Nomogram based on liver stiffness and spleen area with ultrasound for posthepatectomy liver failure:A multicenter study

BACKGROUND Liver stiffness(LS)measurement with two-dimensional shear wave elastography(2D-SWE)correlates with the degree of liver fibrosis and thus indirectly reflects liver function reserve.The size of the spleen increases due to tissue proliferation,fibrosis,and portal vein congestion,which can indirectly reflect the situation of liver fibrosis/cirrhosis.It was reported that the size of the spleen was related to posthepatectomy liver failure(PHLF).So far,there has been no study combining 2D-SWE measurements of LS with spleen size to predict PHLF.This prospective study aimed to investigate the utility of 2D-SWE assessing LS and spleen area(SPA)for the prediction of PHLF in hepatocellular carcinoma(HCC)patients and to develop a risk prediction model.AIM To investigate the utility of 2D-SWE assessing LS and SPA for the prediction of PHLF in HCC patients and to develop a risk prediction model.METHODS This was a multicenter observational study prospectively analyzing patients who underwent hepatectomy from October 2020 to March 2022.Within 1 wk before partial hepatectomy,ultrasound examination was performed to measure LS and SPA,and blood was drawn to evaluate the patient’s liver function and other conditions.Least absolute shrinkage and selection operator logistic regression and multivariate logistic regression analysis was applied to identify independent predictors of PHLF and develop a nomogram.Nomogram performance was validated further.The diagnostic performance of the nomogram was evaluated with receiver operating charac-teristic curve compared with the conventional models,including the model for end-stage liver disease(MELD)score and the albumin-bilirubin(ALBI)score.RESULTS A total of 562 HCC patients undergoing hepatectomy(500 in the training cohort and 62 in the validation cohort)were enrolled in this study.The independent predictors of PHLF were LS,SPA,range of resection,blood loss,international normalized ratio,and total bilirubin.Better diagnostic performance of the nomogram was obtained in the training[area under receiver operating characteristic curve(AUC):0.833;95%confidence interval(95%CI):0.792-0.873;sensitivity:83.1%;specificity:73.5%]and validation(AUC:0.802;95%CI:0.684-0.920;sensitivity:95.5%;specificity:52.5%)cohorts compared with the MELD score and the ALBI score.CONCLUSION This PHLF nomogram,mainly based on LS by 2D-SWE and SPA,was useful in predicting PHLF in HCC patients and presented better than MELD score and ALBI score.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Power Relations in Older Adults’ Cognitive Interaction in Clinical Setting: A Multimodal Pragmatic Perspective

This study explored the construction of power relations in the cognitive assessment of older adults within the Chinese clinical context.Data is derived from audio and video recordings that nine older adults produced in the cognitive assessment of the Chinese version of the Montreal Cognitive Assessment-Basic(MoCA-B),which were then annotated and analyzed from a multimodal pragmatic perspective.The study reveals that examiners and older adults employed various speech acts to achieve distinct communicative goals,with power relations between them being reflected through these speech acts.Examiners tend to claim high power,utilizing discourse strategies such as request,interruption,evaluation,rhetorical questions,and directive speech acts.In contrast,older adults assert high power through directive speech acts,rhetorical questions,and interruptions.Both parties also exhibit low power by using confirming questions and explanations.Additionally,gestures,smiles,prosody features,and other non-verbal communicative resources are synergistically employed to exercise power.The interactive mechanism of constructing power relations reveals that age affects older adults’power relations construction even in a professional setting of the Chinese context.The negotiation between the advanced age of older adults and the expertise of examiners jointly shapes power relations in their interactions.

Inhibition of fibroblast activation protein ameliorates cartilage matrix degradation and osteoarthritis progression

Fibroblast activation protein(Fap)is a serine protease that degrades denatured type I collagen,α2-antiplasmin and FGF21.Fap is highly expressed in bone marrow stromal cells and functions as an osteogenic suppressor and can be inhibited by the bone growth factor Osteolectin(Oln).Fap is also expressed in synovial fibroblasts and positively correlated with the severity of rheumatoid arthritis(RA).However,whether Fap plays a critical role in osteoarthritis(OA)remains poorly understood.Here,we found that Fap is significantly elevated in osteoarthritic synovium,while the genetic deletion or pharmacological inhibition of Fap significantly ameliorated posttraumatic OA in mice.Mechanistically,we found that Fap degrades denatured type II collagen(Col II)and Mmp13-cleaved native Col II.Intra-articular injection of r Fap significantly accelerated Col II degradation and OA progression.In contrast,Oln is expressed in the superficial layer of articular cartilage and is significantly downregulated in OA.Genetic deletion of Oln significantly exacerbated OA progression,which was partially rescued by Fap deletion or inhibition.Intra-articular injection of r Oln significantly ameliorated OA progression.Taken together,these findings identify Fap as a critical pathogenic factor in OA that could be targeted by both synthetic and endogenous inhibitors to ameliorate articular cartilage degradation.

Icaritin inhibits the progression of urothelial cancer by suppressing PADI2-mediated neutrophil infiltration and neutrophil extracellular trap formation

Tumor relapse and metastasis are the major causes of mortality associated with urothelial cancer.In the tumor microenvironment,negative regulatory molecules and various immune cell subtypes suppress antitumor immunity.The inflammatory microenvironment,associated with neutrophils and neutrophil extracellular traps(NETs),promotes tumor metastasis.However,no drugs are currently available to specifically inhibit neutrophils and NETs.In this study,we first demonstrated that icaritin(ICT),a Chinese herbal remedy that is a first-line treatment for advanced and incurable hepatocellular carcinoma,reduces NETs caused by suicidal NETosis and prevents neutrophil infiltration in the tumor microenvironment.Mechanistically,ICT binds to and inhibits the expression of PADI2 in neutrophils,thereby suppressing PADI2-mediated histone citrullination.Moreover,ICT inhibits ROS generation,suppresses the MAPK signaling pathway,and inhibits NET-induced tumor metastasis.Simultaneously,ICT inhibits tumoral PADI2-mediated histone citrullination,which consequently suppresses the transcription of neutrophil-recruiting genes such as GM-CSF and IL-6.The downregulation of IL-6 expression,in turn,forms a regulatory feedback loop through the JAK2/STAT3/IL-6 axis.Through a retrospective study of clinical samples,we found a correlation between neutrophils,NETs,UCa prognosis,and immune evasion.Combining ICT with immune checkpoint inhibitors may have synergistic effects.In summary,our study demonstrated that ICT could be a novel inhibitor of NETs and a novel UCa treatment.

Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome

The incidence of frailty gradually increases with age.This condition places a heavy burden on modern society,of which the aging population is increasing.Frailty is one of the most complicated clinical syndromes;thus,it is difficult to uncover its underlying mechanisms.Oxidative stress(OS)is involved in frailty in multiple ways.The association between the gut microbiota(GM)and frailty was recently reported.Herein,we propose that OS is involved in the association between the GM and the occurrence of frailty syndrome.An imbalance between oxidation and antioxidants can eventually lead to frailty,and the GM probably participates in this process through the production of reactive oxygen species.On the other hand,OS can disturb the GM.Such dysbiosis consequently induces or exacerbates tissue damage,leading to the occurrence of frailty syndrome.Finally,we discuss the possibility of improving frailty by intervening in the vicious cycle between the imbalance of OS and dysbiosis.

Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints

Background Gaining more information about the reciprocal associations between different biomarkers within the ATN(Amyloid/Tau/Neurodegeneration)framework across the Alzheimer’s disease(AD)spectrum is clinically relevant.We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography(PET)ATN biomarkers in subjects with cognitive complaints.Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging(18F-florbetapir for A,18F-Florzolotau for T,and 18F-fluorodeoxyglucose[18F-FDG]for N)was enrolled(n=137).Theβ-amyloid(Aβ)status(positive versus negative)and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances.Results Plasma phosphorylated tau 181(p-tau181)level was found to be associated with PET imaging of ATN biomarkers in the entire cohort.Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+and Aβ−subjects.An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+subjects.Additionally,glucose hypometabolism-along with elevated plasma neurofilament light chain level-was related to more severe cognitive impairment in Aβ−subjects.Conclusion Plasma p-tau181,as well as 18F-florbetapir and 18F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβstatus in symptomatic stages of AD.18F-Florzolotau and 18F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment.Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.

Adjustment for the Age-and Gender-Related Metabolic Changes Improves the Differential Diagnosis of Parkinsonism

Age and gender are the important factors for brain metabolic declines in both normal aging and neurodegeneration,and the confounding effects may influence early and differential diagnosis of neurodegenerative diseases based on the[^(18)F]fluorodeoxyglucose positron emission tomography([^(18)F]FDG PET).We aimed to explore the potential of the adjustment of age-and gender-related confounding factors on[^(18)F]FDG PET images in differentiation of Parkinson’s disease(PD),multiple system atrophy(MSA)and progressive supra-nuclear palsy(PSP).Eight hundred and seventy-seven clinically definitely diagnosed Parkinsonian patients from a benchmark Huashan Parkinsonian PET imaging database were included.An age-and gender-adjusted Z(AGAZ)score was established based on the gender-specific longitudinal metabolic changes on healthy subjects.AGAZ scores and standardized uptake value ratio(SUVR)values were quantified at regional-level and support vector machine-based error-correcting output codes method was applied for classification.Additional references of the classifications based on metabolic pattern scores were included.The feature-based AGAZ score showed the best performance in classification(accuracy for PD,MSA,PSP:93.1%,96.3%,94.8%).In both genders,the AGAZ score con-sistently achieved the best efficiency,and the improvements compared to the conventional SUVR value for PD,MSA,and PSP mainly laid in specificity(Male:5.7%;Female:11.1%),sensitivity(Male:7.2%;Female:7.3%),and sensitivity(Male:7.3%;Female:17.2%).Female patients benefited more from the adjustment on[^(18)F]FDG PET in MSA and PSP groups(absolute net reclassification index,p<0.001).Collectively,the adjustment of age-and gender-related confounding factors may improve the differential diagnosis of Parkinsonism.Particularly,the diagnosis of female Parkinsonian population has the best improvement from this correction.

The chemerin-CMKLR1 axis in keratinocytes impairs innate host defense against cutaneous Staphylococcus aureus infection

The skin is the most common site of Staphylococcus aureus infection,which can lead to various diseases,including invasive and life-threatening infections,through evasion of host defense.However,little is known about the host factors that facilitate the innate immune evasion of S.aureus in the skin.Chemerin,which is abundantly expressed in the skin and can be activated by proteases derived from S.aureus,has both direct bacteria-killing activity and immunomodulatory effects via interactions with its receptor CMKLR1.Here,we demonstrate that a lack of the chemerin/CMKLR1 axis increases the neutrophil-mediated host defense against S.aureus in a mouse model of cutaneous infection,whereas chemerin overexpression,which mimics high levels of chemerin in obese individuals,exacerbates S.aureus cutaneous infection.Mechanistically,we identified keratinocytes that express CMKLR1 as the main target of chemerin to suppress S.aureus-induced IL-33 expression,leading to impaired skin neutrophilia and bacterial clearance.CMKLR1 signaling specifically inhibits IL-33 expression induced by cell wall components but not secreted proteins of S.aureus by inhibiting Akt activation in mouse keratinocytes.Thus,our study revealed that the immunomodulatory effect of the chemerin/CMKLR1 axis mediates innate immune evasion of S.aureus in vivo and likely increases susceptibility to S.aureus infection in obese individuals.

Macrophage based drug delivery:Key challenges and strategies

As a natural immune cell and antigen presenting cell,macrophages have been studied and engineered to treat human diseases.Macrophages are well-suited for use as drug carriers because of their biological characteristics,such as excellent biocompatibility,long circulation,intrinsic inflammatory homing and phagocytosis.Meanwhile,macrophages’uniquely high plasticity and easy re-education polarization facilitates their use as part of efficacious therapeutics for the treatment of inflammatory diseases or tumors.Although recent studies have demonstrated promising advances in macrophage-based drug delivery,several challenges currently hinder further improvement of therapeutic effect and clinical application.This article focuses on the main challenges of utilizing macrophage-based drug delivery,from the selection of macrophage sources,drug loading,and maintenance of macrophage phenotypes,to drug migration and release at target sites.In addition,corresponding strategies and insights related to these challenges are described.Finally,we also provide perspective on shortcomings on the road to clinical translation and production.

The landscape and clinical relevance of intronic polyadenylation in human cancers

Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and dementia.Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia.Circulating metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.In a prospective community-based cohort in China(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood glucose.Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL components.These fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

SH2B1 Tunes Hippocampal ERK Signaling to Influence Fluid Intelligence in Humans and Mice

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

Fabrication of physical and chemical crosslinked hydrogels for bone tissue engineering

Bone tissue engineering has emerged as a significant research area that provides promising novel tools for the preparation of biomimetic hydrogels applied in bone-related diseases(e.g.,bone defects,cartilage damage,osteoarthritis,etc.).Herein,thermal sensitive polymers(e.g.,PNIPAAm,Soluplus,etc.)were introduced into main chains to fabricate biomimetic hydrogels with injectability and compatibility for those bone defect need minimally invasive surgery.Mineral ions(e.g.,calcium,copper,zinc,and magnesium),as an indispensable role in maintaining the balance of the organism,were linked with polymer chains to form functional hydrogels for accelerating bone regeneration.In the chemically triggered hydrogel section,advanced hydrogels crosslinked by different molecular agents(e.g.,genipin,dopamine,caffeic acid,and tannic acid)possess many advantages,including extensive selectivity,rapid gel-forming capacity and tunable mechanical property.Additionally,photo crosslinking hydrogel with rapid response and mild condition can be triggered by different photoinitiators(e.g.,I2959,LAP,eosin Y,riboflavin,etc.)under specific wavelength of light.Moreover,enzyme triggered hydrogels were also utilized in the tissue regeneration due to its rapid gel-forming capacity and excellent biocompatibility.Particularly,some key factors that can determine the therapy effect for bone tissue engineering were also mentioned.Finally,brief summaries and remaining issues on how to properly design clinical-oriented hydrogels were provided in this review.

STN-ANT plasticity is crucial for the motor control in Parkinson’s disease model

Dear Editor,Motor control as a function of the basal ganglia circuit is crucial for every aspect of life and movement disorders,such as Parkinson’s disease(PD).In PD,the progressive denervation of dopamine in the dorsal striatum leads to inhibition of the direct pathway and facilitation of the indirect pathway and results in activation of the subthalamic nucleus(STN)and globus pallidus internus(GPi),two important nuclei in the motor loop of basal ganglia.

Deep Clinical Phenotyping of Parkinson’s Disease: Towards a New Era of Research and Clinical Care

Despite recent advances in technology,clinical phenotyping of Parkinson’s disease(PD)has remained relatively limited as current assessments are mainly based on empirical observation and subjective categorical judgment at the clinic.A lack of comprehensive,objective,and quantifiable clinical phenotyping data has hindered our capacity to diagnose,assess patients’conditions,discover pathogenesis,identify preclinical stages and clinical subtypes,and evaluate new therapies.Therefore,deep clinical phenotyping of PD patients is a necessary step towards understanding PD pathology and improving clinical care.In this review,we present a growing community consensus and perspective on how to clinically phenotype this disease,that is,to phenotype the entire course of disease progression by integrating capacity,performance,and perception approaches with state-of-the-art technology.We also explore the most studied aspects of PD deep clinical phenotypes,namely,bradykinesia,tremor,dyskinesia and motor fluctuation,gait impairment,speech impairment,and non-motor phenotypes.

Using posterior part of the deltoid muscle as receptor and quality control with intra-operative electrophysiological examination in targeted muscle reinnervation for high-level upper extremity amputees

To the Editor:Targeted muscle reinnervation(TMR)is a surgical technique of multiple nerve transfers,providing a potential of improved intuitive prosthetic control via surface electromyography(sEMG)in the high-level upper extremity amputees.[1]However,there is a risk that some of the reinnervations might be unsuccessful,especially for the ulnar nerve.[2]Both the quality control of nerve stumps and the receptor are important factors for the surgery.Assessing the nerve stumps during the surgery and finding more muscles as receptor might address the problem.Biceps,triceps,and brachialis muscles were mostly chosen as receptors for reinnervation in the trans-humeral amputees.Pectoralis major and pectoralis minor were mostly chosen as receptors for reinnervation in the shoulder disarticulation patients.

Recommendations for the diagnosis and treatment of paroxysmal kinesigemc dyskinesia: an expert consensus in China

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes.Paroxysmal kinesigenic dyskinesia(PKD)is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology.Clinically,PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action.The major cause of primary PKD is genetic abnormalities,and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance.The proline-rich transmembrane protein 2(PRRT2)was the first identified causative gene of PKD,accounting for the majority of PKD cases worldwide.An increasing number of studies has revealed the clinical and genetic characteristics,as well as the underlying mechanisms of PKD.By seeking the views of domestic experts,we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD.In this consensus,we review the clinical manifestations,etiology,clinical diagnostic criteria and therapeutic recommendations for PKD,and results of genetic analyses in PKD patients performed in domestic hospitals.

Xuebijing alleviates LPS-induced acute lung injury by downregulating pro-inflammatory cytokine production and inhibiting gasdermin-E-mediated pyroptosis of alveolar epithelial cells

Acute lung injury/acute respiratory distress syndrome(ALI/ARDS)is characterized by diffuse alveolar injury primarily caused by an excessive inflammatory response.Regrettably,the lack of effective pharmacotherapy currently available contributes to the high mortality rate in patients with this condition.Xuebijing(XBJ),a traditional Chinese medicine recognized for its potent anti-inflammatory properties,exhibits promise as a potential therapeutic agent for ALI/ARDS.This study aimed to explore the preventive effects of XBJ on ALI and its underlying mechanism.To this end,we established an LPS-induced ALI model and treated ALI mice with XBJ.Our results demonstrated that pre-treatment with XBJ significantly alleviated lung inflammation and increased the survival rate of ALI mice by 37.5%.Moreover,XBJ substantially suppressed the production of TNF-α,IL-6,and IL-1βin the lung tissue.Subsequently,we performed a network pharmacology analysis and identified identified 109 potential target genes of XBJ that were mainly involved in multiple signaling pathways related to programmed cell death and anti-inflammatory responses.Furthermore,we found that XBJ exerted its inhibitory effect on gasdermin-E-mediated pyroptosis of lung cells by suppressing TNF-αproduction.Therefore,this study not only establishes the preventive efficacy of XBJ in ALI but also reveals its role in protecting alveolar epithelial cells against gasdermin-E-mediated pyroptosis by reducing TNF-αrelease.

阿尔茨海默病的血液生物标志物:一项基于中国多中心的横断面和纵向研究

阿尔茨海默病(AD)的生物标志物在血液中含量可能因种族、老年性疾病与各种环境风险因素等不同而存在差异,尚缺乏系统性的研究来评估AD生物标志物在中国老年及AD患者人群中的变化以及是否具有准确预测脑内淀粉样蛋白沉积的能力.本工作为一项多中心纵向队列研究,共纳入来自全国各地6个不同临床中心的817个血液样本.研究测量了多个国际上通用的AD生物标志物,包括β-淀粉样蛋白40与42、磷酸化Tau(pTau)蛋白、总Tau蛋白、神经纤维丝轻链(NFL)和胶质纤维酸性蛋白(GFAP),并使用淀粉样斑块PET示踪剂和核磁结构影像对受试者进行综合评估.研究发现,APOE基因型与血浆pTau或血清GFAP组合的预测模型对脑内淀粉样斑块的沉积状态具有较好的区分能力.此外,研究还发现GFAP基线水平越高的患者其神经退行性变的速度越快.本研究结果基于多中心数据,论证了AD血液生物标志物在中国汉族人群中的实用性和应用前景,提示了血液pTau和GFAP是检测AD早期症状的有效指标,为我国AD的早期诊断和治疗提供了参考.