Dear Editor,The ongoing emergence of circulating recombinant forms(CRFs)of HIV-1 was recently reported among men who have sex with men(MSM)in China(Xiao et al.,2025;Xing et al.,2024).HIV-1’s global diversity is class...Dear Editor,The ongoing emergence of circulating recombinant forms(CRFs)of HIV-1 was recently reported among men who have sex with men(MSM)in China(Xiao et al.,2025;Xing et al.,2024).HIV-1’s global diversity is classified into four groups:M(Major,causing the pandemic),O(Outlier),N,and P.Group M,the most prevalent,is subdivided into subtypes(A-D,F-H and J-L).Recombinant viruses formed between subtypes are classified as either stable CRFs spreading in populations or unique recombinant forms(URFs).HIV-1 recombination significantly complicates HIV genetics and has the capacity to directly alter key viral properties.展开更多
Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian can...Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian cancer(OC).This study evaluated the diagnostic and prognostic significance of chromosome 8aneuploidy in CTCs and circulating tumor endothelial cells(CTECs)for preoperative diagnosis,treatment efficacy assessment,and recurrence monitoring.Methods:A total of 331 patients were enrolled,including 56 with newly diagnosed primary OC,265 with benign ovarian tumors,and 10 with borderline tumors.Peripheral blood CTCs and CTECs were detected using SEi FISH;their quantity and ploidy characteristics were analyzed in relation to clinical indicators.To assess dynamic CTC changes during disease progression and treatment response,72 patients were followed longitudinally,of whom 19 experienced recurrence.Results:The CTC detection rate in OC patients was 92.9%,with significantly higher counts than that in the benign tumor group(median 5 vs.2).Receiver operating characteristic analysis demonstrated good diagnostic performance for total CTCs[area under the curve(AUC)=0.699],with triploid CTCs achieving the highest efficacy(AUC=0.792),surpassing carbohydrate antigen 125(CA125)(AUC=0.702).Postoperative follow-up showed that70%of patients exhibited concurrent decreases in CTCs and CA125 levels,indicating disease improvement.In30%of patients,CTC levels did not correlate with changes in CA125 levels.Individual case evidence suggests that CTC alterations may serve as an early indicator of recurrence or metastasis.Among the 19 recurrent cases,73.7%showed elevated CTCs at recurrence that decreased following treatment.In four patients,CTCs reflected disease progression earlier than CA125,indicating higher sensitivity for recurrence monitoring.Conclusions:CTCs with chromosome 8 aneuploidy demonstrate significant clinical value in the preoperative diagnosis,treatment efficacy evaluation,and recurrence monitoring of OC.Dynamic CTC changes may serve as a more sensitive indicator than CA125 for disease surveillance,supporting the translational potential of CTC-based biomarkers in OC.展开更多
Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be d...Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.展开更多
Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and res...Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch■system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.展开更多
Objectives:Circulating tumor cells(CTCs)drive metastasis and exhibit resistance to conventional therapies,making them crucial therapeutic targets.Artesunate(AS),a derivative of artemisinin,displays anticancer activity...Objectives:Circulating tumor cells(CTCs)drive metastasis and exhibit resistance to conventional therapies,making them crucial therapeutic targets.Artesunate(AS),a derivative of artemisinin,displays anticancer activity,including inhibition of JunB proto-oncogene(JUNB)and programmed death ligand-1(PD-L1)and upregulation of Vimentin(VIM),markers related to poor prognosis in CTCs.This study aimed to evaluate the effects of AS on adherent and non-adherent cancer cell lines(breast,lung,colon),the patient-derived colon cancer CTC-MCC-41 line,and CTCs from small-cell lung cancer(SCLC)patients.Methods:AS’s effect was evaluated using TetherChip technology.Cell viability was measured using MTT assay,while immunofluorescence staining and the VyCAP platform were applied to characterize and quantify CTCs.Results:AS significantly reduces viability in all tested cell lines in a time-and concentration-dependent manner,with non-adherent cells showing higher resistance.Notably,CTC-MCC-41 cells are the most sensitive to AS treatment.AS demonstrates stronger cytotoxicity than 5-fluorouracil(5-FU)in most cancer models.In SCLC patient samples,AS reduces total CTC counts(p<0.001),eliminates aggressive phenotypes such as(CK+/CXCR4+/JUNB–)and(CK+/VIM+/GLU+),and increases apoptotic(M30+)CTCs(p=0.021).AS additionally impairs structural features like microtentacles,which facilitate CTC reattachment.Conclusions:These findings underscore AS’s ability to target metastasis-competent and anoikis-resistant tumor cells,reducing their viability,invasiveness,and survival mechanisms.AS emerges as a promising candidate for anti-metastatic therapy and warrants further investigation in precision oncology.展开更多
BACKGROUND Despite emerging evidence supporting circulating tumor DNA(ctDNA)as a potential biomarker for pancreatic ductal adenocarcinoma(PDAC),its clinical efficacy for serial monitoring has not been thoroughly explo...BACKGROUND Despite emerging evidence supporting circulating tumor DNA(ctDNA)as a potential biomarker for pancreatic ductal adenocarcinoma(PDAC),its clinical efficacy for serial monitoring has not been thoroughly explored.We hypothesized that serial monitoring of ctDNA provides clinically relevant information on treatment response and prognosis in patients with PDAC.AIM To investigate the feasibility of using longitudinal ctDNA monitoring to predict treatment response and prognostic outcomes in patients with PDAC.METHODS This prospective observational study enrolled patients with PDAC confirmed histologically by biopsy.Blood samples were collected at baseline and during follow-up for ctDNA analysis using droplet digital polymerase chain reaction targeting KRAS G12/G13 mutations.Patients with PDAC were divided into resection and chemotherapy groups for further analysis.Radiologic responses were compared with changes in ctDNA(ΔctDNA)and carbohydrate antigen 19-9.Survival outcomes were analyzed based on the baseline ctDNA levels and clearance status.RESULTS Of the 200 enrolled patients,168 were eligible for ctDNA detection rate analysis using the droplet digital polymerase chain reaction and 139 underwent serial ctDNA monitoring(34 resection group,105 chemotherapy group).The overall ctDNA detection rate was 80.4%.Higher rates were observed in advanced disease stages(P=0.004)and liver metastasis(P=0.031).In the resection group,ΔctDNA did not differ significantly between the recurrence and non-recurrence groups.However,in the chemotherapy group,ΔctDNA showed significant differences among response groups(P0.418)were associated with shorter progressionfree survival(4.7 months vs 7.5 months,P=0.024)and OS(9.7 months vs 15.9 months,P=0.039).In addition,ctDNA clearance at 8 weeks after chemotherapy was associated with improved OS(18.8 months vs 11.4 months,P=0.031).CONCLUSION Serial ctDNA monitoring is a promising biomarker for treatment response and prognosis of PDAC,particularly in advanced disease.展开更多
Background:Pediatric sarcomas are aggressive malignancies characterized by marked biological heterogeneity and a high risk of relapse.Standard surveillance relies on imaging and invasive biopsies,which may fail to det...Background:Pediatric sarcomas are aggressive malignancies characterized by marked biological heterogeneity and a high risk of relapse.Standard surveillance relies on imaging and invasive biopsies,which may fail to detect early molecular disease.Liquid biopsy using circulating tumor DNA(ctDNA)and microRNAs offers a minimally invasive strategy for longitudinal monitoring.This study aimed to evaluate dynamic changes in ctDNA and circulating microRNAs during treatment and examined their associations with treatment response,disease recurrence,and survival outcomes.Methods:This prospective cohort study included 100 pediatric patients with histologically confirmed sarcomas.Serial peripheral blood samples were collected at diagnosis,during treatment,at treatment completion,and during follow-up.Plasma-derived ctDNA and miRNAs were quantified using droplet digital Polymerase Chain Reaction(PCR)and quantitative Reverse Transcriptase-PCR(qRT-PCR).Associations between biomarker levels,clinical and radiologic response,recurrence,and survival outcomes were analysed using correlation analyses.Results:The mean age at diagnosis was 10.5±4.9 years,with a male predominance(59.0%).The most common tumor subtype was Ewing sarcoma(49.0%),followed by rhabdomyosarcoma(27.0%)and osteosarcoma(24.0%).Both ctDNA and circulating miRNA concentration declined significantly from baseline to the end of treatment(p0.05).In multivariable analysis,disease recurrence status was strongly associated with survival,as expected;however,circulating biomarker levels did not independently predict outcome(Odds ratio(OR)=0.04,95%Confidence Interval(CI):0.01–0.15;p<0.001).Conclusions:ctDNA and microRNA levels showed dynamic,treatment-related changes in pediatric sarcomas,reflecting therapeutic response at the population level.However,single end-of-treatment measurements were not predictive of outcomes.These findings support liquid biopsy for longitudinal monitoring rather than static prognostication and emphasize the need for prospective validation of serial biomarker approaches.展开更多
Circulating tumor cells(CTCs)are cells that become detached from a primary tumor and enter the vascular or lymphatic system.These cells contain nearly the entire genetic information of the primary tumor.Enrichment and...Circulating tumor cells(CTCs)are cells that become detached from a primary tumor and enter the vascular or lymphatic system.These cells contain nearly the entire genetic information of the primary tumor.Enrichment and detection of CTCs play a crucial role in prognostications and risk assessments of tumor metastasis and recurrence,evaluation of efficacy and potential medications for precision tumor therapy,and detection of dynamic biomarkers during tumor treatment.Current methods of CTC capture often face the challenge of balancing capture rate and purity.To address these issues,we propose a microfluidic biochip based on the principle of immunoaffinity,which incorporates a herringbone microchannel and deterministic lateral displacement(DLD)technology for the capture of CTCs.By manipulating the internal structural design of the microfluidic chip,we optimized the flow field within the chip,thereby enhancing the contact frequency between cells and aptamers and ultimately improving the capture rate.The proposed chip demonstrated a capture efficiency of approximately 91.87%for human breast cancer cells(MCF7),with a release rate of 77.5%.The relative activity of the released cells was approximately 94.08%.Notably,the specificity of the aptamers toward tumor cell surface antigens enables high-purity capture.Additionally,the use of DNA enzymes to digest aptamers facilitates the release of high-activity CTCs,offering a method to simultaneously achieve a high capture rate,purity,and activity enrichment.展开更多
BACKGROUND Circulating tumor cells(CTCs)are promising minimally invasive biomarkers for tumor biology and metastasis.Although their clinical value has been established in several cancers,the evidence supporting their ...BACKGROUND Circulating tumor cells(CTCs)are promising minimally invasive biomarkers for tumor biology and metastasis.Although their clinical value has been established in several cancers,the evidence supporting their role in gastric cancer remains inconsistent and warrants further validation.AIM To investigate the prognostic value of preoperative CTCs detection in patients with gastric cancer.METHODS A retrospective analysis of patients with pathologically confirmed gastric adenocarcinoma who underwent preoperative testing of peripheral blood CTCs at the Department of Gastric and Small Intestinal Surgery,Zhangzhou Hospital,Fujian Province between June 2020 and March 2021 was performed.Correlations between preoperative CTCs status and clinicopathological characteristics as well as prognosis were evaluated.RESULTS Among the 115 patients newly diagnosed with gastric cancer,61(53.04%)were CTCs-positive and 54(46.96%)were CTCs-negative.Significant differences were observed between the CTCs-positive and CTCs-negative groups in terms of tumor differentiation,lymph node metastasis,distant metastasis,pathologic tumour,node,and metastasis stage,and coagulation parameters(activated partial thromboplastin time,thrombin time,D-dimer level,and platelet count)(all P0.05).Univariate Cox regression analysis identified tumor size,depth of invasion,lymph node and distant metastases,tumor stage,neural invasion,vascular invasion,and CTCs positivity as risk factors for poor prognosis in patients with gastric cancer.At the follow-up cutoff date,recurrence or metastasis had occurred in 28 CTCs-positive patients(45.90%)and 15 CTCs-negative patients(27.78%).The CTCs-positive group exhibited higher rates of distant metastasis(78.57%vs 66.67%,P=0.394)and peritoneal metastasis(64.29%vs 46.67%,P=0.264)than the CTCs-negative group.Additionally,the CTCs-positive group had significantly shorter progression-free survival(PFS)(32.72 months vs 39.96 months,P=0.036)and a trend toward reduced overall survival(38.62 months vs 41.11 months,P=0.411).CONCLUSION Preoperative CTCs detection is associated with aggressive biological behavior in gastric cancer and has predictive value for PFS.Based on these findings,we recommend integrating preoperative CTCs testing into the clinical management of patients to improve risk stratification and guide personalized treatment strategies.Further prospective studies are warranted to validate the utility of optimizing surveillance protocols and therapeutic decisions.展开更多
BACKGROUND Accurate assessment of lymph node metastasis(LNM)is important in patients with esophageal cancer(EC).AIM To construct machine learning(ML)models using routine clinical data to predict LNM in patients with E...BACKGROUND Accurate assessment of lymph node metastasis(LNM)is important in patients with esophageal cancer(EC).AIM To construct machine learning(ML)models using routine clinical data to predict LNM in patients with EC,exploring predictive capacity after integrating circulating tumor DNA(ctDNA)features.METHODS In this retrospective study,we collected demographic information,risk factors,protein biomarkers,computed tomography(CT),endoscopic,and pathological data of 206 patients with EC.The ctDNA data were available for 57 patients.A total of 81 models were developed using different feature-selection techniques and ML algorithms.A total of 79(38.3%)patients had pathologically confirmed LNM.RESULTS The different ML models demonstrated good predictive performance,with a median area under the curve(AUC)of 0.767(interquartile range:0.679,0.828)and median F1 score of 0.715(interquartile range:0.672,0.772).The variables were selected through univariate and multivariate logistic analyses and the best model was constructed using the random forest algorithm.It incorporated tumor length,location,CT results,depth of tumor invasion,and number of aberrant protein biomarkers.It demonstrated an AUC of 0.79(95%CI:0.65-0.93)and accuracy of 82.26%(95%CI:70.47%-90.80%),which were superior to the CT results.Incorporating ctDNA features yielded modest improvements in AUC(9.0%)and F1 score(14.3%);however,these gains were not statistically significant.CONCLUSION Combining ctDNA features with preoperative clinical factors and CT results can enhance the predictive ability of LNM models in patients with EC.展开更多
The circulating microbiome,comprised of microbial DNA,metabolites,and cellderived fragments,has emerged as a potential contributor to the pathophysiology of diabetes mellitus.This review summarizes current evidence on...The circulating microbiome,comprised of microbial DNA,metabolites,and cellderived fragments,has emerged as a potential contributor to the pathophysiology of diabetes mellitus.This review summarizes current evidence on how microbial translocation and blood-borne microbial components influence metabolic and immune dysfunction in type 1 and type 2 diabetes.Quantitative studies report elevated circulating lipopolysaccharide levels(often>2-fold higher in diabetic cohorts),increased trimethylamine-N-oxide,and reduced short-chain fatty acids,all of which correlate with systemic inflammation,insulin resistance,and glycemic variability.Mechanistic data indicate that microbial products activate Tolllike receptors(TLRs),particularly TLR4 and TLR2,amplifying cytokine release and impairingβ-cell function.Distinct microbial DNA signatures identified through metagenomics further link the circulating microbiome to complications,such as nephropathy,cardiovascular dysfunction,and impaired wound healing.Emerging therapeutic approaches,including microbiome-directed diets,prebiotics,probiotics,and strategies that reduce microbial translocation,show promise in modulating these systemic effects.Despite rapid advances,major gaps remain in establishing causality,standardizing detection methods,and defining clinically actionable microbial biomarkers.Addressing these challenges will be essential for translating circulating microbiome research into diagnostic tools and personalized interventions for diabetes management.展开更多
BACKGROUND Gastrointestinal bleeding(GIB)is a common critical illness,especially in patients in the intensive care unit(ICU),and is often complicated by shock,multiple organ dysfunction,and serious infections,resultin...BACKGROUND Gastrointestinal bleeding(GIB)is a common critical illness,especially in patients in the intensive care unit(ICU),and is often complicated by shock,multiple organ dysfunction,and serious infections,resulting in high mortality.At present,clinical practice mainly relies on the Glasgow-Blatchford,albumin,international normalized ratio,mental status,systolic blood pressure,age≥65 years(AIMS65),and Rockall scoring systems,combined with lactic acid and organ function indicators,to evaluate the condition and prognosis.However,the predictive value of these traditional indicators for short-term mortality in critically ill patients with GIB remains limited,and additional biomarkers are needed to complement,rather than replace,established clinical assessments.AIM To explore associations between circulating stem/progenitor cell biomarkers and prognosis in critically ill GIB patients and develop a prognostic model.METHODS Overall,140 GIB patients admitted to the ICU of Jiashan First People’s Hospital(January 2020 and December 2025)were retrospectively included.Flow cytometry analyzed peripheral blood samples within 6 hours of ICU admission,including CD34+cells,endothelial progenitor cell(EPC)(CD34+KDR+),and EPC(CD34+CD133+KDR+)subsets.The primary outcome was 28-day all-cause death,and secondary outcomes included 7 days rebleeding,90-day death and ICU stay.Multivariate logistic regression analyzed factors associated with 28-day all-cause death,and receiver operating characteristic curve analysis evaluated model discrimination.RESULTS Twenty-nine(20.71%)patients died within 28 days and 29(20.71%)experienced rebleeding within 7 days.Patients in the death group were more critically ill,manifested as higher Sequential Organ Failure Assessment score(10.21±2.15 vs 7.96±3.00,P=0.001),AIMS65 score[4.00(3.00,4.00)vs 3.00(2.00,3.00),P=0.008],proportion of cirrhosis[18(62.07%)vs 27(24.32%),P<0.001],and lactic acid levels[4.20(3.05,5.35)mmol/L vs 2.95(2.28,3.55)mmol/L,P=0.003].Among the circulating progenitor cells,lnEPC(CD34+KDR+)levels were significantly lower in the death group[0.85(0.65,1.15)vs 1.35(1.08,1.60),P<0.001].After adjusting for Sequential Organ Failure Assessment score,lactic acid level,AIMS65 score,and cirrhosis,lnEPCs(CD34+KDR+)remained associated with 28-day mortality(odds ratio=0.557,95%confidence interval:0.353-0.879,P=0.012).The combined model showed moderate discrimination(area under the curve=0.727);at the optimal predicted-probability cutoff of 0.360,the sensitivity and specificity were 0.483 and 0.937,respectively,with acceptable calibration on the Hosmer-Lemeshow test(P=0.622).CONCLUSION A lower early EPC(CD34+KDR+)level was associated with increased short-term mortality in critically ill patients with GIB.The combined EPC-clinical model may complement organ dysfunction assessment and aid supplementary risk stratification.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
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 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
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
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 neoplasticumor 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
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
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 Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This...BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.展开更多
基金supported by the National Natural Science Foundation of China(82160635)the Yunnan Health Training Project of High-Level Talents(L-2024020)the National Public Health Talent Cultivation Support Program.
摘要Dear Editor,The ongoing emergence of circulating recombinant forms(CRFs)of HIV-1 was recently reported among men who have sex with men(MSM)in China(Xiao et al.,2025;Xing et al.,2024).HIV-1’s global diversity is classified into four groups:M(Major,causing the pandemic),O(Outlier),N,and P.Group M,the most prevalent,is subdivided into subtypes(A-D,F-H and J-L).Recombinant viruses formed between subtypes are classified as either stable CRFs spreading in populations or unique recombinant forms(URFs).HIV-1 recombination significantly complicates HIV genetics and has the capacity to directly alter key viral properties.
基金sponsored by the Peking University People’s Hospital Research and Development Fund(No.RDZH2024-06)the National Key Research and Development Program of China(No.2022YFC2704204)。
摘要Objective:We investigated the clinical value of a novel circulating tumor cell(CTC)detection method—subtraction enrichment combined with immunostaining and fluorescence in situ hybridization(SEi FISH)—in ovarian cancer(OC).This study evaluated the diagnostic and prognostic significance of chromosome 8aneuploidy in CTCs and circulating tumor endothelial cells(CTECs)for preoperative diagnosis,treatment efficacy assessment,and recurrence monitoring.Methods:A total of 331 patients were enrolled,including 56 with newly diagnosed primary OC,265 with benign ovarian tumors,and 10 with borderline tumors.Peripheral blood CTCs and CTECs were detected using SEi FISH;their quantity and ploidy characteristics were analyzed in relation to clinical indicators.To assess dynamic CTC changes during disease progression and treatment response,72 patients were followed longitudinally,of whom 19 experienced recurrence.Results:The CTC detection rate in OC patients was 92.9%,with significantly higher counts than that in the benign tumor group(median 5 vs.2).Receiver operating characteristic analysis demonstrated good diagnostic performance for total CTCs[area under the curve(AUC)=0.699],with triploid CTCs achieving the highest efficacy(AUC=0.792),surpassing carbohydrate antigen 125(CA125)(AUC=0.702).Postoperative follow-up showed that70%of patients exhibited concurrent decreases in CTCs and CA125 levels,indicating disease improvement.In30%of patients,CTC levels did not correlate with changes in CA125 levels.Individual case evidence suggests that CTC alterations may serve as an early indicator of recurrence or metastasis.Among the 19 recurrent cases,73.7%showed elevated CTCs at recurrence that decreased following treatment.In four patients,CTCs reflected disease progression earlier than CA125,indicating higher sensitivity for recurrence monitoring.Conclusions:CTCs with chromosome 8 aneuploidy demonstrate significant clinical value in the preoperative diagnosis,treatment efficacy evaluation,and recurrence monitoring of OC.Dynamic CTC changes may serve as a more sensitive indicator than CA125 for disease surveillance,supporting the translational potential of CTC-based biomarkers in OC.
摘要Cervical cancer related to human papillomavirus(HPV)is a leading cause of cancer-related mortality among women worldwide.Cancer cells release fragments of their DNA,known as circulating tumor DNA(ctDNA),which can be detected in bodily fluids.A PubMed search using the terms“ctHPV”or“circulating tumor DNA”and“cervical cancer”,limited to the past ten years,identified 104 articles,complemented by hand-searching for literature addressing medico-legal implications.Studies were evaluated for relevance and methodological quality.Detection and characterization of circulating tumor HPV DNA(ctHPV DNA)have emerged as promising tools for assessing prognosis and disease recurrence in cervical cancer.Detection techniques include polymerase chain reaction(PCR),digital droplet PCR(ddPCR),and next-generation sequencing(NGS).This review summarizes current knowledge on ctHPV DNA in cervical cancer and explores its clinical and medico-legal implications,including management of discordant results,diagnostic errors,liability,and data protection compliance.
基金funded by Sapienza University PNRR-RT_SPOKE_1—ROME TECHNOPOLE—Spoke 1—B83C22002820006—ECS00000024 and FO R.O.onlus.
摘要Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch■system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.
基金financed by the Research Council of the University of Patras.The research project was supported by the project SUB3.Applied Research for Precision Medicine through a Non-Profit Organisation(NPO)under Private Law-”Hellenic Precision Medicine Network“(HPMN),which is co-financed by Recovery and Resilience Fund and the Next Generation EU through the General Secretariat for Research and Innovation of the Hellenic Ministry of Development(MIS 5184864).
摘要Objectives:Circulating tumor cells(CTCs)drive metastasis and exhibit resistance to conventional therapies,making them crucial therapeutic targets.Artesunate(AS),a derivative of artemisinin,displays anticancer activity,including inhibition of JunB proto-oncogene(JUNB)and programmed death ligand-1(PD-L1)and upregulation of Vimentin(VIM),markers related to poor prognosis in CTCs.This study aimed to evaluate the effects of AS on adherent and non-adherent cancer cell lines(breast,lung,colon),the patient-derived colon cancer CTC-MCC-41 line,and CTCs from small-cell lung cancer(SCLC)patients.Methods:AS’s effect was evaluated using TetherChip technology.Cell viability was measured using MTT assay,while immunofluorescence staining and the VyCAP platform were applied to characterize and quantify CTCs.Results:AS significantly reduces viability in all tested cell lines in a time-and concentration-dependent manner,with non-adherent cells showing higher resistance.Notably,CTC-MCC-41 cells are the most sensitive to AS treatment.AS demonstrates stronger cytotoxicity than 5-fluorouracil(5-FU)in most cancer models.In SCLC patient samples,AS reduces total CTC counts(p<0.001),eliminates aggressive phenotypes such as(CK+/CXCR4+/JUNB–)and(CK+/VIM+/GLU+),and increases apoptotic(M30+)CTCs(p=0.021).AS additionally impairs structural features like microtentacles,which facilitate CTC reattachment.Conclusions:These findings underscore AS’s ability to target metastasis-competent and anoikis-resistant tumor cells,reducing their viability,invasiveness,and survival mechanisms.AS emerges as a promising candidate for anti-metastatic therapy and warrants further investigation in precision oncology.
基金Supported by National Research Foundation of Korea,No.RS-2021-NR059201the Seoul National University Bundang Hospital Research Fund,No.06-2019-0069.
摘要BACKGROUND Despite emerging evidence supporting circulating tumor DNA(ctDNA)as a potential biomarker for pancreatic ductal adenocarcinoma(PDAC),its clinical efficacy for serial monitoring has not been thoroughly explored.We hypothesized that serial monitoring of ctDNA provides clinically relevant information on treatment response and prognosis in patients with PDAC.AIM To investigate the feasibility of using longitudinal ctDNA monitoring to predict treatment response and prognostic outcomes in patients with PDAC.METHODS This prospective observational study enrolled patients with PDAC confirmed histologically by biopsy.Blood samples were collected at baseline and during follow-up for ctDNA analysis using droplet digital polymerase chain reaction targeting KRAS G12/G13 mutations.Patients with PDAC were divided into resection and chemotherapy groups for further analysis.Radiologic responses were compared with changes in ctDNA(ΔctDNA)and carbohydrate antigen 19-9.Survival outcomes were analyzed based on the baseline ctDNA levels and clearance status.RESULTS Of the 200 enrolled patients,168 were eligible for ctDNA detection rate analysis using the droplet digital polymerase chain reaction and 139 underwent serial ctDNA monitoring(34 resection group,105 chemotherapy group).The overall ctDNA detection rate was 80.4%.Higher rates were observed in advanced disease stages(P=0.004)and liver metastasis(P=0.031).In the resection group,ΔctDNA did not differ significantly between the recurrence and non-recurrence groups.However,in the chemotherapy group,ΔctDNA showed significant differences among response groups(P0.418)were associated with shorter progressionfree survival(4.7 months vs 7.5 months,P=0.024)and OS(9.7 months vs 15.9 months,P=0.039).In addition,ctDNA clearance at 8 weeks after chemotherapy was associated with improved OS(18.8 months vs 11.4 months,P=0.031).CONCLUSION Serial ctDNA monitoring is a promising biomarker for treatment response and prognosis of PDAC,particularly in advanced disease.
基金funded by the Deanship of Scientific Research(DSR)at King Abdulaziz University,Jeddah,Saudi Arabia,under grant no.(IPP:939-828-2025).
摘要Background:Pediatric sarcomas are aggressive malignancies characterized by marked biological heterogeneity and a high risk of relapse.Standard surveillance relies on imaging and invasive biopsies,which may fail to detect early molecular disease.Liquid biopsy using circulating tumor DNA(ctDNA)and microRNAs offers a minimally invasive strategy for longitudinal monitoring.This study aimed to evaluate dynamic changes in ctDNA and circulating microRNAs during treatment and examined their associations with treatment response,disease recurrence,and survival outcomes.Methods:This prospective cohort study included 100 pediatric patients with histologically confirmed sarcomas.Serial peripheral blood samples were collected at diagnosis,during treatment,at treatment completion,and during follow-up.Plasma-derived ctDNA and miRNAs were quantified using droplet digital Polymerase Chain Reaction(PCR)and quantitative Reverse Transcriptase-PCR(qRT-PCR).Associations between biomarker levels,clinical and radiologic response,recurrence,and survival outcomes were analysed using correlation analyses.Results:The mean age at diagnosis was 10.5±4.9 years,with a male predominance(59.0%).The most common tumor subtype was Ewing sarcoma(49.0%),followed by rhabdomyosarcoma(27.0%)and osteosarcoma(24.0%).Both ctDNA and circulating miRNA concentration declined significantly from baseline to the end of treatment(p0.05).In multivariable analysis,disease recurrence status was strongly associated with survival,as expected;however,circulating biomarker levels did not independently predict outcome(Odds ratio(OR)=0.04,95%Confidence Interval(CI):0.01–0.15;p<0.001).Conclusions:ctDNA and microRNA levels showed dynamic,treatment-related changes in pediatric sarcomas,reflecting therapeutic response at the population level.However,single end-of-treatment measurements were not predictive of outcomes.These findings support liquid biopsy for longitudinal monitoring rather than static prognostication and emphasize the need for prospective validation of serial biomarker approaches.
基金supported by the State Key Laboratory of High performance Precision Manufacturing(No.HPMKF202412)the Zhejiang Provincial Natural Science Foundation of China(No.LZ25E050001)+1 种基金the National Natural Science Foundation of China(No.52275294)the Zhejiang Provincial‘Pioneer Leading Swan+X’Science and Technology Program(No.2025C02122),China.
摘要Circulating tumor cells(CTCs)are cells that become detached from a primary tumor and enter the vascular or lymphatic system.These cells contain nearly the entire genetic information of the primary tumor.Enrichment and detection of CTCs play a crucial role in prognostications and risk assessments of tumor metastasis and recurrence,evaluation of efficacy and potential medications for precision tumor therapy,and detection of dynamic biomarkers during tumor treatment.Current methods of CTC capture often face the challenge of balancing capture rate and purity.To address these issues,we propose a microfluidic biochip based on the principle of immunoaffinity,which incorporates a herringbone microchannel and deterministic lateral displacement(DLD)technology for the capture of CTCs.By manipulating the internal structural design of the microfluidic chip,we optimized the flow field within the chip,thereby enhancing the contact frequency between cells and aptamers and ultimately improving the capture rate.The proposed chip demonstrated a capture efficiency of approximately 91.87%for human breast cancer cells(MCF7),with a release rate of 77.5%.The relative activity of the released cells was approximately 94.08%.Notably,the specificity of the aptamers toward tumor cell surface antigens enables high-purity capture.Additionally,the use of DNA enzymes to digest aptamers facilitates the release of high-activity CTCs,offering a method to simultaneously achieve a high capture rate,purity,and activity enrichment.
基金Supported by Natural Science Foundation of Fujian Province,No.2024J011567.
摘要BACKGROUND Circulating tumor cells(CTCs)are promising minimally invasive biomarkers for tumor biology and metastasis.Although their clinical value has been established in several cancers,the evidence supporting their role in gastric cancer remains inconsistent and warrants further validation.AIM To investigate the prognostic value of preoperative CTCs detection in patients with gastric cancer.METHODS A retrospective analysis of patients with pathologically confirmed gastric adenocarcinoma who underwent preoperative testing of peripheral blood CTCs at the Department of Gastric and Small Intestinal Surgery,Zhangzhou Hospital,Fujian Province between June 2020 and March 2021 was performed.Correlations between preoperative CTCs status and clinicopathological characteristics as well as prognosis were evaluated.RESULTS Among the 115 patients newly diagnosed with gastric cancer,61(53.04%)were CTCs-positive and 54(46.96%)were CTCs-negative.Significant differences were observed between the CTCs-positive and CTCs-negative groups in terms of tumor differentiation,lymph node metastasis,distant metastasis,pathologic tumour,node,and metastasis stage,and coagulation parameters(activated partial thromboplastin time,thrombin time,D-dimer level,and platelet count)(all P0.05).Univariate Cox regression analysis identified tumor size,depth of invasion,lymph node and distant metastases,tumor stage,neural invasion,vascular invasion,and CTCs positivity as risk factors for poor prognosis in patients with gastric cancer.At the follow-up cutoff date,recurrence or metastasis had occurred in 28 CTCs-positive patients(45.90%)and 15 CTCs-negative patients(27.78%).The CTCs-positive group exhibited higher rates of distant metastasis(78.57%vs 66.67%,P=0.394)and peritoneal metastasis(64.29%vs 46.67%,P=0.264)than the CTCs-negative group.Additionally,the CTCs-positive group had significantly shorter progression-free survival(PFS)(32.72 months vs 39.96 months,P=0.036)and a trend toward reduced overall survival(38.62 months vs 41.11 months,P=0.411).CONCLUSION Preoperative CTCs detection is associated with aggressive biological behavior in gastric cancer and has predictive value for PFS.Based on these findings,we recommend integrating preoperative CTCs testing into the clinical management of patients to improve risk stratification and guide personalized treatment strategies.Further prospective studies are warranted to validate the utility of optimizing surveillance protocols and therapeutic decisions.
摘要BACKGROUND Accurate assessment of lymph node metastasis(LNM)is important in patients with esophageal cancer(EC).AIM To construct machine learning(ML)models using routine clinical data to predict LNM in patients with EC,exploring predictive capacity after integrating circulating tumor DNA(ctDNA)features.METHODS In this retrospective study,we collected demographic information,risk factors,protein biomarkers,computed tomography(CT),endoscopic,and pathological data of 206 patients with EC.The ctDNA data were available for 57 patients.A total of 81 models were developed using different feature-selection techniques and ML algorithms.A total of 79(38.3%)patients had pathologically confirmed LNM.RESULTS The different ML models demonstrated good predictive performance,with a median area under the curve(AUC)of 0.767(interquartile range:0.679,0.828)and median F1 score of 0.715(interquartile range:0.672,0.772).The variables were selected through univariate and multivariate logistic analyses and the best model was constructed using the random forest algorithm.It incorporated tumor length,location,CT results,depth of tumor invasion,and number of aberrant protein biomarkers.It demonstrated an AUC of 0.79(95%CI:0.65-0.93)and accuracy of 82.26%(95%CI:70.47%-90.80%),which were superior to the CT results.Incorporating ctDNA features yielded modest improvements in AUC(9.0%)and F1 score(14.3%);however,these gains were not statistically significant.CONCLUSION Combining ctDNA features with preoperative clinical factors and CT results can enhance the predictive ability of LNM models in patients with EC.
摘要The circulating microbiome,comprised of microbial DNA,metabolites,and cellderived fragments,has emerged as a potential contributor to the pathophysiology of diabetes mellitus.This review summarizes current evidence on how microbial translocation and blood-borne microbial components influence metabolic and immune dysfunction in type 1 and type 2 diabetes.Quantitative studies report elevated circulating lipopolysaccharide levels(often>2-fold higher in diabetic cohorts),increased trimethylamine-N-oxide,and reduced short-chain fatty acids,all of which correlate with systemic inflammation,insulin resistance,and glycemic variability.Mechanistic data indicate that microbial products activate Tolllike receptors(TLRs),particularly TLR4 and TLR2,amplifying cytokine release and impairingβ-cell function.Distinct microbial DNA signatures identified through metagenomics further link the circulating microbiome to complications,such as nephropathy,cardiovascular dysfunction,and impaired wound healing.Emerging therapeutic approaches,including microbiome-directed diets,prebiotics,probiotics,and strategies that reduce microbial translocation,show promise in modulating these systemic effects.Despite rapid advances,major gaps remain in establishing causality,standardizing detection methods,and defining clinically actionable microbial biomarkers.Addressing these challenges will be essential for translating circulating microbiome research into diagnostic tools and personalized interventions for diabetes management.
摘要BACKGROUND Gastrointestinal bleeding(GIB)is a common critical illness,especially in patients in the intensive care unit(ICU),and is often complicated by shock,multiple organ dysfunction,and serious infections,resulting in high mortality.At present,clinical practice mainly relies on the Glasgow-Blatchford,albumin,international normalized ratio,mental status,systolic blood pressure,age≥65 years(AIMS65),and Rockall scoring systems,combined with lactic acid and organ function indicators,to evaluate the condition and prognosis.However,the predictive value of these traditional indicators for short-term mortality in critically ill patients with GIB remains limited,and additional biomarkers are needed to complement,rather than replace,established clinical assessments.AIM To explore associations between circulating stem/progenitor cell biomarkers and prognosis in critically ill GIB patients and develop a prognostic model.METHODS Overall,140 GIB patients admitted to the ICU of Jiashan First People’s Hospital(January 2020 and December 2025)were retrospectively included.Flow cytometry analyzed peripheral blood samples within 6 hours of ICU admission,including CD34+cells,endothelial progenitor cell(EPC)(CD34+KDR+),and EPC(CD34+CD133+KDR+)subsets.The primary outcome was 28-day all-cause death,and secondary outcomes included 7 days rebleeding,90-day death and ICU stay.Multivariate logistic regression analyzed factors associated with 28-day all-cause death,and receiver operating characteristic curve analysis evaluated model discrimination.RESULTS Twenty-nine(20.71%)patients died within 28 days and 29(20.71%)experienced rebleeding within 7 days.Patients in the death group were more critically ill,manifested as higher Sequential Organ Failure Assessment score(10.21±2.15 vs 7.96±3.00,P=0.001),AIMS65 score[4.00(3.00,4.00)vs 3.00(2.00,3.00),P=0.008],proportion of cirrhosis[18(62.07%)vs 27(24.32%),P<0.001],and lactic acid levels[4.20(3.05,5.35)mmol/L vs 2.95(2.28,3.55)mmol/L,P=0.003].Among the circulating progenitor cells,lnEPC(CD34+KDR+)levels were significantly lower in the death group[0.85(0.65,1.15)vs 1.35(1.08,1.60),P<0.001].After adjusting for Sequential Organ Failure Assessment score,lactic acid level,AIMS65 score,and cirrhosis,lnEPCs(CD34+KDR+)remained associated with 28-day mortality(odds ratio=0.557,95%confidence interval:0.353-0.879,P=0.012).The combined model showed moderate discrimination(area under the curve=0.727);at the optimal predicted-probability cutoff of 0.360,the sensitivity and specificity were 0.483 and 0.937,respectively,with acceptable calibration on the Hosmer-Lemeshow test(P=0.622).CONCLUSION A lower early EPC(CD34+KDR+)level was associated with increased short-term mortality in critically ill patients with GIB.The combined EPC-clinical model may complement organ dysfunction assessment and aid supplementary risk stratification.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
摘要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.
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)。
摘要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 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).
摘要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.
基金supported by the National Natural Science Foundation of China(No.U22B6003 and No.52274010)the China Scholarship Council(No.202008080235)。
摘要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.
摘要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 neoplasticumor 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 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.
摘要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.
基金supported by the National Natural Science Foundation of China(Grant No.51977046)Wuxi University Research Start-up Fund for Introduced Talent(2022r021).
摘要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 National Natural Science Foundation of China,No.82270942.
摘要BACKGROUND Diabetic kidney disease(DKD)has become the leading cause of end-stage renal disease.The disease characteristics,morbidity,and renal function progression rate of patients with DKD are all related to sex.This suggests that sex hormones may play an important role in changing renal function in patients with diabetes.There have been only a few studies on the correlation between sex hormones and DKD,which have contradictory conclusions.AIM To investigate the relationship between circulating sex hormone levels and DKD in men and postmenopausal women with type 2 diabetes mellitus(T2DM).METHODS This retrospective cross-sectional study included 356 patients with T2DM.Pearson or Spearman rank correlation analyses assessed the relationships between sex hormone levels and renal function indices.By adjusting for age,body mass index,systolic blood pressure,diastolic blood pressure,duration of diabetes,use of sodium-glucose cotrasporter-2 inhibitor,use of glucagon-like peptide-1 receptor agonist,hypertension,use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor,diabetic retinopathy,diabetic peripheral vascular disease,triglyceride,uric acid,and hemoglobin A1c,multiple linear regression and logistic regression analyses were conducted to identify factors influencing the urinary albumin/creatinine ratio(UACR)and DKD.RESULTS In men,dehydroepiandrosterone sulfate levels were inversely associated with log-transformed UACR after adjustment for covariate factors[regression coefficient(β)=-0.691,95%confidence interval(CI):-1.241 to-0.141 for quartile 4 vs quartile 1;P=0.006 for trend].Elevated levels of estradiol were positively associated with DKD[odds ratio(OR)=3.097,95%CI:1.083-8.856 for quartile 4 vs quartile 1;P=0.041 for trend],and higher luteinizing hormone(LH)levels were similarly associated with DKD(OR=4.164,95%CI:1.30-13.330 for quartile 4 vs quartile 1;P=0.048 for trend).In postmenopausal women,LH levels were positively correlated with log-transformed UACR and DKD(β=1.039,95%CI:0.284-1.794 for quartile 4 vs quartile 1;P=0.006 for trend and OR=15.117,95%CI:2.191-104.326 for quartile 4 vs quartile 1;P=0.004 for trend).Follicle-stimulating hormone(FSH)levels were also positively associated with DKD(OR=9.588,95%CI:1.680-54.709 for quartile 4 vs quartile 1;P=0.014 for trend).CONCLUSION In men with T2DM,elevated levels of estradiol and LH levels were positively associated with increased risk of DKD.In postmenopausal women with T2DM,high FSH and LH levels were positively associated with increased risk of DKD.