were simultaneously present,greatly enhancing the accuracy of the analysis.The biosensor exhibits high capture sensitivity for the methylation level of the E542K variant of the PIK3CA gene across a concentration range of 50 to 10000 fmol/L,with the lowest detection limit of 10 fmol/L.The ctDNA nanobiosensor has been shown to be both feasible and valuable for quantifying ctDNA concentrations in clinical blood samples.Consequently,this 3D nanofiber biosensor shows significant potential for clinical applications in cancer diagnosis and personalized medical treatments.
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 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.
