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.

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.

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.

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.

慢性肾衰竭患者FGF23、α-Klotho与中医证型相关性研究

慢性肾脏病(CKD)起病隐匿,因其发病率高、知晓率低、诊断率低、预后差和医疗费用高等特点,已成为危害人类健康的重要公共卫生问题。CKD最终会进展成终末期肾脏病,其常见并发症之一就是慢性肾脏病-矿物质和骨代谢异常(CKD-MBD),进入透析阶段时CKD-MBD的发病率高达100%,严重影响透析患者的生存质量,且其是导致透析患者死亡的独立危险因素^([1])。故CKD-MBD的预防与治疗至关重要。CKD的病理基础是肾纤维化,符合中医学对癥积的认识。

Circulating tumor cells and circulating tumor DNA in breast cancer diagnosis and monitoring

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is becoming more popular as a diagnostic tool in the clinical management of breast cancer.Elevated concentrations of these biomarkers during cancer treatment may be used as markers for cancer progression as well as to understand the mechanisms underlying metastasis and treatment resistance.Thus,these circulating markers serve as tools for cancer assessing and monitoring through a simple,non-invasive blood draw.However,despite several study results currently noting a potential clinical impact of ctDNA mutation tracking,the method is not used clinically in cancer diagnosis among patients and more studies are required to confirm it.This review focuses on understanding circulating tumor biomarkers,especially in breast cancer.

Recent progress in aptamer-based microfluidics for the detection of circulating tumor cells and extracellular vesicles

Liquid biopsy is a technology that exhibits potential to detect cancer early,monitor therapies,and predict cancer prognosis due to its unique characteristics,including noninvasive sampling and real-time analysis.Circulating tumor cells(CTCs)and extracellular vesicles(EVs)are two important components of circulating targets,carrying substantial disease-related molecular information and playing a key role in liquid biopsy.Aptamers are single-stranded oligonucleotides with superior affinity and specificity,and they can bind to targets by folding into unique tertiary structures.Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools.In this review,we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches.Then,we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection.Finally,we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

Characterization of Mycobacterium Species Circulating among Tuberculosis Patients in Bayelsa State, Nigeria

Introduction: Tuberculosis is caused by infection with Mycobacterium tuberculosis. Looking at the evolution of the bacterium gene due to mutation is crucial to identify species circulating among patients in an area. WHO speculated that tuberculosis is caused by M. tuberculosis (MTB), but identification of the strains of MTB circulating in a particular area is important for the management of MTB and to identify pulmonary infections caused by non-tuberculosis mycobacterium. Contact tracing of drug resistant MTB in circulation in an area is also an important procedure of MTB therapeutic choice. Aim: This study aimed to isolate and identify Mycobacterium species circulating in Bayelsa State, Nigeria. Materials and Methods: A total of 102 sputum samples collected from MTB patients were cultured in Lowenstein Jensen (LJ) solid media. Isolates on LJ media were confirmed using Zeihl Nelseen staining method for AFB and Standard Diagnosis Bioline TB Ag MPT64 Rapid test kit. The 16s rRNA gene amplification, agarose gel electrophoresis, and gene sequencing were conducted. Phylogenic analysis and evolutional distances of the strains are computed using the Juke-cantor method. Result: Out of 102 sputum samples examined 15 (14.7%) had growth of Mycobacterium species (AFB positive). The extracted DNA of MTB amplified on agarose gel electrophoresis aligned horizontally at lanes 1 - 15 showing 16S gene band (1500 bp). Two 2 (2.0%) are non-tuberculosis Mycobacteria species, while 13 (12.7%) were M. tuberculosis. The non-tuberculosis Mycobacterium species isolated are Mycobacteriode abscesses and Mycobacterium kansassii strain FDAARGOS 1534. The tuberculosis strains are Mycobacterium tuberculosis MG003 and R2092 but the predominant strain was MG003. The degree of the genetic evolution of the non-MTB Mycobacterium kansassii strain FDAARGOS 1534 was 75.4%. Conclusion: The two major strains of Mycobacterium tuberculosis (MTB) circulating in Bayelsa State are MTB MG003 and MTB R2092;MTB MG003 was predominant. The non-tuberculosis species are Mycobacteriode abscesses and Mycobacterium kansasii.

血清FGF23-Klotho轴对多发性骨髓瘤患者合并肾损伤的预测价值

目的:探讨分析血清FGF23-Klotho轴对多发性骨髓瘤(MM)患者合并肾损伤的预测价值。方法:选择我院收治的104例MM患者作为MM组,并根据患者是否存在肾损伤,将其分为肾损伤组(n=34)和非肾损伤组(n=70)。同期选取在我院健康体检的受试者80例作为对照组。检测各组受试者肾功能相关性指标血清胱抑素C(Cys-C)、血肌酐(Scr)、β2微球蛋白(β2-MG)表达,以及血清FGF23以及Klotho表达,并计算FGF23/Klotho比值。采用二元Logistic回归分析血清FGF23、Klotho对MM患者并发肾损伤的影响;采用ROC曲线分析血清FGF23、Klotho对MM合并肾损伤的预测价值;并分析肾损伤组患者血清FGF23、Klotho与Cys-C、Scr、β2-MG相关性。结果:MM组患者血清Cys-C、Scr、β2-MG以及FGF23水平均显著高于对照组,而MM组患者血清Klotho水平显著低于对照组(P<0.05),MM组患者FGF23/Klotho比值显著高于对照组(P<0.05)。在MM患者中,肾损伤组患者血清Cys-C、Scr、β2-MG以及FGF23水平均显著高于非肾损伤组(P<0.05),而肾损伤组患者血清Klotho水平显著低于非肾损伤组(P<0.05)。采用二元Logistic回归分析血清FGF23、Klotho对MM并发肾损伤的影响,结果显示血清FGF23、Klotho均进入回归模型(P<0.05),为影响MM并发肾损伤的重要因素。采用ROC曲线分析血清FGF23、Klotho以及FGF23/Klotho比值对MM合并肾损伤的预测价值,曲线下面积分别为0.839、0.831以及0.962。相关性分析结果显示,肾损伤组患者血清FGF23、FGF23/Klotho比值与Cys-C、Scr、β2-MG呈显著正相关关系(P<0.05),血清Klotho与Cys-C、Scr、β2-MG呈显著负相关关系(P<0.05)。结论:血清FGF23-Klotho轴在多发性骨髓瘤并发肾损伤中具有重要调控价值,与患者肾功能密切相关,对多发性骨髓瘤患者肾损伤的发生具有着重要的预测价值,值得临床进一步深入研究。

老年白内障患者血清HO-1、α-Klotho水平与氧化应激指标的关系及其诊断价值

目的探讨老年白内障患者血清血红素氧合酶1(HO-1)、α-Klotho水平与氧化应激指标的关系及其诊断价值。方法选取2021年6月至2023年6月于如皋市人民医院就诊的老年白内障患者121例作为白内障组,并选取同期该院年龄、性别相匹配的体检健康者123例作为对照组。收集两组临床资料并采用酶联免疫吸附试验法检测两组血清HO-1、α-Klotho水平及血清氧化应激相关指标[超氧化物歧化酶(SOD)、脂质过氧化物(LPO)、丙二醛(MDA)、总抗氧化能力(TAC)、谷胱甘肽过氧化物酶(GSH-Px)]。Pearson相关性分析血清HO-1、α-Klotho水平与氧化应激指标的相关性。采用受试者工作特征(ROC)曲线分析血清HO-1、α-Klotho水平对老年白内障的诊断价值,多因素Logistic回归分析影响老年白内障发生的因素。结果白内障组血清HO-1、α-Klotho水平均低于对照组,差异均有统计学意义(P<0.05)。白内障组血清SOD、GSH-Px水平低于对照组,LPO、MDA、TAC水平高于对照组,差异均有统计学意义(P<0.05)。血清HO-1、α-Klotho与SOD、GSH-Px呈正相关(P<0.05),与LPO、MDA、TAC呈负相关(P<0.05)。ROC曲线分析结果显示,HO-1、α-Klotho二者联合诊断老年白内障的曲线下面积为0.912(95%CI:0.869~0.944),其灵敏度为78.51%,特异度为90.24%,二者联合诊断优于HO-1、α-Klotho单独诊断(Z=4.358、4.075,P<0.001)。多因素Logistic回归分析结果显示,HO-1、α-Klotho是影响老年白内障发生的保护因素,糖尿病是影响老年白内障发生的危险因素(P<0.05)。结论老年白内障患者血清HO-1、α-Klotho水平降低,与氧化应激指标密切相关,且HO-1、α-Klotho对老年白内障有一定的诊断价值。

Circulating tumor cells: Biological features and survival mechanisms

Circulating tumor cells(CTCs)are neoplastic cells that are detached from primary tumors and enter circulation.Enumeration and characterization of CTCs are of significance in cancer diagnosis,prognosis,and treatment monitoring.CTC survival in the bloodstream is a limiting step for the development of metastases in distant organs.Recent technological advances,especially in single-cell molecular analyses have uncovered heterogeneous CTC survival mechanisms.Undergoing epithelial-to-mesenchymal transition(EMT),increasing stem cell-like properties,and forming cell clusters enable CTCs to adapt to the harsh microenvironment of the circulation.Expressing and releasing several immunosuppressive molecules help CTCs escape from anti-cancer immune mechanisms.This review article summarizes the biological characteristics of CTCs and focuses on the recent understanding of the mechanisms by which CTCs survive in circulation.Additionally,the clinical and therapeutic implications of CTCs are discussed.