biomarker

摘要： Mild cognitive impairment(MCI)is a prodrome of Alzheimer’s disease pathology.Cognitive impairment patients often have a delayed diagnosis because there are no early symptoms or conventional diagnostic methods.Exosomes play a vital role in cell-to-cell communications and can act as promising biomarkers in diagnosing diseases.This study was designed to identify serum exosomal candidate proteins that may play roles in diagnosing MCI.Mass spectrometry coupled with tandem mass tag approach-based non-targeted proteomics was used to show the differentially expressed proteins in exosomes between MCI patients and healthy controls,and these differential proteins were validated using immunoblot and enzyme-linked immunosorbent assays.Correlation of cognitive performance with the serum exosomal protein level was determined.Nanoparticle tracking analysis suggested that there was a higher serum exosome concentration and smaller exosome diameter in individuals with MCI compared with healthy controls.We identified 69 exosomal proteins that were differentially expressed between MCI patients and healthy controls using mass spectrometry analysis.Thirty-nine exosomal proteins were upregulated in MCI patients compared with those in control patients.Exosomal fibulin-1,with an area under the curve value of 0.81,may be a biomarker for an MCI diagnosis.The exosomal protein signature from MCI patients reflected the cell adhesion molecule category.In particular,higher exosomal fibulin-1 levels correlated with lower cognitive performance.Thus,this study revealed that exosomal fibulin-1 is a promising biomarker for diagnosing MCI.

摘要： Microglia are resident immune cells in the central nervous system. During the pathogenesis of Alzheimer’s disease, stimulatory factors continuously act on the microglia causing abnormal activation and unbalanced phenotypic changes;these events have become a significant and promising area of research. In this review, we summarize the effects of microglial polarization and crosstalk with other cells in the central nervous system in the treatment of Alzheimer’s disease. Our literature search found that phenotypic changes occur continuously in Alzheimer’s disease and that microglia exhibit extensive crosstalk with astrocytes, oligodendrocytes, neurons, and penetrated peripheral innate immune cells via specific signaling pathways and cytokines. Collectively, unlike previous efforts to modulate microglial phenotypes at a single level, targeting the phenotypes of microglia and the crosstalk with other cells in the central nervous system may be more effective in reducing inflammation in the central nervous system in Alzheimer’s disease. This would establish a theoretical basis for reducing neuronal death from central nervous system inflammation and provide an appropriate environment to promote neuronal regeneration in the treatment of Alzheimer’s disease.

摘要： Previous studies have shown that ulnar nerve compound muscle action potential recorded by the conventional“belly-tendon”montage does not accurately and completely reflect the action potential of the ulnar nerve dominating the abductor digiti minimi muscle due to the effects of far-field potentials of intrinsic hand muscles.A new method of ulnar nerve compound muscle action potential measurement was developed in 2020,which adjusts the E2 electrode from the distal tendon of the abductor digitorum to the middle of the back of the proximal wrist.This new method may reduce the influence of the reference electrode and better reflect the actual ulnar nerve compound muscle action potential.In this prospective cross-sectional study,we included 64 patients with amyotrophic lateral sclerosis and 64 age-and sex-matched controls who underwent conventional and novel ulnar nerve compound muscle action potential measurement between April 2020 and May 2021 in Peking University Third Hospital.The compound muscle action potential waveforms recorded by the new montage were unimodal and more uniform than those recorded by traditional montage.In the controls,no significant difference in the compound muscle action potential waveforms was found between the traditional montage and new montage recordings.In amyotrophic lateral sclerosis patients presenting with abductor digiti minimi spontaneous activity and muscular atrophy,the amplitude of compound muscle action potential-pE2 was significantly lower than that of compound muscle action potential-dE2(P<0.01).Using the new method,damaged axons were more likely to exhibit more severe amplitude decreases than those measured with the traditional method,in particular for patients in early stage amyotrophic lateral sclerosis.In addition,the decline in compound muscle action potential amplitude measured by the new method was correlated with a decrease in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores.These findings suggest that the new ulnar nerve compound muscle action potential measurement montage reduces the effects of the reference electrode through altering the E2 electrode position,and that this method is more suitable for monitoring disease progression than the traditional montage.This method may be useful as a biomarker for longitudinal follow-up and clinical trials in amyotrophic lateral sclerosis.

摘要： Crude oil and source rock samples from one of the main oilfields of the Abadan Plain, Zagros, Iran were analyzed geochemically. Rock-Eval pyrolysis was conducted on Kazhdumi(Upper Cretaceous) and Gadvan(Lower Cretaceous) formations, which are the probable source rocks for the oil in the region. The results indicated that the Kazhdumi Formation can be classified as a fair-to-excellent source rock, while the Gadvan Formation can be identified as having poor-to-good source rock in the basin. Based on the cross-plots of HI versus OI and S2 versus TOC, types Ⅱ and Ⅲ kerogen were identified from studied source samples in the area. Determination of the main fraction percentages of the Sarvak and Fahliyan crude oils represented that the oils from the Sarvak reservoir are paraffinic-naphthenic and aromaticintermediate, whilst that from the Fahliyan reservoir is paraffinic and paraffinic-naphthenic. Biomarker ratios of the saturated fractions of oil from both reservoirs indicate that the source rocks formed in reducing marine environments with carbonate-shale lithology. Furthermore, biomarker data helped to distinguish the degree of biodegradation in the studied oils. According to geochemical analysis, oil samples from the Fahliyan reservoir were generated at a higher thermal maturity than the Sarvak reservoir samples.

摘要： Esophageal cancer(EC)is a malignant cancer that still has a poor prognosis,although its prognosis has been improving with the development of multidisciplinary treatment modalities such as surgery,chemotherapy and radiotherapy.Therefore,identifying specific molecular markers that can be served as biomarkers for the prognosis and treatment response of EC is highly desirable to aid in the personalization and improvement of the precision of medical treatment.Sirtuins are a family of nicotinamide adenine dinucleotide(NAD+)-dependent proteins consisting of seven members(SIRT1-7).These proteins have been reported to be involved in the regulation of a variety of biological functions including apoptosis,metabolism,stress response,senescence,differentiation and cell cycle progression.Given the variety of functions of sirtuins,they are speculated to be associated in some manner with cancer progression.However,while the role of sirtuins in cancer progression has been investigated over the past few years,their precise role remains difficult to characterize,as they have both cancer-promoting and cancer-suppressing properties,depending on the type of cancer.These conflicting characteristics make research into the nature of sirtuins all the more fascinating.However,the role of sirtuins in EC remains unclear due to the limited number of reports concerning sirtuins in EC.We herein review the current findings and future prospects of sirtuins in EC.

摘要： Most hematological cancer-related relapses and deaths are caused by metastasis;thus,the importance of this process as a target of therapy should be considered.Hematological cancer is a type of cancer in which metabolism plays an essential role in progression.Therefore,we are required to block fundamental metastatic processes and develop specific preclinical and clinical strategies against those biomarkers involved in the metabolic regulation of hematological cancer cells,which do not rely on primary tumor responses.To understand progress in this field,we provide a summary of recent developments in the understanding of metabolism in hematological cancer and a general understanding of biomarkers currently used and under investigation for clinical and preclinical applications involving drug development.The signaling pathways involved in cancer cell metabolism are highlighted and shed light on how we could identify novel biomarkers involved in cancer development and treatment.This review provides new insights into biomolecular carriers that could be targeted as anticancer biomarkers.

摘要： The mdx mouse is a model of Duchenne muscular dystrophy(DMD),a fatal progressive muscle wasting disease caused by dystrophin deficiency,and is used most widely in preclinical studies.Mice with dystrophin deficiency,however,show milder muscle strength phenotypes than humans.In human,the introduction of a sandwich enzyme-linked immunosorbent assay(ELISA)kit revealed a more than 700-fold increase in titin N-terminal fragment levels in the urine of pediatric patients with DMD.Notably,the urinary titin level declines with aging,reflecting progression of muscle wasting.In mouse,development of a highly sensitive ELISA kit has been awaited.Here,a sandwich ELISA kit to measure titin N-terminal fragment levels in mouse urine was developed.The developed kit showed good linearity,recovery,and repeatability in measuring recombinant or natural mouse titin N-terminal fragment levels.The titin N-terminal fragment concentration in the urine of mdx mice was more than 500-fold higher than that of normal mice.Urinary titin was further analyzed by extending the collection of urine samples to both young(3-11 weeks old)and aged(56-58 weeks old)mdx mice.The concentration in the young group was significantly higher than that in the aged group.It was concluded that muscle protein breakdown is active and persistent in mdx mice even though the muscle phenotype is mild.Our results provide an opportunity to develop DMD treatments that aim to alleviate muscle protein breakdown by monitoring urinary titin levels.

摘要： Mesoproterozoic marine organic-rich rocks are widely distributed in the North China Craton,include the Gaoyuzhuang(GYZ),the Hongshuizhuang(HSZ),and the Xiamaling(XML)formations.According to the T;value and isomerisation ratio of C;homohopanes,the XML,HSZ,and GYZ samples were in low mature,mature and high mature stage,respectively.Biomarker distribution in extractable organic matter(EOM)of three Mesoproterozoic organic-rock samples in different maturity were analysed to reveal the organic precursor and preservation pathway of in the Mesoproterozoic Combined with gold-tube pyrolysates of three Mesoproterozoic samples,it could further illuminate the chemical composition of Mesoproterozoic kerogen,given excluding.The results indicated that the three formations were all deposited under reducing condition and their organic precursors mainly were some aquatic organisms.High content of rearranged hopanes was detected in EOM of XML and HSZ samples,whereas they were relatively low in the high mature GYZ sample.Contrast to that in EOM,the relative concentration of rearranged hopanes sharply decreased in the gold-tube pyrolysates of the XML kerogen,then slightly increased but was still significantly lower than the EOM of XML sample,which indicated that catalysis of clay minerals in the early diagenesis only changed the chemical composition of the unstable functional groups of the kerogen during the preservation.Due to the thriving heterotrophic microbes and low sink rate of particulate organic matter during the Mesoproterozoic,primary producers suffered extensive degradation during sinking process,only some resistant biopolymers lacking of lipid compounds survived from heterotrophic degradation,while heterotrophic microbes contained more proportion of organic precursors.Abundant pristane(Pr)and phytane(Ph)were only released in high mature stage because of the protection of the macromolecular structure of resistant biopolymers which prevented biomarkers from being altered by the thermal stress.The absence of 13α(n-alkyl)-tricyclic terpanes in the high matured hydrocarbon products also indicated the different precursors between different parts of Mesoproterozoic kerogen.The evolution of the biomarker composition and content of Mesoproterozoic kerogen showed some special characteristics differing from those of Phanerozoic kerogen.The total concentrations of hopanes displayed with an order of low mature stage>high mature stage>mature stage.Relative content of rearranged hopanes in the hydrocarbon generated in high mature stage was significantly lower than that in the low maturity stage.The ratios of Pr/n-C_(17) and Ph/n-C_(18) increased with thermal maturity,and the ratio of nC_(21-)/nC_(22+) decreased in the high maturity stage,thus displaying another order of mature stage>high maturity stage>low maturity stage.The unique preservation pathway of Mesoproterozoic organisms was attributed to the special evolution characteristics of biomarker distributions,which should be considered in the Mesoproterozoic marine environment and biological studies.

摘要： BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.

摘要： BACKGROUND Emerging evidence links gut microbiota to various human diseases including colorectal cancer(CRC)initiation and development.However,gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet,especially in a Chinese cohort.AIM To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis.METHODS We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy controls.The patients were followed up by regular examination to determine whether tumors recurred.Triplet-paired samples from on-tumor,adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA sequencing.Next,we carried out bioinformatic analyses,Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient prognosis.RESULTS We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis.A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis,including Anaerotruncus,Bacteroidales,Coriobacteriaceae,Dialister,Eubacterium,Fusobacterium,Filifactor,Gemella,Haemophilus,Mogibacteriazeae,Pyramidobacter,Parvimonas,Porphyromonadaceae,Slackia,Schwartzia,TG5 and Treponema.CONCLUSION Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.

摘要： 本发明提供一种肾癌血液生物标志物的检测方法及试剂盒。具体地说，本发明涉及一种对肾癌血液生物标志物NNMT、LCP1及NM23A全部进行检测的方法及试剂盒，这些检测结果能由医师之类的医疗专家有效地用来判断肾癌罹患与否、肾癌发展程度、肾癌治疗经过，尤其是能够有效地适用于肾癌的早期诊断、肾细胞癌类型中占大多数的透明细胞型肾细胞癌的诊断。

摘要： 本发明提供一种肾癌血液生物标志物的检测方法及试剂盒。具体地说，本发明涉及一种对肾癌血液生物标志物NNMT、LCP1及NM23A全部进行检测的方法及试剂盒，这些检测结果能由医师之类的医疗专家有效地用来判断肾癌罹患与否、肾癌发展程度、肾癌治疗经过，尤其是能够有效地适用于肾癌的早期诊断、肾细胞癌类型中占大多数的透明细胞型肾细胞癌的诊断。

摘要： 本发明涉及造血干细胞移植技术领域，且公开了一种基于aGVHD biomarker的非复发死亡风险监测模型，所述通过动态监测病人群体(199例，一年内的非复发死亡约占12％)不同时间点的aGVHD biomarker指标(sST2，REG3α)。计算病人移植后100天内每个检测时间点sST2和REG3α之间的距离值(value)，选取检测时间点中sST2和REG3α距离值达到最大时的aGVHD biomarker作为病人最坏情况的指标，建立模型数据集。该基于aGVHD biomarker的非复发死亡风险监测模型，通过建立分层标准，对病人进行风险分组，其180天非复发死亡的累积发生率为：低风险(2.38％)vs中风险(16.67％)vs高风险(52.0％)，分层结果优于已有研究[5](初始治疗时aGVHD biomarker分组：低风险(6％)vs中风险(20％)vs高风险(49％))。

摘要： 本发明涉及结合症状及biomarker信息的用于aGVHD病人精准风险分层的方法，包括以下步骤：选取多中心200例出现aGVHD症状的患者，其中非复发死亡约占15％,作为观测样本；通过Luminex平台检测步骤1)病人群体出现aGVHD症状时的biomarker(sST2，REG3α)指标。该结合症状及biomarker信息的用于aGVHD病人精准风险分层的方法，将病人出现aGVHD症状时(onset)的biomarker信息与基于症状轻重度的临床分级信息(I‑IV)相结合，对aGVHD病人进行非复发死亡风险精细划分，划分结果显示，临床症状表现为轻度(I‑II)的aGVHD病人中有21％(33/159)为非复发死亡高风险，临床症状表现为重度(III‑IV)的aGVHD病人中有24％为非复发死亡低风险，本发明在现有aGVHD治疗标准的基础上，充分发挥了biomarker信息对非复发死亡的分层价值，更具临床应用和指导意义。

摘要： 本发明涉及造血干细胞移植技术领域，且公开了一种基于aGVHDbiomarker的一线糖皮质激素治疗反应预测模型，其特征在于，包括以下步骤：通过Luminex平台监测aGVHD病人一线糖皮质激素治疗一周后的aGVHDbiomarker指标(sST2，REG3α)，作为基本数据条；将上述病人的基本数据条以及aGVHD发生时是否为重度与临床aGVHD一线糖皮质激素治疗反应进行关联，并采用逻辑回归技术，建立aGVHD一线糖皮质激素耐药/依赖预测模型。该基于aGVHDbiomarker的一线糖皮质激素治疗反应预测模型，通过建立机器学习模型，对发生aGVHD病人一线糖皮质激素治疗后是否发生激素抵抗/依赖进行预测及分层，为临床决策提供参考。

摘要： 本发明公开了一种基于aGVHD biomarker的重度肠道aGVHD模型的方法，属于造血干细胞移植技术领域，包括aGVHD biomarker指标监测及数据筛选与分组、单个重度肠道aGVHD模型训练、多模型融合、重度肠道aGVHD模型性能前瞻性验证的四个步骤。该基于aGVHD biomarker的重度肠道aGVHD模型的方法，通过建立机器学习模型，采用多模型融合技术对病人发生重度肠道aGVHD的严重程度进行评估，效果优于单个肠道aGVHD模型，对病人发生肠道aGVHD严重程度进行精准划分，为临床决策提供指导；同时仅需检测血清中aGVHD biomarker指标，避免了例如内窥镜检查和肠粘膜活检等的肠道aGVHD常规诊断方法给病人带来的强烈不适感，更适应于中国病人群体。

摘要： 本发明公开了一种用于真实世界数据的biomarker预测性研究方法，涉及造血干细胞移植技术领域。S1、biomarker指标监测及数据筛选与分组，动态监测真实世界病人群体重要时间点的biomarker指标；S2、基于sST2或REG3α峰值浓度进行风险分层，选取病人移植后100天内sST2、REG3α峰值浓度作为病人最坏情况的指标，并与病人的长期预后(生存、非复发死亡)进行统计关联；S3、动态监测病人风险分层变化及趋势。该用于真实世界数据的biomarker预测性研究方法，本发明更适应于真实世界数据，本发明摆脱了研究结论对具体检测时间点的依赖，更具临床参考性，本发明可动态监测病人所处的风险状态和趋势，便于医生随时关注和及时跟进病人的风险变化。

摘要： 本发明属于造血干细胞移植领域；本发明公开了一种基于aGVHD biomarker的风险分层及监测方法，包括以下步骤，S1：aGVHD biomarker指标监测及病人群体分组；S2：模型训练；S3：重度综合、肠道aGVHD风险分层；S4：动态监测病人风险分层变化及趋势；本发明采用模型融合技术，对病人进行重度综合、肠道aGVHD的低、中、高风险分层；可动态监测不同时间点病人的aGVHD biomarker指标、风险分层状态及变化趋势，为临床决策提供参考；相对应现有的技术本发明更适应于中国病人群体。