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1.
Protein & Cell ; (12): 695-716, 2021.
Article in English | WPRIM | ID: wpr-888726

ABSTRACT

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

2.
Chinese Journal of Radiology ; (12): 314-317, 2020.
Article in Chinese | WPRIM | ID: wpr-868284

ABSTRACT

Objective:To investigate the initial high resolution CT (HRCT) manifestations and clinical features of imported COVID-19 in Guangzhou.Methods:A retrospective analysis of 91 COVID-19 patients admitted to the Guangzhou Eighth People's Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years,then their clinical features and HRCT characteristics were analyzed.Results:The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry cough in 39 cases). The first time HRCT showed that 24 cases with COVID-19 were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung.Conclusion:The initial images of COVID-19 in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of COVID-19 patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.

3.
Protein & Cell ; (12): 809-824, 2020.
Article in English | WPRIM | ID: wpr-880897

ABSTRACT

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.


Subject(s)
Animals , Disease Models, Animal , Female , Gene Editing , Humans , Lamin Type A/metabolism , Macaca fascicularis , Progeria/pathology
4.
Journal of Experimental Hematology ; (6): 1904-1911, 2020.
Article in Chinese | WPRIM | ID: wpr-879991

ABSTRACT

OBJECTIVE@#To investigate the clinical efficacy of ALL-2005 and ALL-2009 regimen and factors influencing prognosis of newly diagnosed ALL patients aged between 10-18 years old to provide some reference for clinical diagnosis and treatment.@*METHODS@#The clinical data including baseline clinical characteristics, induction chemotherapy effect, long-term clinical efficacy, recurrence rate and mortality of induction therapy of 119 newly diagnosed ALL patients aged between 10-18 years old from January 2008 to December 2015 were analyzed retrospectively, and the influencing factors of clinical prognosis were evaluated by univariate and multivariate analysis.@*RESULTS@#The complete remission rate at the 5th week after induction therapy was not significantly different between ALL-2005 and ALL-2009 regimen groups (P>0.05). The cumulative event-free survival rate and overall survival rate of 119 cases after 5-year follow-up were (63.41±3.65)% and (68.95±4.01)% respectively, and after 7-year follow-up were (61.86±3.72)% and (67.22±3.59)% respectively. The cumulative event-free survival rate and overall survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P>0.05). The total recurrence rate, extramedullary recurrence rate, recurrence time and survival rate were not significantly different between ALL-2005 and ALL-2009 regimen groups (P>0.05). The survival rate of extramedullary recurrence group was significantly higher than bone marrow recurrence group (P<0.05). The survival rate in late term recurrence group was significantly higher than in early term recurrence group (P<0.05). The mortality of ALL-2005 regimens was not significantly different from that of ALL-2009 regimen group (P>0.05). Univariate analysis showed that age, sex, induction therapy, risk and fusion gene all were the factors influencing clinical prognosis (P<0.05). Multivariate analysis by Cox regression model showed that male, non-remission after induction therapy and high risk were the independent risk factors for poor prognosis in patients (P<0.05). The survival rate of patients with BCR-ABL@*CONCLUSION@#The survival rate of newly diagnosed ALL patients aged between 10-18 years old treated with ALL-2009 regimen was slightly higher than that of ALL-2005 regimen, it is more suitable for the ALL patients with BCR-ABL


Subject(s)
Adolescent , Aged , Antineoplastic Combined Chemotherapy Protocols , Child , Disease-Free Survival , Humans , Male , Neoplasm Recurrence, Local , Patients , Prognosis , Retrospective Studies , Treatment Outcome
5.
Chinese Journal of Radiology ; (12): E010-E010, 2020.
Article in Chinese | WPRIM | ID: wpr-811619

ABSTRACT

Objective@#To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou.@*Methods@#A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People’s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed.@*Results@#The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung.@*Conclusions@#The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.

6.
Journal of Experimental Hematology ; (6): 1381-1385, 2020.
Article in Chinese | WPRIM | ID: wpr-827108

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and prognostic risk factors of HLH children with central nervous system (CNS) involvement so as to provide more reference for further improving the prognosis of HLH children.@*METHODS@#The clinical data of 45 HLH children with CNS involvement treated in our hospital from January 2006 to October 2016 were collected and analyzed retrospectively. The clinical characteristics of HLH children with CNS involvement were recorded, moreover the possible factors influencing the prognosis of HLH children with CNS involvement were analyzed using univariate and multivariate analysis through the establishment of Cox risk ratio model.@*RESULTS@#Among 45 HLH children with CNS involvement, male was 19 cases and female was 26 cases. The median age of 4.0 years old (1.0-15.1). The detection showed that EBV found in 38 cases (84.44%), CMV infection in 1 case (2.22%), bacterial infection in 3 cases (6.67%), connection tissue disease in 1 case (2.22%) and indefinite etiology infection in 2 cases (4.44%). After lumbar puncture of 27 HLH children with CNS involvement, 10 cases (37.04%) showed cerebrospinal fluid abnormality. In addition, 22 cases showed the craniography abnormality. The follow-up results showed that the OS rate of 1 year was 46.67% (21/45), the OS rate of 3 years was 44.44% (20/45); the median survival time was 5.0 months. The OS analysis indicated that 1 years OS rate of diseased children with cerebrospinal fluid abnormality was significantly lower than that of diseased children with cerebrospinal fluid normality (10/45 vs 17/45) (P<0.05), and 1 years OS rate of diseased children who not received intrathecal injection was significantly lower that of diseased children who received intrathecal (10/45 vs 17/45) (P<0.05). The univariate analysis showed that the symptoms of nervous system, abnormal cerebrospinal fluid, absence of intrathecal injection and treatment schedule all were the risk factors affecting the prognosis of HLH children with CNS involvement (P<0.05). The multivariate analysis by Cox risk model showed that abnormal cerebrospinal fluid and absence of intrathecal injection were independent risk factors for of HLH children with CNS involvement (P<0.05).@*CONCLUSION@#The clinical prognosis of HLH children with CNS involvement is relatively poor, moreover some of HLH children with CNS involvement have neural sequelae. The cerebrospinal fluid abnormality and absence of intrathecal injection are independent risk factors leading to poor prognosis for HLH clildren with CNS involvement.


Subject(s)
Child , Child, Preschool , Cytomegalovirus Infections , Female , Humans , Male , Nervous System , Prognosis , Retrospective Studies , Risk Factors
7.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-827016

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
8.
Chinese Journal of Radiology ; (12): 010-010, 2020.
Article in Chinese | WPRIM | ID: wpr-787572

ABSTRACT

Objective@#To investigate the initial HRCT manifestations and clinical features of imported novel coronavirus pneumonia (NCP) in Guangzhou.@*Methods@#A retrospective analysis of 91 NCP patients admitted to the Guangzhou Eighth People’s Hospital from January 22 to 30, 2020 was performed including 39 males and 52 females, with a median age of 50 (33-62) years, then their clinical features and HRCT characteristics were analyzed.@*Results@#The main clinical presentations included fever in 70 cases and cough in 57 cases(mainly dry coughin39 cases). The first time HRCT showed that 24 cases with NCP were normal, however other 67 cases were abnormal. The ground glass opacity in the lung on HRCT was found in 65 cases, including 64 cases with dilated blood vessel crossing the lesion, 50 cases with thickened adjacent pleura, and 47 cases with thickening of interstitial septum. The patchy opacity was seen in 42 cases, and no enlarged lymph nodes were observed in all patients. As for the lesion distribution, there were two cases with bilateral diffuse changes, 57 cases with multiple lesions, 8 cases with the lesion in only one lobe. The lesions were mainly located under the pleura area in 46 cases, including 39 cases in the lower lobe and other 7 cases in the upper lobe. And there were 13 cases without characteristic distribution in the lung.@*Conclusions@#The initial images of NCP in Guangzhou mainly showed multiple ground glass opacity, which were mostly seen in the subpleural and lower lung fields, most of them with thickened pulmonary interstitium. Guangzhou has a higher proportion of NCP patients with mild and general patients, and some confirmed patients show negative HRCT for the first time. Patients without HRCT changes should be reviewed in a timely manner.

9.
Acta Pharmaceutica Sinica B ; (6): 1073-1082, 2020.
Article in English | WPRIM | ID: wpr-828823

ABSTRACT

Twelve new grayanoids (-) along with five known compounds were isolated from flowers of . Their structures were fully characterized using a combination of spectroscopic analyses, computational calculations, and single crystal X-ray diffraction. Rhomollone A () possesses an unprecedented 5/6/6/5 tetra-cyclic ring system (B- grayanane) incorporating a cyclopentene-1,3-dione scaffold. Rhodomollein XLIII () is a dimeric grayanoid, containing a novel 14-membered heterocyclic ring with a symmetry axis. The antinociceptive activities of compounds , , , , and - were evaluated by an acetic acid-induced writhing test. Among them, compounds , , , and displayed significant antinociceptive activities at a dose of 20 mg/kg with inhibition rates ranging from 41.9% to 91.6%. Compounds and inhibited 46.0% and 39.4% of the acetic acid-induced writhes at a dose of 2 mg/kg, while compound inhibited 34.3% of the writhes at a dose of 0.4 mg/kg.

10.
Protein & Cell ; (12): 483-504, 2020.
Article in English | WPRIM | ID: wpr-828752

ABSTRACT

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

11.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828746

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
12.
Protein & Cell ; (12): 483-504, 2020.
Article in English | WPRIM | ID: wpr-828588

ABSTRACT

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

13.
Protein & Cell ; (12): 740-770, 2020.
Article in English | WPRIM | ID: wpr-828582

ABSTRACT

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.


Subject(s)
Adult , Aged , Aged, 80 and over , Aging , Genetics , Allergy and Immunology , Betacoronavirus , CD4-Positive T-Lymphocytes , Metabolism , Cell Lineage , Chromatin Assembly and Disassembly , Coronavirus Infections , Allergy and Immunology , Cytokine Release Syndrome , Allergy and Immunology , Cytokines , Genetics , Disease Susceptibility , Flow Cytometry , Methods , Gene Expression Profiling , Gene Expression Regulation, Developmental , Gene Rearrangement , Humans , Immune System , Cell Biology , Allergy and Immunology , Immunocompetence , Genetics , Inflammation , Genetics , Allergy and Immunology , Mass Spectrometry , Methods , Middle Aged , Pandemics , Pneumonia, Viral , Allergy and Immunology , Sequence Analysis, RNA , Single-Cell Analysis , Transcriptome , Young Adult
14.
Article in Chinese | WPRIM | ID: wpr-828161

ABSTRACT

This study aimed to explore the role of miR-130a-3p in cardiomyocyte hypertrophy and its underlying mechanisms. Pressure-overload induced myocardial hypertrophy mice model was constructed by thoracic aortic constriction (TAC). , norepinephrine (NE) was used to stimulate neonatal rat cardiomyocytes (NRCMs) and H9c2 rat cardiomyocytes to induce hypertrophic phenotypes. The expression of miR-130a-3p was detected in mice hypertrophic myocardium, hypertrophic NRCMs and H9c2 cells. The mimics and inhibitors of miR-130a-3p were transfected into H9c2 cells to observe the role of miR-130a-3p on the hypertrophic phenotype change of cardiomyocytes separately. Furthermore, whether miR-130a-3p regulated hypertrophic related signaling pathways was explored. The results showed that the expression of miR-130a-3p was significantly decreased in hypertrophic myocardium, hypertrophic NRCMs and H9c2 cells. After transfection of miR-130a-3p mimics, the expression of hypertrophic marker genes, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and β-myosin heavy chain (β-MHC), and the cell surface area were notably down-regulated compared with the control group (mimics N.C. + NE group). But after transfection of miR-130a-3p inhibitor, the expression of ANP, BNP and β-MHC in H9c2 cells increased significantly, and the cell area increased further. By Western blot, it was found that the protein phosphorylation level of Akt and mTOR were down-regulated after over-expression of miR-130a-3p. These results suggest that miR-130a-3p mimics may alleviate the degree of cardiomyocyte hypertrophy, meanwhile its inhibitor can further aggravate cardiomyocyte hypertrophy. Over-expression of miR-130a-3p may attenuate cardiomyocytes hypertrophy by affecting the Akt pathway.


Subject(s)
Animals , Atrial Natriuretic Factor , Cardiomegaly , Mice , MicroRNAs , Genetics , Myocardium , Pathology , Myocytes, Cardiac , Pathology , Myosin Heavy Chains , Natriuretic Peptide, Brain , Nonmuscle Myosin Type IIB , Proto-Oncogene Proteins c-akt , Rats
15.
Article in Chinese | WPRIM | ID: wpr-756509

ABSTRACT

A large amount of non-coding RNA are found existing in eukaryotic transcriptome, which play an important role in regulating the expression of genes as well as participating in physiological and pathological process of various cells.In recent years,the research of ncRNA in diagnosis of breast cancer is extremely hot. In this review, the research of three types of peripheral blood ncRNAs as breast cancer diagnostic biomarkers were reviewed, including microRNA(miRNA), long non-coding RNA(lncRNA), and circular RNA(circRNA).Also,the prospect of ncRNA in clinical research and translational medicine of breast cancer was mentioned, in order to provide a new idea for breast cancer with the discovery of diagnostic markers in early detection and the monitoring of diagnosis and treatment process.

16.
Journal of Experimental Hematology ; (6): 1767-1773, 2019.
Article in Chinese | WPRIM | ID: wpr-781399

ABSTRACT

OBJECTIVE@#To analyze the related factors affecting the long-term prognosis of acute myeloid leukemia (AML) children with positive RUNX1-RUNX1T1.@*METHODS@#The clinical data of 63 chlidren with positive RUNX1-RUNX1T1 AML treated by BCH-AML 05 regimen in our hospital from January 2010 to December 2015 were collected and analyzed retrospectively. The level of RUNX1-RUNX1T1 was detected at the time of initial diagnosis (T), after the first induction treatment (T), after the second induction treatment (T), after the first consolidation treatment (T), after the second consolidation treatment (T) and after the third consolidation treatment (T). According to the fusion transcript levels of RUNX1-RUNX1T1 the AML children were divided into low-expression group and high-expression group; the threshold values for grouping were 10 copies/10 β-glucuronidase (GUS), 10 copies/10 GUS, 10 copies/10 GUS, 10 copies/10 GUS, 1 copies/10 GUS and 0 copies respectively. The gained data were enrolled in the statistical analysis.@*RESULTS@#23 cases of 63 children died during the follow-up period, and the median follow-up time of the remaining 40 children were 30.04 (11-60) months. There were statistically significant differences in CD15 positive rate between low-expression group and high-expression group (P0.05). Univariate analysis showed that sex, Plt counts at T and fusion transcript levels at T, T and T correlated with the 5-year overall survival rate (P10 copies/10 GUS at T was an independent risk factor for 5-year overall survival rate (HR=2.13, 95%CI: 1.04-7.78)(P<0.05).@*CONCLUSION@#The fusion transcript level after the first induction therapy in RUNX1-RUNX1T1-positive AML children is an independent factor influencing the long-term prognosis.


Subject(s)
Child , Core Binding Factor Alpha 2 Subunit , Humans , Leukemia, Myeloid, Acute , Oncogene Proteins, Fusion , Prognosis , RUNX1 Translocation Partner 1 Protein , Retrospective Studies
17.
Protein & Cell ; (12): 417-435, 2019.
Article in English | WPRIM | ID: wpr-757930

ABSTRACT

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

18.
Protein & Cell ; (12): 249-271, 2019.
Article in English | WPRIM | ID: wpr-757893

ABSTRACT

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes, including activation of the NOTCH and NF-κB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient's iPSCs. Importantly, the abnormal upregulation of NF-κB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSC-based disease model, our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease.

19.
Protein & Cell ; (12): 649-667, 2019.
Article in English | WPRIM | ID: wpr-757890

ABSTRACT

RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclear. Here we generated RAP1-deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells. Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.

20.
Article in Chinese | WPRIM | ID: wpr-801271

ABSTRACT

Objective@#To describe the influence of post-operative anatomical structure changes on nasal airflow characteristics by 3D reconstruction and numerical simulation in real cases after nasalisation with Draf Ⅲ so as to explore the correlation between the changes of anatomical structure and subjective symptoms as well as airflow characteristics.@*Methods@#Ten patients underwent nasalization with Draf Ⅲ in Department of Rhinology in Beijing Tongren Hospital from 2006 to 2018 were selected retrospectively. Postoperative follow-up of all patients was more than 1 year. All patients had no abnormalities in their paranasal sinus CT scans and Lund-Kennedy scores were 0 except scar. VAS scores including nasal obstruction, stimulation in frontal sinus, and headache were collected at the same period. The control model was a normal person. Numerical simulation was used for calculating airflow characteristics in deep inspiratory period of both models. Independent sample Mann-Whitney U test and Spearman correlation test were used by software SPSS 22.0.@*Results@#The airflow pressure in frontal sinus ostium was (7.21±1.39)×104 Pa (Mean±SD), which was lower than that in normal subjects (8.99×104 Pa) under deep inspiratory simulation. But, the velocities in frontal sinus ostium and frontal sinus were (40.10±2.46) m/s and (28.19±1.73) m/s respectively, which were higher than those in normal one (2.70 m/s, 0.73 m/s). The airflow patterns of the two models were basically similar. There was no significant difference in the opening size and volume of frontal sinus between different groups after grouped by three symptoms respectively. No correlation could be found between the opening size and volume of the frontal sinus with the appearance and severity of three subjective symptoms.@*Conclusions@#The airflow pattern and distribution after nasalisation with Draf Ⅲ are like those of normal person. There is no correlation between the changes of anatomy in frontal recess and frontal sinus and nasal airflow characteristics as well as subjective symptoms.

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