Circulating tumor DNA in liquid biopsy: Current diagnostic limitation

With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision medicine.cfDNA is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic cells.Tumor cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of cancer.In this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the future.Although the future faces major challenges,it also con-tains great potential.

Experimental study on secondary air mixing along the bed height in a circulating fluidized bed with a multitracer-gas method

A multitracer-gas method was proposed to study the secondary air(SA)mixing along the bed height in a circulating fluidized bed(CFB)using carbon monoxide(CO),oxygen(O_(2)),and carbon dioxide(CO_(2))as tracer gases.Experiments were carried out on a cold CFB test rig with a cross-section of 0.42 m×0.73 m and a height of 5.50 m.The effects of superficial velocity,SA ratio,bed inventory,and particle diameter on the SA mixing were investigated.The results indicate that there are some differences in the measurement results obtained using different tracer gases,wherein the deviation between CO and CO_(2) ranges from 42%to 66%and that between O_(2) and CO_(2) ranges from 45%to 71%in the lower part of the fluidized bed.However,these differences became less pronounced as the bed height increased.Besides,the high solid concentration and fine particle diameter in the CFB may weaken the difference.The measurement results of different tracer gases show the same trends under the variation of operating parameters.Increasing superficial velocity and SA ratio and decreasing particle diameter result in better mixing of the SA.The effect of bed inventory on SA mixing is not monotonic.

Long-term operation optimization of circulating cooling water systems under fouling conditions

Fouling caused by excess metal ions in hard water can negatively impact the performance of the circulating cooling water system(CCWS)by depositing ions on the heat exchanger's surface.Currently,the operation optimization of CCWS often prioritizes short-term flow velocity optimization for minimizing power consumption,without considering fouling.However,low flow velocity promotes fouling.Therefore,it's crucial to balance fouling and energy/water conservation for optimal CCWS long-term operation.This study proposes a mixed-integer nonlinear programming(MINLP)model to achieve this goal.The model considers fouling in the pipeline,dynamic concentration cycle,and variable frequency drive to optimize the synergy between heat transfer,pressure drop,and fouling.By optimizing the concentration cycle of the CCWS,water conservation and fouling control can be achieved.The model can obtain the optimal operating parameters for different operation intervals,including the number of pumps,frequency,and valve local resistance coefficient.Sensitivity experiments on cycle and environmental temperature reveal that as the cycle increases,the marginal benefits of energy/water conservation decrease.In periods with minimal impact on fouling rate,energy/water conservation can be achieved by increasing the cycle while maintaining a low fouling rate.Overall,the proposed model has significant energy/water saving effects and can comprehensively optimize the CCWS through its incorporation of fouling and cycle optimization.

Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers;the most prominent is circulating tumor DNA(ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction(PCR) [emulsion PCR(ePCR), digital PCR(dPCR), and bead, emulsion, amplification, magnetic(BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection,treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations(either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1;2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF;3) DNA methylation(RASSF1A, SEPT9, KMT2C and CCNA2);4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1;and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results.Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Particle residence time distribution and axial dispersion coefficient in a pressurized circulating fluidized bed by using multiphase particle-in-cell simulation

The particle residence time distribution(RTD)and axial dispersion coefficient are key parameters for the design and operation of a pressurized circulating fluidized bed(PCFB).In this study,the effects of pressure(0.1-0.6 MPa),fluidizing gas velocity(2-7 m·s^(-1)),and solid circulation rate(10-90 kg·m^(-2)·s^(-1))on particle RTD and axial dispersion coefficient in a PCFB are numerically investigated based on the multiphase particle-in-cell(MP-PIC)method.The details of the gas-solid flow behaviors of PCFB are revealed.Based on the gas-solid flow pattern,the particles tend to move more orderly under elevated pressures.With an increase in either fluidizing gas velocity or solid circulation rate,the mean residence time of particles decreases while the axial dispersion coefficient increases.With an increase in pressure,the core-annulus flow is strengthened,which leads to a wider shape of the particle RTD curve and a larger mean particle residence time.The back-mixing of particles increases with increasing pressure,resulting in an increase in the axial dispersion coefficient.

Causal relationship between circulating vitamin C and 25-hydroxyvitamin D concentrations and common mental disorders-a Mendelian randomization study

Mental disorders seriously affect people’s health and social stability.This Mendelian randomization(MR)study was designed to investigate the causal relationship between circulating vitamin C(VC)or 25-hydroxyvitamin D(25(OH)D)levels and mental disorders.The data used for the MR analysis were derived from the summary genome-wide association studies(GWAS)database for VC and 25(OH)D and from the Finn Gen consortium for fourteen mental disorders.Based on the inverse variance weighted(IVW)method,we found a potential causal association between circulating VC and anxiety disorders(IVW:OR=1.139,95%CI:1.023-1.269,P=0.018).However,no causal association was found between VC or 25(OH)D and other mental disorders(P>0.05).In the reverse MR analysis,individuals with Alzheimer’s disease was causally associated with higher concentrations of circulating VC(P=0.012),while individuals with anxiety disorders had a negative association between the concentrations of 25(OH)D(P=0.012).However,the current evidence does not support a causal relationship between VC or 25(OH)D and other mental disorders.In addition,there was no causal association between circulating VC and 25(OH)D(P>0.05).Future studies are needed to confirm these findings and to elucidate the mechanisms of potential causality.

In vivo fluorescence flow cytometry reveals that the nanoparticle tumor vaccine OVA@HA-PEI effectively clears circulating tumor cells

Tumor vaccine therapy offers significant advantages over conventional treatments,including reduced toxic side effects.However,it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods.Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors,thereby limiting their clinical efficacy.In this study,we developed a nanoparticle-based tumor vaccine,OVA@HA-PEI,utilizing ovalbumin(OVA)as the presenting antigen and hyaluronic acid(HA)and polyethyleneimine(PEI)as adjuvants and carriers.This formulation significantly enhanced the proliferation of immune cells and cytokines,such as CD3,CD8,interferon-,and tumor necrosis factor-,in vivo,effectively activating an immune response against B16–F10 tumors.In vivofluorescenceflow cytometry(IVFC)has already become an effective method for monitoring circulating tumor cells(CTCs)due to its direct,noninvasive,and long-term detection capabilities.Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1(PD-1)antibody.The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone.Additionally,this combination therapy substantially reduced the number of CTCs in vivo,increased the clearance rate of CTCs by the immune system,and slowed tumor progression.Thesefindings greatly enhance the clinical application prospects of IVFC and tumor vaccines.

Simulation of gas-solid flow characteristics of the circulating fluidized bed boiler under pure-oxygen combustion conditions

Under the pressure of carbon neutrality,many carbon capture,utilization and storage technologies have witnessed rapid development in the recent years,including oxy-fuel combustion(OFC)technology.However,the conventional OFC technology usually depends on the flue gas recirculation system,which faces significant investment,high energy consumption,and potential low-temperature corrosion problem.Considering these deficiencies,the direct utilization of pure oxygen to achieve particle fluidization and fuel combustion may reduce the overall energy consumption and CO_(2)-capture costs.In this paper,the fundamental structure of a self-designed 130 t·h^(-1) pure-oxygen combustion circulating fluidized bed(CFB)boiler was provided,and the computational particle fluid dynamics method was used to analyze the gas-solid flow characteristics of this new-concept boiler under different working conditions.The results indicate that through the careful selection of design or operational parameters,such as average bed-material size and fluidization velocity,the pure-oxygen combustion CFB system can maintain the ideal fluidization state,namely significant internal and external particle circulation.Besides,the contraction section of the boiler leads to the particle backflow in the lower furnace,resulting in the particle suspension concentration near the wall region being higher than that in the center region.Conversely,the upper furnace still retains the classic core-annulus flow structure.In addition to increasing solid circulation rate by reducing the average bed-material size,altering primary gas ratio and bed inventory can also exert varying degrees of influence on the gas-solid flow characteristics of the pure-oxygen combustion CFB boiler.

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Circulating tumor cells as prognostic marker in pancreatic cancer

In this editorial we comment on the article by Zhang et al published in the recent issue of the World Journal of Clinical Oncology.Pancreatic cancer is the fourth most common cause of cancer-related mortality and has the lowest survival rate among all solid cancers.It causes 227000 deaths annually worldwide,and the 5-year survival rate is very low due to early metastasis,which is 4.6%.Cancer survival increases with better knowledge of risk factors and early and accurate diagnosis.Circulating tumor cells(CTCs)are tumor cells that intravasate from the primary tumor or metastasis foci into the peripheral blood circulation system spontan-eously or during surgical operations.Detection of CTC in blood is promising for early diagnosis.In addition,studies have associated high CTC levels with a more advanced stage,and more intensive treatments should be considered in cases with high CTC.In tumors that are considered radiologically resectable,it may be of critical importance in detecting occult metastases and preventing unnecessary surgeries.

Circulating tumor cells in pancreatic cancer:The prognostic impact in surgical patients

Pancreatic cancer is associated with a poor prognosis,even in the early stages,mainly due to metastatic progression.New diagnostic techniques that predict unfavorable outcomes are needed in order to improve treatment strategies.Circulating tumor cells(CTCs)are showing promising results as a predictive biomarker for various tumors.In this editorial we comment on the article by Zhang et al,who published the first systematic review and meta-analysis evaluating the prognostic value of CTCs as biomarkers in early-stage pancreatic cancer patients undergoing surgery.CTCs were detected in peripheral or central venous system blood,before or during surgery.Positive CTCs showed a correlation with decreased overall survival and decreased relapse-free,disease-free and progression-free survival in this meta-analysis.However,the heterogeneity was significant.The authors suggest that this result was related to the separation methods used between studies,but other differences such as the margin status or the neoadjuvant and adjuvant treatments used are also important to consider.CTCs may be a potential prognostic biomarker in pancreatic cancer patients,but it is necessary to compare and standardize the platforms used to isolate CTCs,to compare different biomarkers from liquid biopsy and to determine the impact on prognosis when therapeutic changes are made based on CTCs levels.

Desulfurization characteristics of slaked lime and regulation optimization of circulating fluidized bed flue gas desulfurization process--A combined experimental and numerical simulation study

Circulating fluidized bed flue gas desulfurization(CFB-FGD) process has been widely applied in recent years. However, high cost caused by the use of high-quality slaked lime and difficult operation due to the complex flow field are two issues which have received great attention. Accordingly, a laboratory-scale fluidized bed reactor was constructed to investigate the effects of physical properties and external conditions on desulfurization performance of slaked lime, and the conclusions were tried out in an industrial-scale CFB-FGD tower. After that, a numerical model of the tower was established based on computational particle fluid dynamics(CPFD) and two-film theory. After comparison and validation with actual operation data, the effects of operating parameters on gas-solid distribution and desulfurization characteristics were investigated. The results of experiments and industrial trials showed that the use of slaked lime with a calcium hydroxide content of approximately 80% and particle size greater than 40 μm could significantly reduce the cost of desulfurizer. Simulation results showed that the flow field in the desulfurization tower was skewed under the influence of circulating ash. We obtained optimal operating conditions of 7.5 kg·s^(-1)for the atomized water flow, 70 kg·s^(-1)for circulating ash flow, and 0.56 kg·s^(-1)for slaked lime flow, with desulfurization efficiency reaching 98.19% and the exit flue gas meeting the ultraclean emission and safety requirements. All parameters selected in the simulation were based on engineering examples and had certain application reference significance.

Recovery of alumina from circulating fluidized bed combustion Al-rich fly ash using mild hydrochemical process

To utilize CFBC Al-rich fly ash, a mild hydrochemical extraction process was investigated for recovery of alumina. An alumina extraction efficiency of 92.31%was attained using a 45%NaOH solution, an original caustic ratio （molar ratio of Na2O to Al2O3 in the sodium aluminate solution） of 25, a molar ratio of CaO to SiO2 in the fly ash of 1.1, a liquid volume to solid mass ratio of 9, a reaction temperature of 280 ℃, and a residence time of 1 h when treating fly ash with an alumina to silica mass ratio （A/S） of 0.78 and an alumina content of 32.43%. Additionally, the alumina leaching mechanism was explored via structural and chemical analysis, which revealed that after alkaline digestion, the main solid phase containing silica was NaCaHSiO4 with a theoretical A/S of zero.

SO_2 emission characteristics from co-firing of petroleum coke and coal in circulating fluidized bed

Combustion and sulfur retention experiments of mixed fuel of petroleum cokeand coal were conducted on a pilot-scale circulating fluidized bed (CFB) combustor with the thermalinput of 0. 6 MW. The effects of several parameters, such as the primary air percentage, excess aircoefficient, bed temperature, Ca/S molar ratio and mass ratio of petroleum coke to coal on SO_2emission were verified. Experimental results show that when the ratio of petroleum coke to coal inthe mixed fuel increases, the SO_2emission increases. The maximum SO_2 emission appears when purecoke burns. The SO_2 concentration in flue gas reduces with the increase in the primary airpercentage, excess air coefficient and Ca/S molar ratio for all kinds of fuel mixtures. Therangebetween 830 t and 850 t is the optimal temperature for sulfur retention during co-firing ofpetroleum coke and coal with the mass ratio R of 1 and 3 in CFB.

I MWth Test Facilities for Circulating Fluidized Bed Combustion

This paper presents the technical parameters and features of 1 MWth test facilities for circulating fluidized bed combustion (CFBC) at Thermal Power Research Institute (TPRI) of State Power Corporation (SP), introduces the test items that can be proceeded and trial combustion projects completed. The development status of CFBC technologies abroad and the level of China in this field are also introduced in the paper.

Experimental Studies on a Circulating Fluidized Bed for Flue Gas Desulfurization

The tests of flue gas desulfurization were carried out on a circulating fluidized bed reactor in which the flue gas had different velocities at different sections. The SO 2 removal efficiency could be as high as 80% when Ca/S molar ratio was 1 1 and a small amount of water was sprayed into the reactor by a two phase (gas liquid) system nozzle.

Circulating micro RNAs and long non-coding RNAs in gastric cancer diagnosis:An update and review

Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.

Circulating endothelial and progenitor cells:Evidence from acute and long-term exercise effects

Circulating bone-marrow-derived cells,named endothelial progenitor cells(EPCs),are capable of maintaining,generating,and replacing terminally differentiated cells within their own specific tissue as a consequence of physiological cell turnover or tissue damage due to injury.Endothelium maintenance and restoration of normal endothelial cell function is guaranteed by a complex physiological procedure in which EPCs play a significant role.Decreased number of peripheral blood EPCs has been associated with endothelial dysfunction and high cardiovascular risk.In this review,we initially report current knowledge with regard to the role of EPCs in healthy subjects and the clinical value of EPCs in different disease populations such as arterial hypertension,obstructive sleep-apnea syndrome,obesity,diabetes mellitus,peripheral arterial disease,coronary artery disease,pulmonary hypertension,and heart failure.Recent studies have introduced the novel concept that physical activity,either performed as a single exercise session or performed as part of an exercise training program,results in a significant increase of circulating EPCs.In the second part of this review we provide preliminary evidence from recent studies investigating the effects of acute and long-term exercise in healthy subjects and athletes as well as in disease populations.

Circulating micro RNAs as diagnostic and prognostic tools for hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is an aggressive malignancy and the second leading cause of cancerrelated deaths worldwide. Conventional biomarkers exhibit poor performance in the surveillance,diagnosis,and prognosis of HCC. Micro RNAs(mi RNAs) are a class of evolutionarily conserved small non-coding RNAs that are involved in the regulation of gene expression and protein translation,and they play critical roles in cell growth,differentiation,and the development of various types of cancers,including HCC. Recent evidence revealed the role of mi RNAs as potential novel and ideal biomarkers for HCC. mi RNAs are released to extracellular spaces,and they are extremely stable in bodily fluids,including serum or plasma,where they are packaged into various microparticles or associated with RNA-binding proteins. Numerous studies have demonstrated that circulating mi RNAs have potential applications as minimally invasive biomarkers for HCC diagnosis and prognosis. The present review highlights current understanding of mi RNA biogenesis and the origins and types of circulating mi RNAs. We summarize recent progress in the use of circulating mi RNAs as diagnostic and prognostic biomarkers for HCC. We also discuss the challenges and perspectives of the clinical utility of circulating mi RNAs in HCC.