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OBJECTIVES@#To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.@*METHODS@#In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.@*RESULTS@#A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.@*CONCLUSIONS@#The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.
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Niño , Humanos , Biomarcadores , Exosomas , Proteínas de la Matriz Extracelular , Síndrome Mucocutáneo Linfonodular/diagnóstico , Estudios Prospectivos , Proteómica , Factor de von WillebrandRESUMEN
Netrin-1 may protect and repair the damage caused by cerebral infarction, in terms of inhibiting apoptosis and inflammatory, and promoting angiogenesis and axon regeneration, etc. Netrin-1 may associate with the pathogenesis and outcome of cerebral infarction. The application of Netrin-1 in clinic needs more researches.
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Notch signaling pathway is a highly conserved signaling pathway in evolution, which would be activated to play a role in apoptosis, angiogenesis, neurogenesis, immune inflammation and others after ischemia. After acupuncture for ischemic stroke, the expression of Notch signaling pathways related factors increase, which may play a role in neurogenesis, ischemic tolerance, apoptosis, angiogenesis, and so on.
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In the era of coronavirus disease 2019 (COVID-19) pandemic, imported COVID-19 cases pose great challenges to many countries. Chest CT examination is considered to be complementary to nucleic acid test for COVID-19 detection and diagnosis. We report the first community infected COVID-19 patient by an imported case in Beijing, which manifested as nodular lesions on chest CT imaging at the early stage. Deep Learning (DL)-based diagnostic systems quantitatively monitored the progress of pulmonary lesions in 6 days and timely made alert for suspected pneumonia, so that prompt medical isolation was taken. The patient was confirmed as COVID-19 case after nucleic acid test, for which the community transmission was prevented timely. The roles of DL-assisted diagnosis in helping radiologists screening suspected COVID cases were discussed.
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Adulto , Humanos , Masculino , Beijing , COVID-19/diagnóstico por imagen , Prueba de COVID-19/métodos , Infecciones Comunitarias Adquiridas/diagnóstico por imagen , Aprendizaje Profundo , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective To evaluate the effectiveness of single nucleotide polymorphism (SNP) genoty-ping in combination with identity by state (IBS) strategy in full sibling testing. Methods Thirty-five blood samples were collected from a four-generation family. Ninety autosomal SNPs were genotyped using Precision ID Identity Panel. The distribution of IBS scores for full siblings and other relationships were calculated and compared. The relationships were determined using Fisher discriminant function and threshold method, respectively. Results Based on family members and previous research, 44, 30, 111, 71 and 1 000 pairs of full siblings (FS), grandparent-grandchild (GG), uncle/aunt-nephew/niece (UN), first cousins (FC) and unrelated individuals (UI) were obtained, respectively. The average IBS scores were 148, 130, 132, 124 and 120, respectively. Except for the GG and UN pairs, the distribution differences among the other relationships had statistical significance (P<0.05). The false rates of Fisher discriminant function to determine relationships were 1.3%, 22.3%, 17.0% and 38.7% for FS, GG, UN and FC, respectively. Based on the simulation data, the thresholds t1=128 and t2=141 were recommended to determine full sibling relationships (the false rate ≤0.05%). Conclusion The 90 SNP genetic markers included in the Precision ID Identity Panel meet the testing requirements for full sibling relationships. The threshold method based on IBS has a relatively lower false rate and is more flexible.
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Humanos , Genotipo , Técnicas de Genotipaje/métodos , Polimorfismo de Nucleótido Simple/genética , HermanosRESUMEN
Objective To evaluate the effect of 56 ancestry informative single nucleotide polymorphism (aiSNP) genetic markers in the ForenSeqTM DNA Signature Prep Kit on ancestry inference. Methods A total of 85 samples from five populations including Hebei Han population, Inner Mongolia autonomous region Mongolian population, Tibet autonomous region Tibetan population, Xinjiang Uygur autonomous region Uygur population and Nigerian population were collected. The library was constructed with the ForenSeqTM DNA Signature Prep Kit and sequencing was performed based on the MiSeq FGx Forensic Genomics System. Using universal analysis software (UAS) of ForenSeqTM, principal component analysis (PCA), Structure and likelihood ratio method was used on the genotyping data of 56 aiSNP markers, respectively, and the genetic relationships between populations and inference of the origin of ancestors were analyzed. Results Among the five populations tested, the four ethnic populations in China (Hebei Han population, Inner Mongolia autonomous region Mongolian population, Tibet autonomous region Tibetan population and Xinjiang Uygur autonomous region Uygur population) could be significantly distinguished from Nigerian population. Xinjiang Uygur autonomous region Uygur individuals were shown as having mixed origins of ancestors and could be distinguished from the other three Chinese populations. However, the other three populations in China (Hebei Han population, Inner Mongolia autonomous region Mongolian population and Tibet autonomous region Tibetan population) could not be effectively distinguished by the system. Conclusion The 56 aiSNP markers in the ForenSeqTM DNA Signature Prep Kit can make accurate ancestry inference from the intercontinental level, but it is not yet able to distinguish between Chinese subpopulations.
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Humanos , Pueblo Asiatico/genética , China , ADN , Dermatoglifia del ADN , Etnicidad/genética , Genética Forense/métodos , Genética de Población , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Polimorfismo de Nucleótido SimpleRESUMEN
Objective: To study the chemical components from Mongolian medicinal materials Ramulus syringae (the peeled roots and branches of Syringa pinnatifolia). Methods: The compounds were purified by column chromatography on silica gel, ODS, and Sephadex LH-20. Their structures were elucidated on the basis of spectroscopic methods. Results: Twenty-one compounds were isolated from R. syringae and their structures were identified as O-ethylcubebin (1), pinnatifone B (2), 3β-O-acetyl-11α,12α- epoxy-oleanan-28,13β-olide (3), coniferyl aldehydel (4), (8R,8’R,9S)-cubebin (5), isovanillic acid (6), (+)-dihydrocubebin (7), 6,10- eposoy-4α-hydroxy guaiane (8), (+)-1β,4β,6α-trihydroxyl-eudesmane (mucrolidin, 9), acutissimalignan B (10), 2-piperonylidene-3- piperonyl-1,4-butanediol (11), 4,4’-dihydroxy-3,3’,9’-triMethoxy-9,9’-epoxylignan (12), 2β-hydroxy-α-cadinol (13), cadinane-4β,5α, 10α-triol (14), larixnaphthanoe (15), lariciresinol (16), 4,4’9-trihydroxy-3,3’-dimethoxy-9,9’-epoxylignan (17), (-)-secoisolariciresino- 9,9’-acetonide (18), berchemol (19), daucosterol (20), and ecoisolariciresinol (21). Conclusion: Compounds 1, 7, 8, 9, 10, 13, 14, and 18 are isolated from the genus Syringa for the first time. Compounds 3 and 20 are isolated from S. pinnatifolia for the first time.
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<p><b>OBJECTIVE</b>To investigate the apoptotic effects of Hsp90 selective inhibitor 17-AAG on human leukemia HL-60 and NB4 cells and analyse its possible mechanism.</p><p><b>METHODS</b>CCK-8 assay was used to quantify the growth inhibition of cells after exposure to 17-AAG for 24 hours. Flow cytometrve with annexin V/propidium iodide staining was used to detect apoptosis of leukemia cells. Then Western blot was used to detect the activation of apoptosis related protein caspase-3 and PARP level. Gene expression profile of NB4 cells treated with 17-AAG was analyzed with real-time PCR arrays.</p><p><b>RESULTS</b>The inhibition of leukemia cell proliferation displayed a dose-dependent manner. Annexin V assay, cell cycle analysis and activation of PARP demonstrate that 17-AAG induced apoptosis leukemia cells. Real-time PCR array analysis showed that expression of 56 genes significantly up-regulated and expression of 23 genes were significantly down-regulated after 17-AAG treatment.</p><p><b>CONCLUSION</b>The 17-AAG can inhibit the proliferation and induce the apoptosis of leukemia cells. After leukemia cells are treated with 17-AAG, the significant changes of apoptosis-related genes occured, and the cell apoptosis occurs via activating apoptosis related signaling pathway.</p>
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Humanos , Apoptosis , Benzoquinonas , Farmacología , Caspasa 3 , Metabolismo , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Células HL-60 , Proteínas HSP90 de Choque Térmico , Lactamas Macrocíclicas , Farmacología , Leucemia , Metabolismo , Poli(ADP-Ribosa) Polimerasas , Metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , TranscriptomaRESUMEN
BACKGROUND: Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells. METHODS: SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool. RESULTS: LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC. CONCLUSIONS: LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589.
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Apoptosis/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Tumor de Wilms/patología , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Ratones , Ratones Desnudos , Panobinostat , ARN Largo no Codificante/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Two new sesquiterpenes, innatifolone A (1) and pinnatifolone B (2), along with 6 known compounds, furostan (3), isocalamendiol (4), pluviatolide (5), (8S,8'R,9S)-cubebin (6), 2-(4-hydroxy-3-methoxybenzyl)-3-(3,4-dimethoxybenzyl) tetrahydrofuran (7), and methyl 3-acetoxy-12-oleanen-28-oate (8), were isolated from Mongolian herb Syringa pinnatifolia.
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Medicamentos Herbarios Chinos , Química , Espectrometría de Masas , Estructura Molecular , Mongolia , Plantas Medicinales , Química , Syringa , QuímicaRESUMEN
Twenty-two compounds were isolated from the flowers of Scabiosa tschilliensis. Their structures were identified by spectroscopic methods as octacosanol (1), stearic acid (2), β-sitosterol (3), oleanolic acid (4), apigenin (5), luteolin (6), daucosterol (7), kaempferol-3-O-β-D-6-O-(p-hydroxycinnamoyl) -glucopyranoside (8), kaempferol-3-O-β-D- (3, 6-di-p-(hydroxycinnamoyl) -glucopyranoside (9), apigenin-7-O-β-D-glucopyranoside (10), luteolin-4'-O-β-D-glucopyranoside (11), apigenin-7-O-rutinoside (12), luteolin-7-O-β-D-glucopyranoside (13), apigenin-4'-O-β-D-glucopyranoside (14), caffeic acid methyl ester (15), loganin (16), adenosine (17), luteolin-6-C-β-D-glycopyranosyl (18), sweroside (19), sylvestrosides I (20), sylvestrosides II (21), urceolide (22). Among them, compounds 1, 2, 7-9, 12, 15, 17-18, 20-22 were isolated from the genus Scabiosa for the first time, and compounds 1-4, 6-9, 11-12, 14-22 were isolated from this plant for the first time. 13C-NMR data of 22 were reported for the first time.
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Dipsacaceae , Química , Medicamentos Herbarios Chinos , Química , Flores , Química , Estructura Molecular , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
AIM: To evaluate the effects induced by topical antiglaucomatous drugs, Travoprost eyedrops on tear film. METHODS: Eighteen patients ( 32 eyes ) with primary open-angle glaucoma or ocular hypertension were all treated with Travoprost eyedrops once every night. The symptom score, Schirmer's test ( S Ⅰ t ) , corneal fluorescein staining ( FL ) , tear film break - up time (BUT), were observed before the treatment and 1, 2 and 3mo after the treatment. RESULTS: The average symptom score, FL of all patients were 1. 34 ± 1. 56 and 0. 44 ± 0. 73 before the treatment, and 2. 75±1. 63, 1. 08±0. 84; 5. 10±1. 68, 1. 53±0-67;6. 33±1. 40, 1. 98±0. 50 respectively after 1, 2 and 3mo of the treatment. There was significant increase in symptom score and FL after the treatment for 1, 2 and 3mo (P=0. 00). The average BUT, SⅠt of all patients were (7. 76±0. 92s), (8. 47±2. 73mm/5min) before the treatment, and (7. 08±1. 15s), (7. 73±3. 44mm/5min);(5-59±1. 33s), (6. 82±3. 05mm/5min); (4. 29±1. 87s), (6-04±3. 15mm/5min) respectively after 1, 2 and 3mo of the treatment. There was significant decrease in BUT and ST after the treatment for 1, 2 and 3mo (P=0. 00). CONCLUSION: Travoprost eyedrops can obviously aggravate patients’ corneal irritation after treatment. Our results show abnormal decreased tear secretion and stability of tear film induced by Travoprost eyedrops over the short term.
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<p><b>OBJECTIVE</b>To explore the association between the common variations of TET2 (rs7679673, A), MTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes and prostate cancer (Pca) risk in Chinese population in Beijing, and to understand the relationship between genotypes and phenotypes including clinical characteristics and life style, etc. in patients with prostate cancer.</p><p><b>METHODS</b>Based on a case-control study, 124 patients with prostate cancer and 138 age-matched control subjects were recruited. Information of clinical phenotype and life style, etc. in the prostate cancer patients was collected. We compared the differences of allele and genotype frequencies of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) gene expressions between the two groups for the allele and genotype frequencies, and explored the relationship between different genotypes and clinical features such as patient age, BMI, Gleason score, PSA level and tumor stage, by Chi-square test in patients with PCa. Multifactor dimensionality reduction was used to detect the gene-gene interactions.</p><p><b>RESULTS</b>The FAM84B (rs12543663, C) C carriers frequency had significant difference between the case group and the control group (χ(2) = 3.980 P = 0.046; OR = 1.883; 95%CI = 1.006-3.526). The allele and genotype frequencies of TET2 gene (rs7679673, A) and LMTK2 gene (rs6465657, T) were not significantly different between the case group and the control group (P > 0.05). Analysis of the genotypes and clinical phenotypes showed that the genetic type of FAM84B C carriers [CX (CC + CA)] were significantly associated with cancer stage (χ(2) = 9.585; P = 0.002; OR = 3.740; 95%CI = 1.580 - 8.853). Association between three loci and 12 kind of relevant outcomes was found in TET2 A carriers and the smoking and drinking patients (all P < 0.05). Significant correlation was also found between LMTK2 (rs6465657, T) TX carriers and surgery (χ(2) = 8.612; P = 0.003; OR = 0.174; 95%CI 0.049 - 0.620). No significant correlation was seen with other covariates (P > 0.05). Dendrogram analysis among the three loci showed that the best model consisted of the three sites (P = 0.0270), cross validation consistency: 10/10, and testing balanced accuracy: 0.5120. There may be gene-gene interaction among TET2 (rs7679673, A), LMTK2 (rs6465657, T), and FAM84B (rs12543663, C).</p><p><b>CONCLUSIONS</b>There may be obvious association of FAM84B (rs12543663, C) gene with prostate cancer risk and the stages, and the synergistic effects of TET2 (rs7679673, A), LMTK2 (rs6465657, T) and FAM84B (rs12543663, C) genes may have an association with prostate cancer risk in Chinese population.</p>
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Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Consumo de Bebidas Alcohólicas , Alelos , Pueblo Asiatico , Genética , Estudios de Casos y Controles , Proteínas de Unión al ADN , Genética , Metabolismo , Regulación Neoplásica de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Proteínas de la Membrana , Genética , Metabolismo , Proteínas de Neoplasias , Genética , Metabolismo , Estadificación de Neoplasias , Fenotipo , Neoplasias de la Próstata , Genética , Metabolismo , Patología , Proteínas Serina-Treonina Quinasas , Genética , Metabolismo , Proteínas Proto-Oncogénicas , Genética , Metabolismo , Factores de Riesgo , FumarRESUMEN
<p><b>OBJECTIVE</b>To investigate the association of prostate cancer (PCa) with PDLIM5 (rs17021918, T), SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) in Chinese men.</p><p><b>METHODS</b>We included 124 PCa patients and 138 normal controls in this study, compared the alleles and genotypes of PDLIM5 (rs17021918, T) , SLC22A3 (rs9364554, C) and NKX3-1 (rs1512268, A) of the two groups, and explored the association of each of the genes with the age, body mass index (BMI), Gleason score, PSA level and tumor stage of the patients. We analyzed the gene-gene interaction using the multifactor dimensionality reduction method (MDR).</p><p><b>RESULTS</b>There were no statistically significant differences in the frequency distribution of the risk alleles and genotypes of PDLIM5, SLC22A3 and NKX3-1 between the case and control groups (P > 0.05), nor were the three gene loci significantly associated with the age, Gleason score, PSA level and pathological grade of the PCa patients (CP < 0.05). MDR analysis showed no interaction between PDLIM5 and NKX3-1, but tree-diagram analysis revealed a possible synergistic action of the two polymorphism loci.</p><p><b>CONCLUSION</b>PCa might not be associated with PDLIM5 (rs17021918,T), SLC22A3 (rs9364554,C) and NKX3-1 (rs1512268,A) in Chinese men. However, PDLIM5 and NKX3-1 might have a synergistic action on the risk PCa.</p>