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
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
In this paper,we present a necessary and sufficient condition for hyponormal block Toeplitz operators T on the vector-valued weighted Bergman space with symbolsΦ(z)=G^(*)(z)+F(z),where F(z)=∑^(N)_(i)=1 A_(i)z^(i)and...In this paper,we present a necessary and sufficient condition for hyponormal block Toeplitz operators T on the vector-valued weighted Bergman space with symbolsΦ(z)=G^(*)(z)+F(z),where F(z)=∑^(N)_(i)=1 A_(i)z^(i)and G(z)=∑^(N)_(i)=1 A_(−i)z^(i),A_(i)ae culants.展开更多
Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both g...Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both global and regional climates.This study assesses the performance of models participating in phase 6 of the Coupled Model Intercomparison Project in simulating interannual variability modes of Northern Hemisphere 500-hPa geopotential height during winter and summer,distinguishing predictable(potentially predictable on seasonal or longer timescales)and unpredictable(intraseasonal and essentially unpredictable at long range)components,using reanalysis data and a variance decomposition method.Although most models effectively capture unpredictable modes in reanalysis,their ability to reproduce dominant predictable modes-specifically the Pacific-North American pattern,Arctic Oscillation,and Western Pacific Oscillation in winter,and the East Atlantic and North Atlantic Oscillations in summer-varies notably.An optimal ensemble is identified to distinguish(a)predictable-external modes,dominated by external forcing,and(b)predictable-internal modes,associated with slow internal variability,during the historical period(1950-2014)and the SSP5-8.5 scenario(2036-2100).Under increased radiative forcing,the leading winter/summer predictable-external mode exhibits a more uniform spatial distribution,remarkably larger trend and annual variance,and enhanced height-sea surface temperature(SST)covariance under SSP5-8.5 compared to historical conditions.The dominant winter/summer predictable-internal modes also exhibit increased variance and height-SST covariance under SSP5-8.5,along with localized changes in spatial configuration.Minimal changes are observed in spatial distribution or variance for dominant winter/summer unpredictable modes under SSP5-8.5.This study,from a predictive perspective,deepens our understanding of model uncertainties and projected changes in circulations.展开更多
Wind-induced circulation is the main form of lake flow for shallow lakes and plays an important role in algae population distribution.This study constructed a three-dimensional hydrodynamic model(EFDC)of the plateau l...Wind-induced circulation is the main form of lake flow for shallow lakes and plays an important role in algae population distribution.This study constructed a three-dimensional hydrodynamic model(EFDC)of the plateau lake Erhai,China using accuracy wind field observation,runoff data and monthly algae data during 2022–2023.The model successfully reproduced the circulation characteristics of Erhai under prevailing wind directions.The results showed that the lake flow velocity in Lake Erhai is higher in winter than in summer,with lower velocities near shore particularly in the northern and central parts of the lake.There is a negative correlation between algal biomass and flow velocity(FV)in different zones,with lower FV favoring the accumulation of algal biomass,particularly for Microcystis,Dolichospermum,and Peridinium.Additionally,due to buoyancy,cyanobacteria are highly affected by wind direction and tend to accumulate in downwind regions of the prevailing wind direction.This study demonstrates that wind-induced circulation is a crucial factor affecting the spatial distribution of dominant algae populations in shallow plateau lakes with weak hydrodynamic force.Further,the risk of bloom occurrence in Lake Erhai will be higher due to the background of global climate change and the lake’s wind speed decline.In conclusion,we suggest implementing targeted zoning measures to control algal blooms and establishing stricter regulations for nitrogen and phosphorus control to counterbalance the promotion of algal bloom accumulation in low-velocity zones caused by reduced wind speed.展开更多
Clouds play an important role in global atmospheric energy and water vapor budgets, and the low cloud simulations suffer from large biases in many atmospheric general circulation models. In this study, cloud microphys...Clouds play an important role in global atmospheric energy and water vapor budgets, and the low cloud simulations suffer from large biases in many atmospheric general circulation models. In this study, cloud microphysical processes such as raindrop evaporation and cloud water accretion in a double-moment six-class cloud microphysics scheme were revised to enhance the simulation of low clouds using the Global-Regional Integrated Forecast System(GRIST)model. The validation of the revised scheme using a single-column version of the GRIST demonstrated a reasonable reduction in liquid water biases. The revised parameterization simulated medium-and low-level cloud fractions that were in better agreement with the observations than the original scheme. Long-term global simulations indicate the mitigation of the originally overestimated low-level cloud fraction and cloud-water mixing ratio in mid-to high-latitude regions,primarily owing to enhanced accretion processes and weakened raindrop evaporation. The reduced low clouds with the revised scheme showed better consistency with satellite observations, particularly at mid-and high-latitudes. Further improvements can be observed in the simulated cloud shortwave radiative forcing and vertical distribution of total cloud cover. Annual precipitation in mid-latitude regions has also improved, particularly over the oceans, with significantly increased large-scale and decreased convective precipitation.展开更多
To solve the problem of circulating power of dual active bridge(DAB)DC-DC converter over a wide voltage conversion ratio,this paper proposes a novel synchronous PWM(S-PWM)modulation.Existence of circulating power incr...To solve the problem of circulating power of dual active bridge(DAB)DC-DC converter over a wide voltage conversion ratio,this paper proposes a novel synchronous PWM(S-PWM)modulation.Existence of circulating power increases current stress of devices and decreases efficiency,especially under light load conditions.Several modulation methods have been proposed to overcome the problem.They can reduce or eliminate either input or output side circulating power.In contrast,S-PWM not only eliminates both sides circulating power and reduces current stress,but also achieves zero-current-switching(ZCS)turn-on for all switches and ZCS turn-off for most across the full power range.No auxiliary or snubber circuits are increased.In addition,the control can be simplified so the transmitted power is related to only one variable.The S-PWM has four cases under different gain and power conditions.The detailed operation principle and modes of DAB under S-PWM are analyzed in the paper.In addition,four modulations in literature are discussed,and corresponding comparative analyses with S-PWM are given.Finally,a laboratory prototype is built to verify advantages and effectiveness of the proposed modulation.展开更多
The present study compares the Atlantic Meridional Overturning Circulation(AMOC)in the North Atlantic from two simulations by an oceanic general circulation model with 1°×1°and 0.1°×0.1°r...The present study compares the Atlantic Meridional Overturning Circulation(AMOC)in the North Atlantic from two simulations by an oceanic general circulation model with 1°×1°and 0.1°×0.1°resolution,respectively,which explores the sensitivity of AMOC to the resolution.The ocean model is the latest version of the LASG/IAP Climate System Model(LICOM3),and it is forced with atmospheric data from phase 2 of the Ocean Model Intercomparison Project(OMIP2).Comprehensive comparison between the two simulations indicates that the simulated AMOC is highly sensitive to the spatial resolution.The high-resolution model(LICOM-H)simulates a deeper mixed-layer depth(MLD),due to increased surface salinity,than that in the low-resolution model(LICOML)in the Labrador Sea,and it also has stronger AMOC strength(the maximum climatic mean AMOC from 1958 to 2018 is 23.4 Sv for LICOM-H and 21.2 Sv for LICOM-L)and larger variability of AMOC index(2.3 Sv for LICOM-H and 1.7 Sv for LICOM-L).These differences can mainly be attributed to two main dynamic processes that benefit from high resolution.Firstly,LICOM-H can simulate much stronger boundary currents(~0.6 m s^(-1))than LICOM-L(0.3 m s^(-1))in the upper ocean,which leads to saltier and warmer seawater being transported to the Labrador Sea,where it enhances deep convection.Secondly,in LICOM-H,the stronger variability of AMOC is related to the higher sensitivity of the MLD and transformation to the prescribed atmospheric forcing in the Labrador Sea.展开更多
Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to t...Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.展开更多
High-sulfur iron concentrates emit SO_(2)into the flue gas during pellet induration.To investigate the effect of the SO_(2)cycle on pellet quality in the grate-kiln process,sulfur balance analysis,thermodynamic calcul...High-sulfur iron concentrates emit SO_(2)into the flue gas during pellet induration.To investigate the effect of the SO_(2)cycle on pellet quality in the grate-kiln process,sulfur balance analysis,thermodynamic calculations,and pellet production experiments under simulated flue gas circulation conditions were conducted.The results indicated that SO_(2)circulation inhibited desulfurization and deteriorated pellet strength.SO_(2)absorption increased the pellet sulfur content to 0.70 wt.%during the downdraft drying phase,and the absorption could be aggravated by the moisture.The desulfurization rate of the preheating process was also decreased to 16.67%,resulting from the refractory sulfate generation.Sulfur content of the roasted pellets dropped to 0.13 wt.%because of the aluminosilicate generation.The finished pellet sulfur content further decreased to 0.08 wt.%due to the fresh air during the cooling process.Eventually,optimization measures were proposed when high-sulfur iron concentrates were used for oxidized pellet preparation.展开更多
Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in...Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).展开更多
By reviewing the mechanisms of drilling fluid lost circulation and its control in fractured formations, the applicability and working mechanisms of different kinds of lost circulation materials in plugging fractured f...By reviewing the mechanisms of drilling fluid lost circulation and its control in fractured formations, the applicability and working mechanisms of different kinds of lost circulation materials in plugging fractured formations have been summarized. Meanwhile, based on the types of lost circulation materials, the advantages, disadvantages, and application effects of corresponding plugging technologies have been analyzed to sort out the key problems existing in the current lost circulation control technologies. On this basis, the development direction of plugging technology for severe loss have been pointed out. It is suggested that that the lost circulation control technology should combine different disciplines such as geology, engineering and materials to realize integration, intelligence and systematization in the future. Five research aspects should be focused on:(1) the study on mechanisms of drilling fluid lost circulation and its control to provide basis for scientific selection of lost circulation material formulas, control methods and processes;(2) the research and development of self-adaptive lost circulation materials to improve the matching relationship between lost control materials and fracture scales;(3) the research and development of lost circulation materials with strong retention and strong filling in three-dimensional fracture space, to enhance the retention and filling capacities of materials in fractures and improve the lost circulation control effect;(4) the research and development of lost circulation materials with high temperature tolerance, to ensure the long-term plugging effect of deep high-temperature formations;(5) the study on digital and intelligent lost circulation control technology, to promote the development of lost circulation control technology to digital and intelligent direction.展开更多
During drilling operations in deep fractured tight gas reservoirs,lost circulation of working fluid frequently occurs due to the formationʼs low pressure-bearing capacity.Adding lost circulation materials(LCMs)to dril...During drilling operations in deep fractured tight gas reservoirs,lost circulation of working fluid frequently occurs due to the formationʼs low pressure-bearing capacity.Adding lost circulation materials(LCMs)to drilling fluids is the most common method for controlling lost circulation.Among these,granular LCMs are widely used,but the application frequency of flaky LCMs has been increasing annually due to their unique morphology.However,the migration and plugging behavior of flaky LCMs within fractures,and the mechanisms enhancing the pressure-bearing capacity of the plugging zone are not well understood.Therefore,this study conducted visual plugging experiments and dynamic fracture plugging experiments to evaluate the plugging mode and pressure-bearing capacity of the plugging slurry with various particle sizes and concentrations of flaky LCMs.The experimental results demonstrate that the fracture plugging process can be divided into four stages:uniform flow stage of the plugging slurry,formation and development stage of the bridging area,formation and development stage of the plugging area,and pressure-bearing stage of the plugging zone.The inclusion of flaky LCMs notably reduces the duration of stages 1 and 2,while simultaneously increasing the proportion of the plugging zone and enhancing its surface porosity.Flaky LCMs reduce the effective fracture width through“interception”and“co-bridging”modes,thus improving plugging zone formation efficiency.Appropriate particle size and concentration of flaky LCMs increase the area and length of the plugging zone.This reduces the fracture width increment caused by injection pressure and enhances frictional force between the plugging zone and fracture surface,thereby improving the pressure-bearing capacity of the plugging zone.However,excessively high concentrations of flaky LCMs result in decreased structural stability of the plugging zone,and excessively large particle sizes increase the risk of plugging outside fracture inlet.The recommended concentration of flaky LCMs in the plugging slurry is 2%–3%,with a particle size 1.2 to 1.5 times that of the bridging granular LCMs and not exceeding twice the fracture width.This study provides a theoretical foundation for selecting LCMs and designing plugging formulations for field applications.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
Lost circulation of drilling fluid is an international engineering problem during drilling.Aiming at the problems of the first-time lost circulation control success rate and poor adaptability of traditional lost circu...Lost circulation of drilling fluid is an international engineering problem during drilling.Aiming at the problems of the first-time lost circulation control success rate and poor adaptability of traditional lost circulation materials,a new self-healing lost circulation material based on dynamic disulfide bonds was prepared and named CKSH.In this paper,the particle size of self-healing lost circulation material was from 0.1 to 5 mm.The structure was analyzed by modern characterization means,and the drilling fluid compatibility,self-healing performance were evaluated.The self-healing and bridging-filling-sealing mechanism of CKSH were revealed.The results showed that the healing rate of CKSH could reach100%after 12 h over 70℃.It showed good compatibility with drilling fluid,with no effect on rheology or filtration loss.It could be stably suspended in drilling fluid,and the temperature resistance reached140℃.Healing by self-healing lost circulation materials of different particle size,the pressure bearing capacity of plugging zone were over 12 MPa for fracture opening of 1–5 mm.It could play a synergistic role with traditional lost circulation materials by chemical bonding,and the repeated loss caused by physical plugging was avoided.The research results of this paper can improve the bridging plugging bearing pressure strength and the first-time lost circulation control success rate,which is of great significance for improving drilling efficiency and reducing non-productive time.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
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
The movement of global ocean circulation in the Earth’s main magnetic field generates a measurable induced magnetic field(about 2 nT at geomagnetic satellite altitudes).However,this ocean circulation-induced magnetic...The movement of global ocean circulation in the Earth’s main magnetic field generates a measurable induced magnetic field(about 2 nT at geomagnetic satellite altitudes).However,this ocean circulation-induced magnetic field has not been previously estimated or incorporated into geomagnetic field models,potentially causing leakage into the core field model.Here,we present a method to account for the circulation-induced magnetic field during geomagnetic field modeling.First,a forward model of the circulation-induced magnetic field is constructed by numerically solving electromagnetic induction equations based on a realistic ocean circulation model.Then,this forward model is subtracted from the observed data.Finally,the core and lithospheric fields,magnetospheric and Earth’s mantle-induced fields,and the ocean tide-induced magnetic field are co-estimated.Applying our method to over 20 years of MSS-1,Swarm,CryoSat-2,and CHAMP satellite magnetic data,we derive a new multisource geomagnetic field model(MGFM).We find that incorporating a forward model of the circulation-induced magnetic field marginally improves the fit to the data.Furthermore,we demonstrate that neglecting the circulation-induced magnetic field in geomagnetic field modeling results in leakage into the core field model.The highlights of the MGFM model include:(i)a good agreement with the widely used CHAOS model series;(ii)the incorporation of magnetic fields induced by both ocean tides and circulation;and(iii)the suppression of leakage of the circulation-induced magnetic field into the core field model.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
基金funded by Sapienza University PNRR-RT_SPOKE_1—ROME TECHNOPOLE—Spoke 1—B83C22002820006—ECS00000024 and FO R.O.onlus.
文摘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)。
文摘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.
文摘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.
文摘In this paper,we present a necessary and sufficient condition for hyponormal block Toeplitz operators T on the vector-valued weighted Bergman space with symbolsΦ(z)=G^(*)(z)+F(z),where F(z)=∑^(N)_(i)=1 A_(i)z^(i)and G(z)=∑^(N)_(i)=1 A_(−i)z^(i),A_(i)ae culants.
基金supported by the National Natural Science Foundation of China(Grant Nos.U2342210 and 42275043)the National Institute of Natural Hazards,Ministry of Emergency Management of China(Grant Nos.J2223806,ZDJ2024-25 and ZDJ2025-34)。
文摘Climate models are essential for understanding past,present,and future changes in atmospheric circulation,with circulation modes providing key sources of seasonal predictability and prediction uncertainties for both global and regional climates.This study assesses the performance of models participating in phase 6 of the Coupled Model Intercomparison Project in simulating interannual variability modes of Northern Hemisphere 500-hPa geopotential height during winter and summer,distinguishing predictable(potentially predictable on seasonal or longer timescales)and unpredictable(intraseasonal and essentially unpredictable at long range)components,using reanalysis data and a variance decomposition method.Although most models effectively capture unpredictable modes in reanalysis,their ability to reproduce dominant predictable modes-specifically the Pacific-North American pattern,Arctic Oscillation,and Western Pacific Oscillation in winter,and the East Atlantic and North Atlantic Oscillations in summer-varies notably.An optimal ensemble is identified to distinguish(a)predictable-external modes,dominated by external forcing,and(b)predictable-internal modes,associated with slow internal variability,during the historical period(1950-2014)and the SSP5-8.5 scenario(2036-2100).Under increased radiative forcing,the leading winter/summer predictable-external mode exhibits a more uniform spatial distribution,remarkably larger trend and annual variance,and enhanced height-sea surface temperature(SST)covariance under SSP5-8.5 compared to historical conditions.The dominant winter/summer predictable-internal modes also exhibit increased variance and height-SST covariance under SSP5-8.5,along with localized changes in spatial configuration.Minimal changes are observed in spatial distribution or variance for dominant winter/summer unpredictable modes under SSP5-8.5.This study,from a predictive perspective,deepens our understanding of model uncertainties and projected changes in circulations.
基金supported by the Open Research Fund of Key Laboratory for Lake Pollution Control of the Ministry of Ecology and Environment(No.2024HPYKFZD04)the Fundamental Research Funds for the Central Publicinterest Scientific Institution(No.2025YSKY-04)the National Natural Science Foundation of China(Nos.U1902207 and 42207265).
文摘Wind-induced circulation is the main form of lake flow for shallow lakes and plays an important role in algae population distribution.This study constructed a three-dimensional hydrodynamic model(EFDC)of the plateau lake Erhai,China using accuracy wind field observation,runoff data and monthly algae data during 2022–2023.The model successfully reproduced the circulation characteristics of Erhai under prevailing wind directions.The results showed that the lake flow velocity in Lake Erhai is higher in winter than in summer,with lower velocities near shore particularly in the northern and central parts of the lake.There is a negative correlation between algal biomass and flow velocity(FV)in different zones,with lower FV favoring the accumulation of algal biomass,particularly for Microcystis,Dolichospermum,and Peridinium.Additionally,due to buoyancy,cyanobacteria are highly affected by wind direction and tend to accumulate in downwind regions of the prevailing wind direction.This study demonstrates that wind-induced circulation is a crucial factor affecting the spatial distribution of dominant algae populations in shallow plateau lakes with weak hydrodynamic force.Further,the risk of bloom occurrence in Lake Erhai will be higher due to the background of global climate change and the lake’s wind speed decline.In conclusion,we suggest implementing targeted zoning measures to control algal blooms and establishing stricter regulations for nitrogen and phosphorus control to counterbalance the promotion of algal bloom accumulation in low-velocity zones caused by reduced wind speed.
基金National Natural Science Foundation of China(42375153,42105153,42205157)Development of Science and Technology at Chinese Academy of Meteorological Sciences(2023KJ038)。
文摘Clouds play an important role in global atmospheric energy and water vapor budgets, and the low cloud simulations suffer from large biases in many atmospheric general circulation models. In this study, cloud microphysical processes such as raindrop evaporation and cloud water accretion in a double-moment six-class cloud microphysics scheme were revised to enhance the simulation of low clouds using the Global-Regional Integrated Forecast System(GRIST)model. The validation of the revised scheme using a single-column version of the GRIST demonstrated a reasonable reduction in liquid water biases. The revised parameterization simulated medium-and low-level cloud fractions that were in better agreement with the observations than the original scheme. Long-term global simulations indicate the mitigation of the originally overestimated low-level cloud fraction and cloud-water mixing ratio in mid-to high-latitude regions,primarily owing to enhanced accretion processes and weakened raindrop evaporation. The reduced low clouds with the revised scheme showed better consistency with satellite observations, particularly at mid-and high-latitudes. Further improvements can be observed in the simulated cloud shortwave radiative forcing and vertical distribution of total cloud cover. Annual precipitation in mid-latitude regions has also improved, particularly over the oceans, with significantly increased large-scale and decreased convective precipitation.
文摘To solve the problem of circulating power of dual active bridge(DAB)DC-DC converter over a wide voltage conversion ratio,this paper proposes a novel synchronous PWM(S-PWM)modulation.Existence of circulating power increases current stress of devices and decreases efficiency,especially under light load conditions.Several modulation methods have been proposed to overcome the problem.They can reduce or eliminate either input or output side circulating power.In contrast,S-PWM not only eliminates both sides circulating power and reduces current stress,but also achieves zero-current-switching(ZCS)turn-on for all switches and ZCS turn-off for most across the full power range.No auxiliary or snubber circuits are increased.In addition,the control can be simplified so the transmitted power is related to only one variable.The S-PWM has four cases under different gain and power conditions.The detailed operation principle and modes of DAB under S-PWM are analyzed in the paper.In addition,four modulations in literature are discussed,and corresponding comparative analyses with S-PWM are given.Finally,a laboratory prototype is built to verify advantages and effectiveness of the proposed modulation.
基金supported by the National Natural Science Foundation of China [grant number 92358302]。
文摘The present study compares the Atlantic Meridional Overturning Circulation(AMOC)in the North Atlantic from two simulations by an oceanic general circulation model with 1°×1°and 0.1°×0.1°resolution,respectively,which explores the sensitivity of AMOC to the resolution.The ocean model is the latest version of the LASG/IAP Climate System Model(LICOM3),and it is forced with atmospheric data from phase 2 of the Ocean Model Intercomparison Project(OMIP2).Comprehensive comparison between the two simulations indicates that the simulated AMOC is highly sensitive to the spatial resolution.The high-resolution model(LICOM-H)simulates a deeper mixed-layer depth(MLD),due to increased surface salinity,than that in the low-resolution model(LICOML)in the Labrador Sea,and it also has stronger AMOC strength(the maximum climatic mean AMOC from 1958 to 2018 is 23.4 Sv for LICOM-H and 21.2 Sv for LICOM-L)and larger variability of AMOC index(2.3 Sv for LICOM-H and 1.7 Sv for LICOM-L).These differences can mainly be attributed to two main dynamic processes that benefit from high resolution.Firstly,LICOM-H can simulate much stronger boundary currents(~0.6 m s^(-1))than LICOM-L(0.3 m s^(-1))in the upper ocean,which leads to saltier and warmer seawater being transported to the Labrador Sea,where it enhances deep convection.Secondly,in LICOM-H,the stronger variability of AMOC is related to the higher sensitivity of the MLD and transformation to the prescribed atmospheric forcing in the Labrador Sea.
基金supported by the National Natural Science Foundation of China(Grant No.42275041)the Hainan Province Science and Technology Special Fund(Grant No.SOLZSKY2025006).
文摘Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.
基金supported by the Science and Technology Innovation Program of Hunan Province(Nos.2023RC1025 and 2024RC3022)the Technology Special Program Project of China Minmetals Corporation(No.2021ZXA04)the Major Scientific Research Projects of Inner Mongolia Baotou Steel Union Co.,Ltd.(No.HKF202300356).
文摘High-sulfur iron concentrates emit SO_(2)into the flue gas during pellet induration.To investigate the effect of the SO_(2)cycle on pellet quality in the grate-kiln process,sulfur balance analysis,thermodynamic calculations,and pellet production experiments under simulated flue gas circulation conditions were conducted.The results indicated that SO_(2)circulation inhibited desulfurization and deteriorated pellet strength.SO_(2)absorption increased the pellet sulfur content to 0.70 wt.%during the downdraft drying phase,and the absorption could be aggravated by the moisture.The desulfurization rate of the preheating process was also decreased to 16.67%,resulting from the refractory sulfate generation.Sulfur content of the roasted pellets dropped to 0.13 wt.%because of the aluminosilicate generation.The finished pellet sulfur content further decreased to 0.08 wt.%due to the fresh air during the cooling process.Eventually,optimization measures were proposed when high-sulfur iron concentrates were used for oxidized pellet preparation.
基金supported by the National Key Research and Development Program of China (2021YFD1800200)the National Natural Science Foundation of China (32170539)。
文摘Influenza A virus(IAV) has a wide host range,including wild birds,poultry,various mammals,and even humans(Xu et al.2024).Currently,two subtypes of canine influenza virus(CIV),H3N8 and H3N2,are primarily circulating in dogs.The H3N8 CIV was introduced from horses into dogs in 2004(Crawford et al.2005),while the H3N2 CIV originated from chickens in Asia in 2007(Song et al.2008).In China,H3N2 is the predominant CIV subtype,with a prevalence rate of up to 5.63% in the canine population,as reported by Chen et al.(2023).CIV infection typically manifests with symptoms such as coughing,sneezing,runny nose,and fever but is rarely fatal.However,co-infection with other pathogens(e.g.,Streptococcus,Mycoplasma or canine parainfluenza virus) can exacerbate symptoms and lead to lethal outcomes(Yondo et al.2023).
基金Supported by National Natural Science Foundation of China(51991361,52074327,U1762212)Major Engineering Technology Field Tes Project of CNPC(2020F-45)。
文摘By reviewing the mechanisms of drilling fluid lost circulation and its control in fractured formations, the applicability and working mechanisms of different kinds of lost circulation materials in plugging fractured formations have been summarized. Meanwhile, based on the types of lost circulation materials, the advantages, disadvantages, and application effects of corresponding plugging technologies have been analyzed to sort out the key problems existing in the current lost circulation control technologies. On this basis, the development direction of plugging technology for severe loss have been pointed out. It is suggested that that the lost circulation control technology should combine different disciplines such as geology, engineering and materials to realize integration, intelligence and systematization in the future. Five research aspects should be focused on:(1) the study on mechanisms of drilling fluid lost circulation and its control to provide basis for scientific selection of lost circulation material formulas, control methods and processes;(2) the research and development of self-adaptive lost circulation materials to improve the matching relationship between lost control materials and fracture scales;(3) the research and development of lost circulation materials with strong retention and strong filling in three-dimensional fracture space, to enhance the retention and filling capacities of materials in fractures and improve the lost circulation control effect;(4) the research and development of lost circulation materials with high temperature tolerance, to ensure the long-term plugging effect of deep high-temperature formations;(5) the study on digital and intelligent lost circulation control technology, to promote the development of lost circulation control technology to digital and intelligent direction.
基金support from the National Natural Science Foundation of China(Grant No.52274009).
文摘During drilling operations in deep fractured tight gas reservoirs,lost circulation of working fluid frequently occurs due to the formationʼs low pressure-bearing capacity.Adding lost circulation materials(LCMs)to drilling fluids is the most common method for controlling lost circulation.Among these,granular LCMs are widely used,but the application frequency of flaky LCMs has been increasing annually due to their unique morphology.However,the migration and plugging behavior of flaky LCMs within fractures,and the mechanisms enhancing the pressure-bearing capacity of the plugging zone are not well understood.Therefore,this study conducted visual plugging experiments and dynamic fracture plugging experiments to evaluate the plugging mode and pressure-bearing capacity of the plugging slurry with various particle sizes and concentrations of flaky LCMs.The experimental results demonstrate that the fracture plugging process can be divided into four stages:uniform flow stage of the plugging slurry,formation and development stage of the bridging area,formation and development stage of the plugging area,and pressure-bearing stage of the plugging zone.The inclusion of flaky LCMs notably reduces the duration of stages 1 and 2,while simultaneously increasing the proportion of the plugging zone and enhancing its surface porosity.Flaky LCMs reduce the effective fracture width through“interception”and“co-bridging”modes,thus improving plugging zone formation efficiency.Appropriate particle size and concentration of flaky LCMs increase the area and length of the plugging zone.This reduces the fracture width increment caused by injection pressure and enhances frictional force between the plugging zone and fracture surface,thereby improving the pressure-bearing capacity of the plugging zone.However,excessively high concentrations of flaky LCMs result in decreased structural stability of the plugging zone,and excessively large particle sizes increase the risk of plugging outside fracture inlet.The recommended concentration of flaky LCMs in the plugging slurry is 2%–3%,with a particle size 1.2 to 1.5 times that of the bridging granular LCMs and not exceeding twice the fracture width.This study provides a theoretical foundation for selecting LCMs and designing plugging formulations for field applications.
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.
基金supported by National Natural Science Foundation of China(52304006,52274032,and 51774062)the General Project of the Chongqing Natural Science Foundation(CSTB2022NSCQ-MSX1554 and CSTB2022NSCQ-MSX0349)Shaanxi Province Key Laboratory of Environmental Pollution Control and Reservoir Protection Technology of Oilfields and Engineering Research Center of Oil and Gas Field Chemistry,Universities of Shaanxi Province(XSYU-CCCE-2402).
文摘Lost circulation of drilling fluid is an international engineering problem during drilling.Aiming at the problems of the first-time lost circulation control success rate and poor adaptability of traditional lost circulation materials,a new self-healing lost circulation material based on dynamic disulfide bonds was prepared and named CKSH.In this paper,the particle size of self-healing lost circulation material was from 0.1 to 5 mm.The structure was analyzed by modern characterization means,and the drilling fluid compatibility,self-healing performance were evaluated.The self-healing and bridging-filling-sealing mechanism of CKSH were revealed.The results showed that the healing rate of CKSH could reach100%after 12 h over 70℃.It showed good compatibility with drilling fluid,with no effect on rheology or filtration loss.It could be stably suspended in drilling fluid,and the temperature resistance reached140℃.Healing by self-healing lost circulation materials of different particle size,the pressure bearing capacity of plugging zone were over 12 MPa for fracture opening of 1–5 mm.It could play a synergistic role with traditional lost circulation materials by chemical bonding,and the repeated loss caused by physical plugging was avoided.The research results of this paper can improve the bridging plugging bearing pressure strength and the first-time lost circulation control success rate,which is of great significance for improving drilling efficiency and reducing non-productive time.
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.
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 Natural Science Foundation of China(42250101,42250102)the Macao Foundation.
文摘The movement of global ocean circulation in the Earth’s main magnetic field generates a measurable induced magnetic field(about 2 nT at geomagnetic satellite altitudes).However,this ocean circulation-induced magnetic field has not been previously estimated or incorporated into geomagnetic field models,potentially causing leakage into the core field model.Here,we present a method to account for the circulation-induced magnetic field during geomagnetic field modeling.First,a forward model of the circulation-induced magnetic field is constructed by numerically solving electromagnetic induction equations based on a realistic ocean circulation model.Then,this forward model is subtracted from the observed data.Finally,the core and lithospheric fields,magnetospheric and Earth’s mantle-induced fields,and the ocean tide-induced magnetic field are co-estimated.Applying our method to over 20 years of MSS-1,Swarm,CryoSat-2,and CHAMP satellite magnetic data,we derive a new multisource geomagnetic field model(MGFM).We find that incorporating a forward model of the circulation-induced magnetic field marginally improves the fit to the data.Furthermore,we demonstrate that neglecting the circulation-induced magnetic field in geomagnetic field modeling results in leakage into the core field model.The highlights of the MGFM model include:(i)a good agreement with the widely used CHAOS model series;(ii)the incorporation of magnetic fields induced by both ocean tides and circulation;and(iii)the suppression of leakage of the circulation-induced magnetic field into the core field model.
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.
