Regional dynamic cerebral autoregulation across anterior and posterior circulatory territories:A detailed exploration and its clinical implications

Cerebral autoregulation(CA)is the mechanism that maintains stable cerebral blood flow(CBF)despite fluctuations in systemic blood pressure,crucial for brain homeostasis.Recent evidence highlights distinct regional variations in CA between the anterior(carotid)and posterior(vertebrobasilar)circulations.Noninvasive neuromonitoring techniques,such as transcranial Doppler,transfer function analysis,and near-infrared spectroscopy,facilitate the dynamic assessment of CBF and autoregulation.Studies indicate a robust autoregulatory capacity in the anterior circulation,characterized by rapid adjustments in vascular resistance.On the contrary,the posterior circulation,mainly supplied by the vertebral arteries,may have a lower autoregulatory capacity.in acute brain injuries such as intracerebral and subarachnoid hemorrhage,and traumatic brain injuries,dynamic CA can be significantly altered in the posterior circulation.Proposed physiological mechanisms of impaired CA in the posterior circulation include:(1)Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity;(2)Endothelial dysfunction;(3)Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBFmetabolism(i.e.,neurovascular)uncoupling;and(4)Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances(e.g.nitric oxide,potassium,and calcium ions).Furthermore,more research is needed on the effects of collateral circulation,as well as the circle of Willis variants,such as the fetal-type posterior cerebral artery,on dynamic CA.Improving our understanding of these mechanisms is crucial to improving the diagnosis,prognosis,and management of various cerebrovascular disorders.

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.

Heterojunction-engineered carrier transport in elevated-metal metal-oxide thin-film transistors

This study investigates the carrier transport of heterojunction channel in oxide semiconductor thin-film transistor(TFT)using the elevated-metal metal-oxide(EMMO)architecture and indium−zinc oxide(InZnO).The heterojunction band diagram of InZnO bilayer was modified by the cation composition to form the two-dimensional electron gas(2DEG)at the interface quantum well,as verified using a metal−insulator−semiconductor(MIS)device.Although the 2DEG indeed contributes to a higher mobility than the monolayer channel,the competition and cooperation between the gate field and the built-in field strongly affect such mobility-boosting effect,originating from the carrier inelastic collision at the heterojunction interface and the gate field-induced suppression of quantum well.Benefited from the proper energy-band engineering,a high mobility of 84.3 cm2·V^(−1)·s^(−1),a decent threshold voltage(V_(th))of−6.5 V,and a steep subthreshold swing(SS)of 0.29 V/dec were obtained in InZnO-based heterojunction TFT.

Indispensable gutter layers in thin-film composite membranes for carbon capture

Industrial thin-film composite(TFC)membranes achieve superior gas separation properties from high-performance selective layer materials,while the success of membrane technology relies on high-performance gutter layers to achieve production scalability and low-cost manufacturing.However,the current literature predominantly focuses on the design of polymer architectures to obtain high permeability and selectivity,while the art of fabricating gutter layers is usually safeguarded by industrial manufacturers and appears lackluster to academic researchers.This is the first report aiming to provide a comprehensive and critical review of state-of-the-art gutter layer materials and their design and modification to enable TFC membranes with superior separation performance.We first elucidate the importance of the gutter layer on membrane performance through modeling and experimental results.Then various gutter layer materials used to obtain high-performance composite membranes are critically reviewed,and the strategies to improve their compatibility with the selective layer are highlighted,such as oxygen plasma treatment,polydopamine deposition,and surface grafting.Finally,we present the opportunities of the gutter layer design for practical applications.

Low-Volatile Binder Enables Thermal Shock-Resistant Thin-Film Cathodes for Thermal Batteries

Manufacturing thin-film components is crucial for achieving high-efficiency and high-power thermal batteries(TBs).However,developing binders with low-gas production at the operating temperature range of TBs(400-550°C)has proven to be a significant challenge.Here,we report the use of acrylic acid derivative terpolymer(LA136D)as a low-volatile binder for thin-film cathode fabrication and studied the chain scission and chemical bondbreaking mechanisms in pyrolysis.It is shown LA136D defers to randomchain scission and cross-linking chain scission mechanisms,which gifts it with a low proportion of volatile products(ψ,ψ=39.2 wt%)at even up to 550°C,well below those of the conventional PVDF(77.6 wt%)and SBR(99.2 wt%)binders.Surprisingly,LA136D contributes to constructing a thermal shock-resistant cathode due to the step-by-step bond-breaking process.This is beneficial for the overall performance of TBs.In discharging test,the thin-film cathodes exhibited a remarkable 440%reduction in polarization and 300%enhancement in the utilization efficiency of cathode materials,while with just a slight increase of 0.05 MPa in gas pressure compared with traditional“thick-film”cathode.Our work highlights the potential of LA136D as a low-volatile binder for thin-film cathodes and shows the feasibility of manufacturing high-efficiency and high-power TBs through polymer molecule engineering.

Implementation of sub-100 nm vertical channel-all-around(CAA) thin-film transistor using thermal atomic layer deposited IGZO channel

In-Ga-Zn-O(IGZO) channel based thin-film transistors(TFT), which exhibit high on-off current ratio and relatively high mobility, has been widely researched due to its back end of line(BEOL)-compatible potential for the next generation dynamic random access memory(DRAM) application. In this work, thermal atomic layer deposition(TALD) indium gallium zinc oxide(IGZO) technology was explored. It was found that the atomic composition and the physical properties of the IGZO films can be modulated by changing the sub-cycles number during atomic layer deposition(ALD) process. In addition, thin-film transistors(TFTs) with vertical channel-all-around(CAA) structure were realized to explore the influence of different IGZO films as channel layers on the performance of transistors. Our research demonstrates that TALD is crucial for high density integration technology, and the proposed vertical IGZO CAA-TFT provides a feasible path to break through the technical problems for the continuous scale of electronic equipment.

Uncertainties of ENSO-related Regional Hadley Circulation Anomalies within Eight Reanalysis Datasets

El Nino-Southern Oscillation(ENSO),the leading mode of global interannual variability,usually intensifies the Hadley Circulation(HC),and meanwhile constrains its meridional extension,leading to an equatorward movement of the jet system.Previous studies have investigated the response of HC to ENSO events using different reanalysis datasets and evaluated their capability in capturing the main features of ENSO-associated HC anomalies.However,these studies mainly focused on the global HC,represented by a zonal-mean mass stream function(MSF).Comparatively fewer studies have evaluated HC responses from a regional perspective,partly due to the prerequisite of the Stokes MSF,which prevents us from integrating a regional HC.In this study,we adopt a recently developed technique to construct the three-dimensional structure of HC and evaluate the capability of eight state-of-the-art reanalyses in reproducing the regional HC response to ENSO events.Results show that all eight reanalyses reproduce the spatial structure of HC responses well,with an intensified HC around the central-eastern Pacific but weakened circulations around the Indo-Pacific warm pool and tropical Atlantic.The spatial correlation coefficient of the three-dimensional HC anomalies among the different datasets is always larger than 0.93.However,these datasets may not capture the amplitudes of the HC responses well.This uncertainty is especially large for ENSO-associated equatorially asymmetric HC anomalies,with the maximum amplitude in Climate Forecast System Reanalysis(CFSR)being about 2.7 times the minimum value in the Twentieth Century Reanalysis(20CR).One should be careful when using reanalysis data to evaluate the intensity of ENSO-associated HC anomalies.

Generation of broadband polarization-orthogonal photon pairs via the dispersion-engineered thin-film lithium niobate waveguide

Broadband photon pairs are highly desirable for quantum metrology,quantum sensing,and quantum communication.Such sources are usually designed through type-0 phase-matching spontaneous parametric down-conversion(SPDC)that makes the photon pairs hard to separate in the frequency-degenerate case and thus limits their applications.In this paper,we design a broadband frequency-degenerate telecom-band photon pair source via the type-II SPDC in a dispersion-engineered thin-film lithium niobate waveguide,where the polarization modes of photon pairs are orthogonal and thus are easily separated deterministically.With a 5-mm-long waveguide,our design can achieve a bandwidth of 5.56 THz(44.8 nm),which is 8.6 times larger than that of the bulk lithium niobate,and the central wavelength can be flexibly adjusted.Our design is a promising approach towards high-quality integrated photon sources and may have wide applications in photonic quantum technologies.

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.

Fracture sealing performance of granular lost circulation materials at elevated temperature:A theoretical and coupled CFD-DEM simulation study

Lost circulation is a common downhole problem of drilling in geothermal and high-temperature,high-pressure(HTHP)formations.Lost circulation material(LCM)is a regular preventive and remedial measure for lost circulation.However,conventional LCMs seem ineffective in high-temperature formations.This may be due to the changes in the mechanical properties of LCMs and their sealing performance under high-temperature conditions.To understand how high temperature affects the fracture sealing performance of LCMs,we developed a coupled computational fluid dynamics-discrete element method(CFD-DEM)model to simulate the behavior of granular LCMs in fractures.We summarized the literature on the effects of high temperature on the mechanical properties of LCMs and the rheological properties of drilling fluid.We conducted sensitivity analyses to investigate how changing LCM slurry properties affected the fracture sealing efficiency at increasing temperatures.The results show that high temperature reduces the size,strength,and friction coefficient of LCMs as well as the drilling fluid viscosity.Smaller,softer,and less frictional LCM particles have lower bridging probability and slower bridging initiation.Smaller particles tend to form dual-particle bridges rather than single-particle bridges.These result in a deeper,tighter,but unstable sealing zone.Reduced drilling fluid viscosity leads to faster and shallower sealing zones.

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.

Arterial Duct Stenting Versus Modified Blalock-Taussig Shunt in Patient with Ductal-Dependent Pulmonary Circulation: Systematic Review & Meta-Analysis

Objective:Patients with ductal-dependent pulmonary circulation require alternative bloodflow to provide and maintain adequate oxygenation.Modified Blalock-Taussig Shunt(MBTS)has been the standard for providing such a result.Currently,less invasive methods such as Arterial Duct(AD)stenting have been performed as alter-natives.This study aims to compare the outcome of AD stenting and MBTS.Method:Systematic research was performed in online databases using the PRISMA protocol.The outcomes measured were 30-day mortality,com-plication,unplanned intervention,oxygen saturation,duration of hospital,and ICU length of stay.Any compara-tive study provided with full text is included.The outcome of each study was analyzed using a trandom effects model with relative risk and mean difference as the effect size.Bias risk assessment was conducted using the New-castle-Ottawa Scale.All analyses were performed using Review Manager 5.4.1.Result:A total of 11 studies with 3154 samples included in this study.There is no significant difference in 30-day mortality between the two groups(p-value=0.10).However,there is significantly less complication(RR 0.53[0.35,0.82];p-value=0.004)and unplanned intervention(RR 0.59[0.38,0.92];p-value=0.02)in the AD stent group.Comparison of the Nakata index showed no significant difference(p-value=0.88).Post-operative oxygen saturation was measured signifi-cantly higher in the AD stenting(MD 1.80[0.85,2.74];p-value=0.0002).However,AD stent group shows sig-nificantly lower long-term oxygen saturation(MD-8.43[-14.38,-2.48];p-value=0.005).Both hospital and ICU length of stay was significantly shorter in the AD stent group(MD-8.30[-11.13,-5.48];p-value<0.00001;MD-5.09[-7.79,-2.38];p-value=0.0002).Conclusion:AD stenting provides comparable outcomes relative to MBTS as it provides less complication and unplanned intervention and higher post-procedural O2 saturation.However,MBTS proved its superiority in maintaining higher long-term oxygen saturation and still became the preferred option to manage complex cases where stenting is either challenging or unsuccessful.

A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study

BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest patients.This study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ROSC.METHODS:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to 2014.Patients’general information,ETCO_(2),and POP parameters were collected and statistically analyzed.RESULTS:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC episodes.The 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),respectively.CONCLUSION:Patients with unsustained ROSC have a poor prognosis.The combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.

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.