Biomarkers in Neuropsychiatry最新文献_第7页

A meta-analysis of the relationship between sleep and β-Amyloid biomarkers in Alzheimer’s disease 阿尔茨海默病患者睡眠与β-淀粉样生物标志物关系的荟萃分析

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-06-16 DOI: 10.1016/j.bionps.2023.100068

Jana Harenbrock , Heinz Holling , Graham Reid , Ivan Koychev

{"title":"A meta-analysis of the relationship between sleep and β-Amyloid biomarkers in Alzheimer’s disease","authors":"Jana Harenbrock , Heinz Holling , Graham Reid , Ivan Koychev","doi":"10.1016/j.bionps.2023.100068","DOIUrl":"https://doi.org/10.1016/j.bionps.2023.100068","url":null,"abstract":"<div><p>Sleep has an important role for long-term memory consolidation. As deficits in learning and memory are clinical characteristics of Alzheimer’s disease (AD), it has been suggested that disruptions in sleep-mediated consolidation processes are related to AD. Indeed, sleep disruptions and sleep disorders are often comorbid with AD and perhaps precede the onset of AD symptoms as a risk factor. Additionally, research has shown that sleep disruptions and disorders are associated with accumulation of β-amyloid (AB), a neuropathologic hallmark and biomarker of AD. However, the studies that have investigated the relationship between sleep disturbances and AB burden have been heterogenous in design and quality, leaving it unclear whether the overall effect is statistically significant. As such, this paper investigated the relationship between sleep disturbances and AB burden by meta-analytically integrating reported correlations that have been published to date. Results revealed that higher levels of cerebral AB (lower AB42/40 ratios) were related to shorter sleep durations, highlighting the importance of total sleep time in supporting the clearance of AB during slow-wave sleep. Herein we also controlled for heterogeneity in the included studies by conducting several moderator analyses, showing an important role for age, sex, cognitive impairment, sleep disorders, and education in influencing the associations between sleep disturbances and AB.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50187063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarkers in Parkinson’s disease: A state of the art review 帕金森病的生物标志物：最新进展

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-09-09 DOI: 10.1016/j.bionps.2023.100074

Kyla Y. Yamashita , Sweta Bhoopatiraju , Bret D. Silverglate , George T. Grossberg

引用次数: 0

Molecular biomarkers and cognitive impairment in multiple sclerosis: A review 多发性硬化症的分子生物标志物与认知障碍：综述

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-09-29 DOI: 10.1016/j.bionps.2023.100077

Sara Esmaeili , Ahmed Z. Obeidat , Aram Zabeti

{"title":"Molecular biomarkers and cognitive impairment in multiple sclerosis: A review","authors":"Sara Esmaeili , Ahmed Z. Obeidat , Aram Zabeti","doi":"10.1016/j.bionps.2023.100077","DOIUrl":"https://doi.org/10.1016/j.bionps.2023.100077","url":null,"abstract":"<div><p>Cognitive Impairment (CI) is one of the most common and devastating manifestations in patients with Multiple Sclerosis (MS), which directly impacts the quality of life (QOL) and increases the burden of the disease. Years ago, CI was underrated but recently has gained far more attention from scientists in this field. The baseline pathophysiology and exact brain changes leading to CI are yet to be known. Both inflammatory and neurodegenerative processes could be contributing to CI. As a result, the diagnosis of subtle changes, especially in the early phases of the disease, along with the detection of changes throughout the disease course, is of utmost challenging debate among healthcare providers. Conventional Imaging techniques and usual neuropsychiatric screening tests may not detect early CI, rendering some cases missed. Serum or cerebrospinal fluid biomarkers are promising surrogates to detect the CI in these patients. The field of biomarkers in MS is evolving, and growing evidence indicates its applicability in decision-making. In this review, we focused on serum and CSF biomarkers that correlate with the CI in MS. In the end, we briefly discussed the future path in this regard.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50187068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Abnormal level of VDR-associated lncRNAs in patients with multiple sclerosis 多发性硬化症患者vdr相关lncrna水平异常

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 DOI: 10.1016/j.bionps.2023.100082

Shahrokh Janamiri , Bashdar Mahmud Hussen , Shaghayegh Heidari , Mohammad Taheri , Solat Eslami , Mehdi Dadmehr , Soudeh Ghafouri-Fard , Somayeh Farahmand

{"title":"Abnormal level of VDR-associated lncRNAs in patients with multiple sclerosis","authors":"Shahrokh Janamiri , Bashdar Mahmud Hussen , Shaghayegh Heidari , Mohammad Taheri , Solat Eslami , Mehdi Dadmehr , Soudeh Ghafouri-Fard , Somayeh Farahmand","doi":"10.1016/j.bionps.2023.100082","DOIUrl":"https://doi.org/10.1016/j.bionps.2023.100082","url":null,"abstract":"<div><p>Long non-coding RNAs (lncRNAs) influence pathoetiology of multiple sclerosis (MS). We identified expression levels of three vitamin D receptor-associated lncRNAs, namely <em>SNHG6</em>, <em>SNHG16</em> and <em>LINC00346</em> in the blood of MS patients compared with healthy subjects. <em>SNHG6</em> level was significantly lower in MS cases compared with controls (expression ratio (ER) (95 % CI)= 0.39 (0.22–0.69), P = 0.0015) and in female patients compared with female controls (ER (95 % CI)= 0.28 (0.13–0.59), P = 0.0001). <em>SNHG16</em> was also under-expressed in total MS patients compared with controls (ER (95 % CI)= 0.24 (0.1–0.57), P = 0.0001). <em>LINC00346</em> level was lower in entire patients versus controls (ER (95 % CI)= 0.03 (0.009–0.09), P < 0.0001). Such down-regulation was also detected in patients of both sexes compared with corresponding controls (P = 0.0008 and <0.0001 for males and females, respectively). There was no difference in expressions of <em>SNHG6</em>, <em>SNHG16</em> and <em>LINC00346</em> between male and female patients. There was no remarkable correlation between expressions of <em>SNHG6</em>, <em>SNHG16</em> and <em>LINC00346</em> lncRNAs and age, disease duration, age at onset or EDSS. <em>LINC00346</em> had the AUC values of 0.84, 0.82 and 0.94 in differentiation of total MS patients from total controls, female patients from healthy females and male patients from healthy males, respectively. <em>SNHG6</em> could separate female patients from female controls with AUC of 0.79. Finally, female patients from female controls could be separated by <em>SNHG16</em> levels with AUC of 0.73. Taken together, these lncRNAs might be proposed as putative peripheral markers for MS.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666144623000229/pdfft?md5=6ce761ab08837a2fb19cc7130366ea23&pid=1-s2.0-S2666144623000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138484083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Carpenter-Strauss quest to save schizophrenia: How DSM shifted the construct from its historical core 卡朋特-施特劳斯拯救精神分裂症的探索:DSM如何从其历史核心转移结构

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-02-16 DOI: 10.1016/j.bionps.2023.100061

Brett A. Clementz

{"title":"The Carpenter-Strauss quest to save schizophrenia: How DSM shifted the construct from its historical core","authors":"Brett A. Clementz","doi":"10.1016/j.bionps.2023.100061","DOIUrl":"10.1016/j.bionps.2023.100061","url":null,"abstract":"<div><p>During the 1960 s and 1970 s, questions about the validity of psychiatric diagnoses challenged psychiatry's respectability. Robert Spitzer and the DSM-III project hoped to rescue psychiatry by fixing its diagnoses. However, their choices regarding the schizophrenia diagnosis perhaps hampered psychosis research for 40 years. The defining characteristics of psychosis are perceptions, thoughts, and actions that do not comport with socially shared experience. For Kraepelin and Bleuler, the core features of a schizophrenia-like psychosis syndrome were disturbances of affect, self, and volition. John Wing and the International Pilot Study of Schizophrenia (IPSS) favored the theory of Kurt Schneider and his symptoms of first-rank importance for diagnosing schizophrenia. They reconceptualized schizophrenia as a reality distortion diagnosis. Will Carpenter and John Strauss, using IPSS data, showed that schizophrenia was most like an affect-self-volition disturbance syndrome and that depending on reality distortions for a schizophrenia diagnosis was incompatible with the evidence. Nevertheless, schizophrenia in DSM-III and DSM-IV was championed by John Wing and embraced by the DSM framers. Outcomes from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) are consistent with Carpenter and Strauss's concern that switching from a Kraepelin-Bleuler core to reality distortion was an error. B-SNIP found, replicated, cross- and externally validated neurobiologically distinctive subgroups called psychosis Biotypes. The main clinical characteristics differentiating the Biotypes are thought disturbances, lack of spontaneous speech, and low involvement in social and occupational activities. Psychosis research and clinical care might be different today if Spitzer and the DSM-III framers had made a different choice and listened to Carpenter and Strauss.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666144623000011/pdfft?md5=01f537a9eb7de525543d98ed0fd18575&pid=1-s2.0-S2666144623000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43258766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

COVID-19 and mental health risks in children: A role for biomarkers of inflammation, stress and the gut-brain axis COVID-19与儿童心理健康风险:炎症、压力和肠脑轴生物标志物的作用

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-11-22 DOI: 10.1016/j.bionps.2023.100080

Destini Carmichael , Laura M. Prichett , Tina Kumra , Yong Zeng , Andrea S. Young , Robert H. Yolken , Emily G. Severance

{"title":"COVID-19 and mental health risks in children: A role for biomarkers of inflammation, stress and the gut-brain axis","authors":"Destini Carmichael , Laura M. Prichett , Tina Kumra , Yong Zeng , Andrea S. Young , Robert H. Yolken , Emily G. Severance","doi":"10.1016/j.bionps.2023.100080","DOIUrl":"https://doi.org/10.1016/j.bionps.2023.100080","url":null,"abstract":"<div><p>Viral infections during childhood can increase susceptibilities to neurodevelopmental and psychiatric disorders. We are currently in the early years following a viral pandemic caused by the rapid evolution of highly transmissible, host-evading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here we place this virus and the disease it generates, Coronavirus Disease 2019 (COVID-19), in the context of inflammatory host phenotypes and psychosocial factors which exacerbate stress to the developing human nervous system. While exposures to pathogens and inflammation during neurodevelopment are well-studied risk factors in psychiatric research, the subtle effects on a child’s physiology of factors such as social isolation, food insecurity, and other social determinants of health are more difficult to identify and quantify. In this post-pandemic era, we have the unique opportunity to initiate in local community healthcare facilities, inclusive longitudinal studies to measure pandemic-mediated mental health outcomes in children of all races, ethnicities, genders, and other groups shaped by social, cultural, and as yet unidentified determinants. Toward this end, the identification of children in need of prompt psychiatric intervention may be accelerated by the use of biomarkers indicating COVID-19 infection status, inflammation, imbalances of the gut-brain axis, and acute and chronic stress. Especially promising are approaches combining these biomarkers with mental health screening tools such as the Child Behavior Checklist (CBCL) and the Epic Patient Healthcare Questionnaire 9 (PHQ9).</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666144623000205/pdfft?md5=ad8fce165076c6c39a520da858ca1593&pid=1-s2.0-S2666144623000205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138436903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarkers in multiple sclerosis: An update 多发性硬化症的生物标志物：最新进展

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-09-12 DOI: 10.1016/j.bionps.2023.100075

Jad Costa , Gabrielle Macaron , Karine J. Abou Khaled

引用次数: 0

Altered brain dopamine metabolism is a trait marker for bipolar disorder 大脑多巴胺代谢改变是双相情感障碍的特征标志

Biomarkers in Neuropsychiatry Pub Date : 2023-12-01 Epub Date: 2023-09-30 DOI: 10.1016/j.bionps.2023.100078

Erik Pålsson , Carl Sellgren , Aurimantas Pelanis , Henrik Zetterberg , Kaj Blennow , Mikael Landén

{"title":"Altered brain dopamine metabolism is a trait marker for bipolar disorder","authors":"Erik Pålsson , Carl Sellgren , Aurimantas Pelanis , Henrik Zetterberg , Kaj Blennow , Mikael Landén","doi":"10.1016/j.bionps.2023.100078","DOIUrl":"https://doi.org/10.1016/j.bionps.2023.100078","url":null,"abstract":"<div><p>Pharmacological treatment, imaging, and neurochemistry studies identify altered dopamine signaling in bipolar disorder. Our previous work has shown higher concentration of homovanillic acid (HVA), the end metabolite of dopamine, in cerebrospinal fluid (CSF) from individuals with bipolar disorder compared to healthy controls. Here, we analyzed HVA concentrations from a follow-up visit in 103 adults with bipolar disorder and 57 controls from our first cohort. Further, we analyzed CSF monoamine metabolite concentrations in a second cohort of 152 adults with bipolar disorder and 55 controls. At the follow-up visit for the first cohort, HVA was higher in individuals with bipolar disorder (278 ± 102 nmol/L, p = 0.003) compared with controls (232 ± 83 nmol/L). In the second cohort, individuals with bipolar disorder had higher HVA (272 ± 97 nmol/L, p = 0.001) and lower 3-methoxy-4-hydroxyphenylglycol (MHPG, 40 ± 9 nmol/L, p = 0.002) concentrations than controls (HVA, 231 ± 71 nmol/L and MHPG, 45 ± 9 nmol/L). Baseline and follow-up measures of monoamine metabolites showed medium to high correlation to each other but did not predict course of illness. We failed to replicate the association of HVA concentration and psychotic symptoms but confirmed lower 5-hydroxyindoleacetic acid (5-HIAA) concentration in individuals treated with antidepressants. In conclusion, we confirmed high HVA concentration in CSF in patients with bipolar disorder compared to a control group. Previous work suggest that this is a feature shared with ADHD but distinct from schizophrenia and major depressive disorder. The role of increased HVA concentration in the course of illness in bipolar disorder remains unclear.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"9 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50187069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A narrative review and discussion of concepts and ongoing data regarding quantitative EEG as a childhood mood disorder biomarker 关于定量脑电图作为儿童情绪障碍生物标志物的概念和正在进行的数据的叙述性综述和讨论

Biomarkers in Neuropsychiatry Pub Date : 2023-06-01 Epub Date: 2022-12-21 DOI: 10.1016/j.bionps.2022.100060

Serhiy Y. Chumachenko , Molly McVoy

{"title":"A narrative review and discussion of concepts and ongoing data regarding quantitative EEG as a childhood mood disorder biomarker","authors":"Serhiy Y. Chumachenko , Molly McVoy","doi":"10.1016/j.bionps.2022.100060","DOIUrl":"https://doi.org/10.1016/j.bionps.2022.100060","url":null,"abstract":"<div><h3>Background</h3><p>As the need for prompt identification and management of childhood mood. disorders continues to grow, increasing interest has shifted towards potential objective. biomarkers. One modality that has shown promise as a biomarker has been quantitative electroencephalography or qEEG. In this review, we expand on our previous investigation into qEEG biomarker research for child mood disorders and potential challenges faced in ongoing development.</p></div><div><h3>Ongoing research into qEEG:</h3><p>Since our last systematic review, qEEG biomarker research of childhood major depressive disorder remained sparse, with only one novel awake qEEG investigation in children despite ongoing adult depression qEEG research. For bipolar disorder, previously identified qEEG researchers have continued investigation into Bipolar II diagnosis identification, Bipolar I versus II diagnostic discrimination, and general bipolar biomarker utilization.</p></div><div><h3>Challenges faced by qEEG:</h3><p>While the nature of qEEG as a data-driven, easily performed, and easily analyzable biomarker is promising, challenges to clinical utilization remain, including direct anatomical correlation and generation of patientfacing clinically tested and usable tools. However, preliminary general utilization of qEEG in clinical settings with childhood mood disorder has shown excellent efficacy, and ongoing research to address these limitations is feasible and ongoing.</p></div><div><h3>Conclusions</h3><p>While qEEG biomarker research in child mood disorders has remained slow, there is a clear need and strong ongoing potential for future investigations.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"8 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50190117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarkers in frontotemporal dementia: Current landscape and future directions 额颞叶痴呆的生物标志物:现状和未来方向

Biomarkers in Neuropsychiatry Pub Date : 2023-06-01 Epub Date: 2023-05-31 DOI: 10.1016/j.bionps.2023.100065

Abbott Gifford , Nathan Praschan , Amy Newhouse , Zeina Chemali

{"title":"Biomarkers in frontotemporal dementia: Current landscape and future directions","authors":"Abbott Gifford , Nathan Praschan , Amy Newhouse , Zeina Chemali","doi":"10.1016/j.bionps.2023.100065","DOIUrl":"10.1016/j.bionps.2023.100065","url":null,"abstract":"<div><p>Frontotemporal dementia (FTD) is one of the most common neurodegenerative diseases, encompassing a myriad of different, clinically distinct subtypes which all target the frontoinsular region. FTD is characterized by a decline in behavioral, language, and executive functions. Due to its proximity to similar diseases, both in symptomology and mechanism, FTD remains challenging to diagnose conclusively. As a result, searching for distinct biomarkers that allow clinicians to differentiate between FTD and other neurocognitive disorders is extremely important. This review examines studies published in the past decade to evaluate which current biomarkers are the most clinically viable and where future research might lead. Genetic screening for FTD, specifically the three most common mutations to the TDP-43, MAPT, and PGRN genes, show promising predictive ability and could help patients access treatment in the early stages of the disease. In addition, serum and CSF biomarkers can help clinicians track the disease process and show good specificity when differentiating between FTD, primary psychiatric disorders, and other neurodegenerative diseases, especially when coupled with imaging techniques such as MRI and PET. Lastly, recent advances in machine learning may allow future researchers and clinicians to comprehensively analyze FTD's biochemical and imaging fingerprint, leading to increasingly accurate and timely diagnosis. Further work must be focused on transitioning the understanding of FTD biomarkers from research to concrete tools available to clinicians and patients, with the hopes of advancing the quality of care available to those suffering from FTD.</p></div>","PeriodicalId":52767,"journal":{"name":"Biomarkers in Neuropsychiatry","volume":"8 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44262302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1