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1.
J Alzheimers Dis ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35491795

RESUMO

BACKGROUND: The established causative mutations in the APP, PSEN1, and PSEN2 can explain less than 1%,Alzheimer's disease (AD) patients. Of the identified variants, the PSEN2 mutations are even less common. OBJECTIVE: With the genetic study from the dementia cohort of Peking Union Medical College Hospital (PUMCH), we aim to illustrate the PSEN2 mutation spectrum and novel functionally validated mutations in Chinese AD patients. METHODS: 702 AD participants, aged 30-85, were identified in PUMCH dementia cohort. They all received history inquiry, physical examination, biochemical test, cognitive evaluation, brain CT/MRI, and next-generation DNA sequencing. Functional analysis was achieved by transfection of the HEK293 cells with plasmids harboring the wild-type PSEN2 or candidate mutations. RESULTS: Nine PSEN2 rare variants were found, including two reported (M239T, R62C) and seven novel variants (N141S, I368F, L396I, G117X, I146T, S147N, H220Y). The HEK293 cells transfected with the PSEN2 N141S, M239T, I368F plasmids showed higher Aß 42 and Aß 42/Aß 40 levels relative to the wild-type PSEN2. The PSEN2 L396I, G117X, S147N, H220Y, and R62C did not alter Aß 42, Aß 40 levels, or Aß 42/Aß 40 ratio. 1.9%,(13/702) subjects harbored rare PSEN2 variants. 0.4%,(3/702) subjects carried pathogenic/likely pathogenic PSEN2 mutations. The three subjects with the functionally validated PSEN2 mutations were all familial early-onset AD patients. The common symptoms included amnesia and mental symptom. Additionally, the M239T mutation carrier presented with dressing apraxia, visuospatial agraphia, dyscalculia and visual mislocalization. CONCLUSION: The PSEN2 N141S, M239T, and I368F are functionally validated mutations.

2.
Neurol Sci ; 43(5): 3255-3263, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34997422

RESUMO

OBJECTIVE: The objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD. METHODS: Forty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed. RESULTS: The patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular "butterfly wings" like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found. CONCLUSIONS: We emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.


Assuntos
Adrenoleucodistrofia , Adolescente , Adrenoleucodistrofia/diagnóstico por imagem , Adrenoleucodistrofia/genética , Animais , Criança , China , Feminino , Genótipo , Humanos , Neuroimagem , Fenótipo
3.
J Pers Med ; 12(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35055352

RESUMO

Background: Mini-Mental State Examination (MMSE) is the most widely used tool in cognitive screening. Some individuals with normal MMSE scores have extensive cognitive impairment. Systematic neuropsychological assessment should be performed in these patients. This study aimed to optimize the systematic neuropsychological test battery (NTB) by machine learning and develop new classification models for distinguishing mild cognitive impairment (MCI) and dementia among individuals with MMSE ≥ 26. Methods: 375 participants with MMSE ≥ 26 were assigned a diagnosis of cognitively unimpaired (CU) (n = 67), MCI (n = 174), or dementia (n = 134). We compared the performance of five machine learning algorithms, including logistic regression, decision tree, SVM, XGBoost, and random forest (RF), in identifying MCI and dementia. Results: RF performed best in identifying MCI and dementia. Six neuropsychological subtests with high-importance features were selected to form a simplified NTB, and the test time was cut in half. The AUC of the RF model was 0.89 for distinguishing MCI from CU, and 0.84 for distinguishing dementia from nondementia. Conclusions: This simplified cognitive assessment model can be useful for the diagnosis of MCI and dementia in patients with normal MMSE. It not only optimizes the content of cognitive evaluation, but also improves diagnosis and reduces missed diagnosis.

4.
J Alzheimers Dis ; 85(4): 1511-1518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34958020

RESUMO

BACKGROUND: The previous studies have identified several genes in relation to Alzheimer's disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions. OBJECTIVE: To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients. METHODS: 75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aß42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis. RESULTS: The rs7412-CC (APOE) genotype showed lower CSF Aß42 level and higher p-tau/Aß42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aß42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aß42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype. CONCLUSION: Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aß42, p-tau. or p-tau/Aß42.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Doença de Alzheimer/genética , Secretases da Proteína Precursora do Amiloide/genética , Apolipoproteínas E/genética , Ácido Aspártico Endopeptidases/genética , Biomarcadores/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Alelos , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , alfa-Macroglobulinas/genética
5.
Clin Neurol Neurosurg ; 210: 107012, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34749022

RESUMO

OBJECTIVE: Our study aimed to identify the appropriate evaluation time point and assessment forthe CSF tap test(TT) to predict the shunting responsiveness of patients with idiopathic normal-pressure hydrocephalus (iNPH). METHODS: Eighty-eight inpatients with clinically possible iNPH who underwent CSF TT at multiple time points (baseline, 8 hours, 24 hours, and 72 hours after CSF TT) at Peking Union Medical College Hospital were recruited. The multidomain assessment included the timed up and go test(TUG), 10-meter walking tests, and a brief executive function battery. Performance in multidomain assessment at the indicated time points were compared. The positive response rate and cumulative positive rate of multidomain assessment at multiple time points were calculated. And their corresponding specificity and sensitivity of predicting shunting response were calculated according to the follow-up results after shunting. RESULTS: The multidomain assessment performance except TUG at 8 hours were significantly improved at each time point after CSF TT compared with baseline (P<0.01). Reduction more than 10% in the 10-meter walking time and number of steps at 24 hours showed the highest specificity (both 85.7%) and sensitivity (37.5% and 46.7%, respectively) for predicting shunting response. Additionally, an improvement of more than 20% in the composite z score at 72 hours showed 100% specificity and 80% sensitivity for predicting shunting response. CONCLUSION: Multiple time points and multidomain assessment were helpful to identify more shunting responders. Executive function evaluation might be a candidate tool to increase the effectiveness of CSF TT.


Assuntos
Derivações do Líquido Cefalorraquidiano/métodos , Hidrocefalia de Pressão Normal/líquido cefalorraquidiano , Hidrocefalia de Pressão Normal/cirurgia , Testes de Estado Mental e Demência , Punção Espinal/métodos , Teste de Caminhada/métodos , Idoso , Função Executiva/fisiologia , Feminino , Seguimentos , Humanos , Hidrocefalia de Pressão Normal/diagnóstico , Hidrocefalia de Pressão Normal/psicologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo
6.
Ying Yong Sheng Tai Xue Bao ; 32(9): 3167-3176, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34658202

RESUMO

Niche shift between polyploid and diploid plants is an important requirement for the success of polyploid. Diploid, tetraploid, and hexaploid of kiwifruit distribute in different areas. Whether there is obvious niche differentiation and the major environmental factors which could influence the ecological niche of different ploidy kiwifruits are still unknown. Based on the natural distribution information collected from literature and by field works, the maximum entropy model (MaxEnt) was used to predict the potentially suitable ranges and the major climatic factors affecting distribution of different ploidy kiwifruits. Niche divergence between different ploidy kiwifruits was quantified by niche identity test. The results showed that there were obvious differences in the potential suitable areas of different ploidy kiwifruits. Diploid occurred in lower altitude Hunan foothills. Tetraploid nearly overlapped with diploid but tended to northern Guizhou and eastern Chongqing. Hexaploid were centered in Guizhou Plateau, northwestern Hunan, southwestern Hubei and southern Shanxi. Hexaploid kiwifruits preferred higher altitudes and latitudes. In addition, the hexaploid had wider highly suitable areas. Results of niche identity test showed overlapped niches between diploid and tetraploid, and different niches between diploid/tetraploid and hexaploid kiwifruits. Minimum temperature of the coldest month (Bio6) and precipitation of the driest month (Bio14) were key environmental factors driving the niche shift of ploidy kiwifruits. Polyploid kiwifruits could maintain a higher probability of existence under lower Bio6 and Bio14, which indicated more extreme niche in cold and arid mountains for polyploids.


Assuntos
Actinidia , Diploide , Actinidia/genética , Ecossistema , Plantas , Poliploidia
7.
Brain Behav ; 11(11): e2373, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34555265

RESUMO

INTRODUCTION: To investigate the heterogeneous effect of Apolipoprotein E (ApoE) genotype on clinical phenotypes in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD), respectively. METHODS: 785 probable AD patients were enrolled from the dementia cohort of Peking Union Medical College Hospital (PUMCH), China. There were 386 EOAD and 399 LOAD cases. All individuals finished history inquiry, neurological examination, blood biochemical test, neuropsychological screening test, electroencephalography, brain CT/MRI, and ApoE genotyping. Some participants had neuropsychological domain assessment (n = 317), MRI morphometry (n = 130), CSF testing of Aß42, p-tau, t-tau (n = 144), or DNA sequencing (n = 690). The variables were compared mainly between ɛ4 carriers and non-carriers in EOAD and LOAD, respectively. RESULTS: In LOAD, ɛ4 carriers showed female predominance; worse performance in trail making test, delayed recall of auditory verbal learning test (AVLT) and rey complex figure; smaller hippocampal, parahippocampal, and entorhinal volume, as compared to ɛ4 non-carriers. In EOAD, ɛ4 carriers had lower scores in AVLT, episodic memory and modified Luria's tapping task; but less cortical atrophy in entorhinal, middle cingulate, inferior frontal, and parieto-occipital regions, in comparison to ɛ4 non-carriers. 6.2% (43/690) subjects harbored potential causative mutations in APP, PSEN1, and PSEN2. In both EOAD and LOAD, no differences were observed between ɛ4 carriers and non-carriers in CSF levels of Aß42, p-tau, t-tau, or mutation frequency. CONCLUSIONS: ApoE exerts a heterogeneous effect on clinical phenotypes in EOAD and LOAD, which might be related to the different genetic and pathological basis underlying them.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Apolipoproteínas E/genética , Feminino , Genótipo , Hospitais , Humanos , Fenótipo
8.
Bioresour Technol ; 337: 125456, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34320740

RESUMO

Microbial pretreatment to lignocellulosic biomass for anaerobic digestion (AD) has achieved increased attention; however, the low efficiency and unclear mechanism of oxygen parameter affecting this process performance limit its practical application. In this study, five readily available microbial consortia were developed to analyze the influences of various oxygen concentrations during pretreatment process upon methane conversion efficiency and microbiota within AD of giant grass. Results found that anaerobic pretreatment by liquid or straw composting inoculant, along with microaerobic pretreatment by cow manure at 10 mL/g VS oxygen concentration, obtained 23.1%, 24.4%, and 16.0% higher methane yields (275.3, 279.8, and 265.3 mL/g VS) than corresponding untreated group, respectively. Microbial community analyses showed that microbial responses to oxygen varied significantly with microbial consortium, which consequently caused different AD performances. The findings will enrich theoretical knowledge of microbial pretreatment and provide a technological guidance for efficient utilization of giant grass and other lignocellulosic biomasses.


Assuntos
Biocombustíveis , Poaceae , Anaerobiose , Animais , Bovinos , Feminino , Esterco , Metano
9.
Curr Alzheimer Res ; 18(3): 265-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34102969

RESUMO

BACKGROUND: Alzheimer's disease with a causative genetic mutation (AD-CGM) is an uncommon form, characterized by a heterogeneous clinical phenotype and variations in the genotype of racial groups affected. OBJECTIVE: We aimed to systemically describe the phenotype variance and mutation spectrum in the large sample size of the Peking Union Medical College Hospital (PUMCH) cohort, Beijing, China. METHODS: Next-generation sequencing (NGS) was carried out in 1108 patients diagnosed with dementia. A total of 40 Han Chinese patients with three AD gene mutations were enrolled. A systemic review of all the patients was performed, including clinical history, neurocognitive assessment, brain magnetic resonance imaging, and cerebrospinal fluid (CSF) biomarkers. RESULTS: We studied the following gene mutation variants: 12 AßPP, 13 PSEN1, and 9 PSEN2, and 23 among them were novel. Most of them were early-onset, but PSEN1 mutation carriers had the youngest onset age. The commonest symptoms were similar to those of AD, including an amnestic syndrome, followed by psychiatric symptoms and movement disorder. On MRI, parietal and posterior temporal atrophy was prominent in PSEN1 and PSEN2 mutation carriers, while AßPP mutation carriers had more vascular changes. The CSF biomarkers profile was indistinguishable from sporadic AD. CONCLUSION: We identified a small group of AD-CGM subjects representing 3.6% among more than 1000 demented patients in the PUMCH cohort. These subjects usually presented with early-onset dementia and exhibited significant clinical and genetic heterogeneity. Identification required complete screening of genetic mutations using NGS. Although family history was usually present, we found non-familial cases of all three genetic mutations.


Assuntos
Doença de Alzheimer/genética , Mutação/genética , Fenótipo , Adulto , Precursor de Proteína beta-Amiloide/genética , China , Estudos de Coortes , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Presenilina-1/genética , Presenilina-2/genética
10.
J Alzheimers Dis ; 82(1): 205-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34024840

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are widely accepted as manifestations of Alzheimer's disease (AD) pathogenesis and incorporated into biological definition of AD. However, the correlations between CSF and other biomarkers such as neuroimaging and neuropsychiatric evaluation are complicated and inconsistent. OBJECTIVE: We aimed to better interpreting CSF biomarkers results accompanying with other indexes in improving accurate diagnosis of AD. METHODS: 112 AD patients and 30 cognitive normal controls were selected. Commercial accessible ELISA kits were introduced for measurement of CSF t-tau, p-tau181, Aß1-42, and NfL based on standard protocol. MRI examinations were performed using a 3-T MRI scanner and visual rating scales including medial temporal atrophy score and Koedam's scale were used to evaluate medial temporal atrophy and posterior region atrophy. RESULTS: CSF biomarkers' profile including decreased concentration of Aß1-42, increased concentration of t-tau, p-tau181, t-tau/Aß 1-42, and NfL were diagnostic between AD and control. CSF biomarkers profile was not influenced by the APOE genotype. Increased concentration of t-tau and NfL, as well as ratio of t-tau/Aß 1-42 were related to decrease of Mini-Mental State Examination (MMSE) score while concentration of Aß1-42 not. Visual assessed cortical atrophy was related to MMSE score, but most of the CSF biomarkers were not related to atrophy, except that increased concentration of p-tau181 was significantly associated with atrophy of posterior cortical region. CONCLUSION: Our results supported CSF biomarkers were helpful in diagnosis of AD. However, CSF biomarkers were cross-sectional reflection of pathogenesis, which did not correlate well with clinical progression. CSF biomarkers should be interpreted in combination with MRI and cognitive evaluation in clinical use.


Assuntos
Doença de Alzheimer/diagnóstico , Atrofia/patologia , Biomarcadores/líquido cefalorraquidiano , Cognição/fisiologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , China , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas tau/líquido cefalorraquidiano
11.
Clin Neurol Neurosurg ; 205: 106604, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33887505

RESUMO

INTRODUCTION: Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are the leading causes of dementia. To better understand the disease development of cognitive function and anatomical structure in AD and FTLD, we analyzed the changes in brain volume by MRI and the psychological test results. Here, we report a dynamic observation of brain structure. METHODS: Thirteen patients diagnosed with probable AD by the 2011 NIA-AA criteria and eight FTLD patients diagnosed by the FTLD criteria underwent MRI at baseline. All subjects were rescanned after 5 months to 3 years of follow-up. The anatomic changes on T1-weighted imaging of each subject were measured, and the separate changes in the two groups and the differences in the changes between AD and FTLD were analyzed. RESULTS: In AD patients, the anterior and posterior horns of the lateral ventricle and lateral fissure enlarged progressively (p < 0.001). The volume of the regions, including the medial and lateral temporal lobe, especially the parahippocampal gyrus, and the frontal lobe decreased significantly as the disease progressed (p < 0.001). Additionally, the volume of white matter in the frontal, parietal, temporal lobe and cerebellum decreased in a relatively symmetric pattern (p < 0.001). In FTLD patients, the anterior horn of the lateral ventricle, lateral fissure, cerebral longitudinal fissure, external space of the orbitofrontal cortex, and mesencephalon surrounding the cisterna were enlarged (p < 0.005), while regions including the left frontal lobe, anterior cingulate cortex, basal ganglia (especially the left basal ganglia), left lateral temporal lobe and inferior cerebellar vermis decreased as the disease progressed (p < 0.005). Regarding the differences between AD and FTLD, atrophy of the frontal lobe and bilateral basal ganglia was more significant in FTLD than in AD (p < 0.01). In addition, enlargements of the anterior horn of the lateral ventricle, left lateral fissure and interpeduncular cistern were more significant in FTLD patients than in AD patients (p < 0.01). CONCLUSIONS: These findings suggest that AD and FTLD have distinctly different atrophy patterns: AD patients show diffuse atrophy while FTLD patients show an asymmetrical focal atrophy pattern, which might explain the relatively better and longer preservation of daily living function in FTLD patients.

12.
Clin Neurol Neurosurg ; 203: 106552, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33601235

RESUMO

OBJECTIVE: White matter hyperintensities could be found in many degenerative dementias including Alzheimer's disease (AD). Pathogenesis of white matter hyperintensities in AD is complicated. We aim to identify the features of white matter hyperintensities and the atrophy pattern in early onset Alzheimer's disease with causative gene mutations. METHODS: 7 AD dementia patients with causative mutations were included and the clinical history, neuropsychology, neuroimaging,APOE genotype and whole-genome sequencing (WGS) were analyzed. Axial T1-weighted images and Fluid attenuated inversion recovery (FLAIR) were analyzed with visual rating scale to examine cortical atrophy and white matter hyperintensities. RESULTS: 5 female and 2 male patients with 4PSEN1, 2PSEN2 and 1APP mutation were included. The average age of onset was 46.7y/o (44-52) and the duration of disease was 28.6 months (8-60). Clinical phenotype included memory loss (100 %), visual/spatial disorder (100 %), executive dysfunction (100 %), calculation disorder (85.7 %), disorientation (85.7 %), language problem (57.1 %), personality change (28.6 %) and movement disorder (14.3 %). The grading of posterior cortex atrophy was higher than medial temporal lobe atrophy. Periventricular hyperintensities surrounding occipital and frontal horn of ventricle and sub-ventricular bands were most common, while small foci of lesions were also detected in deep white matter, sub-cortical and juxta-cortical area. Mutations carriers in the APP gene or PSEN1 gene postcodon 200 had more severe white matter hyperintensities than other mutations. CONCLUSION: White matter hyperintensities were found in early onset AD with causative mutations. The severity was related to genotypes and spatial distributions. Axon degeneration following neuronal loss and ischemic injury might be the pathogenesis of white matter damage. Severer atrophy in the posterior cortex than medial temporal lobe can present in early onset AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Mutação/genética , Substância Branca/patologia , Adulto , Idade de Início , Precursor de Proteína beta-Amiloide/genética , Atrofia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Presenilina-1/genética , Presenilina-2/genética
13.
J Mol Neurosci ; 71(5): 1015-1022, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33006106

RESUMO

Frontotemporal dementia (FTD) is a heterogeneous disease both clinically and pathologically. Genetic mutation in microtubule-associated protein tau (MAPT) is the most common cause of FTD, and the phenotype is related to the mutation location. However, the phenotype and genotype correlation varies somewhat among different cohorts and ethnicities. Whole-genome next-generation sequencing (NGS) was carried out for 1351 patients with dementia at Peking Union Medical College Hospital. MAPT variations classified as pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected, and the phenotype-genotype correlation was analyzed with a concurrent literature review. Twenty-four patients were enrolled; 8 patients carrying the D177V mutation are discussed separately. The average onset age was young, and most of them had a positive family history. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Most structural MRIs showed asymmetrical atrophy of the temporal lobe, with/without similar changes in the frontal lobe. L266V carriers presented with youngest onset typical behavior variant FTD or aphasia; P301L carriers presented with behavior variant FTD or aphasia. Functional MRI and molecular imaging also showed that the involved areas were similar to those with structural atrophy. D296N carriers presented atypical parkinsonism and cognitive dysfunction at older ages. Eight D177V carriers had extraordinarily different manifestations. The clinical phenotype of most of them was not FTD, though cerebral vascular lesions were obvious in some of them. MAPT mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps. The D177V mutation is possibly not directly pathogenic in our cohort. Some of the variants might increase the genetic risk of neurodegenerative diseases.


Assuntos
Demência Frontotemporal/genética , Mutação de Sentido Incorreto , Fenótipo , Proteínas tau/genética , Adulto , Idoso , Feminino , Demência Frontotemporal/patologia , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade
14.
Biomed Pharmacother ; 133: 111044, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378952

RESUMO

Traditional Chinese Medicine (TCM) has the characteristics of multiple targets, slight side effects and good therapeutic effects. Good anti-tumor effects are shown by Traditional Chinese Medicine prescription, Chinese patent medicine, single Traditional Chinese Medicine and Traditional Chinese medicine monomer compound. Clinically, TCM prolonged the survival time of patients and improved the life quality of patients, due to less side effects. Cancer metastasis is a complex process involving numerous steps, multiple genes and their products. During the process of tumor metastasis, firstly, cancer cell increases its proliferative capacity by reducing autophagy and apoptosis, and then the cancer cell capacity is stimulated by increasing the ability of tumors to absorb nutrients from the outside through angiogenesis. Both of the two steps can increase tumor migration and invasion. Finally, the purpose of tumor metastasis is achieved. By inhibiting autophagy and apoptosis of tumor cells, angiogenesis and EMT outside the tumor can inhibit the invasion and migration of cancer, and consequently achieve the purpose of inhibiting tumor metastasis. This review explores the research achievements of Traditional Chinese Medicine on breast cancer, lung cancer, hepatic carcinoma, colorectal cancer, gastric cancer and other cancer metastasis in the past five years, summarizes the development direction of TCM on cancer metastasis research in the past five years and makes a prospect for the future.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Medicina Tradicional Chinesa/efeitos adversos , Metástase Neoplásica , Neoplasias/metabolismo , Neoplasias/patologia , Resultado do Tratamento
15.
Cancer Manag Res ; 12: 10715-10723, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33149678

RESUMO

PURPOSE: To determine whether pelvic lymphadenectomy improved survival in patients diagnosed with low-risk early-stage endometrial cancer by intraoperative pathology. METHODS: This retrospective analysis included 238 patients at our hospital. RESULTS: The lymphadenectomy and non-lymphadenectomy groups contained 121 and 117 patients, respectively. In both groups, more than half the patients had tumor size ≥2 cm, and most had myometrial invasion <50%, stage Ia disease and no lymphovascular space invasion. Age, tumor size, myometrial invasion, surgical-pathologic stage and postoperative adjuvant therapy use were comparable between groups. The non-lymphadenectomy group had more patients treated laparoscopically (36.8% vs 10.7%; P<0.001) and fewer patients with histologic grade 2 disease (35.9% vs 62.8%; P<0.001) than the lymphadenectomy group. In the non-lymphadenectomy group, intraoperative frozen section pathology disagreed with postoperative pathology in only 31/117 cases for histologic grade (none upgraded to grade 3), 1/117 cases for myometrial invasion (one case revised from <50% to ≥50%) and 3/117 cases for surgical-pathologic stage (upgraded from Ia to Ib or II). Disease recurrence rate and overall survival did not differ significantly between the lymphadenectomy and non-lymphadenectomy groups. In multivariate Cox regression analysis, only surgical-pathologic stage >Ia (odds ratio, 47.7; 95% confidence interval, 6.7-340.8; P=0.031) was associated with increased odds of disease recurrence. CONCLUSION: Pelvic lymphadenectomy may not be necessary in patients with an intraoperative diagnosis of low-risk endometrial cancer.

16.
J Clin Neurosci ; 81: 105-110, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33222896

RESUMO

BACKGROUND: It is an economical strategy to design a screening method to decide which patients with amyotrophic lateral sclerosis/ motor neuron disease (ALS/MND) should enter into the stage for further comprehensive neuropsychological investigation. METHODS: 59 patients (including 8 with frank dementia) were recruited. They underwent the extensive neuropsychological evaluation and short screening batteries, namely the Mini-Mental State Examination (MMSE), the Peking Union Medical College Hospital version of Montreal Cognitive Assessment (MoCA-P) and the Frontal Assessment Battery (FAB). Results of the extensive neuropsychological evaluation were set as the gold standard to diagnose cognitive impairment, and the effectiveness of screening tests were measured against them. RESULTS: By comparing the sensitivity and specificity, we found that the combination of FAB plus both or either of the other 2 short batteries provided a satisfactorily high sensitivity, but none of these screening batteries was significantly associated with quantitative behavioral measurements among non-demented subjects, the Frontal Behavioral Inventory-ALS version (FBI-ALS). CONCLUSIONS: The combination of the FBI-ALS, the FAB, and the MMSE or the MoCA-P or both could effectively screen comorbid dementia, cognitive and behavioral impairment in ALS but this implicates a limited specificity. And the FAB needed to be validated in large Chinese sample.


Assuntos
Esclerose Amiotrófica Lateral/diagnóstico , Disfunção Cognitiva/diagnóstico , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Testes Neuropsicológicos , Sensibilidade e Especificidade
17.
Fitoterapia ; 147: 104763, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33080344

RESUMO

Two structurally unique polyphenols, alatains A (1) and B (2), were isolated from the bark of Cassia alata. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 represent a new type of hetero-dimeric polyphenols with a C-14-C-5' linkage, biogenetically formed by an unusual intermolecular oxidative phenol-coupling reaction between a chromone unit and an isocoumarin moiety. Moreover, compounds 1 and 2 showed significant anti-tobacco mosaic virus (anti-TMV) inhibition IC50 values of 18.8 and 11.4 µM, respectively. Alatains A and B also exhibited promising protective effects on TMV infection of the host plants (Nicotiana tabacum) with the inhibition rates of 54.6% and 69.7% at the concentration of 20 µM, respectively. The results provided a new structural template for potential anti-TMV agent discovery.


Assuntos
Antivirais/farmacologia , Cassia/química , Polifenóis/farmacologia , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Antivirais/isolamento & purificação , China , Cromonas , Isocumarinas , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Polifenóis/isolamento & purificação , Tabaco/virologia
18.
Oncol Lett ; 20(1): 685-692, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32565993

RESUMO

Ovarian cancer has a high incidence rate and mortality in gynaecologic malignancies. Epithelial ovarian cancer (EOC) accounts for >95% of ovarian cancer cases. Most of the patients with EOC are difficult to diagnose in early stage. The aim of the present study was to compare the long non-coding (lnc)RNA expression profiles of five ovarian cancer cell lines (IGROV1, A2780, SKOV3, ES2, and Hey) and an ovarian epithelial cell line (IOSE80) in order to identify differentially expressed lncRNAs and their associated microRNAs (miRNAs). The expression profiles of lncRNAs and mRNAs in these cell lines were determined by microarray gene analysis and reverse transcription-quantitative PCR. lncRNA neuropeptides B and W receptor 1-2 (NPBWR1-2) overexpression was induced in the SKOV3 cell line. Cell viability, proliferation, migration, invasion and apoptosis were evaluated using MTT, colony-formation, Transwell and flow cytometry assays, respectively. The microarray results indicated that several lncRNAs were differentially expressed in the five ovarian cancer cell lines compared with the normal ovarian epithelial cell line. Compared with IOSE80, lncRNA NPBWR1-2 was downregulated by more than two-fold in all five ovarian cancer cell lines. Moreover, NPBWR1-2 overexpression in the SKOV3 cell line decreased cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis compared with the control cells. A total of 20 miRNAs, which are involved in tumorigenesis and development, were predicted to be associated with NPBWR1-2 by bioinformatics analysis. The results of the present study suggest that lncRNA NPBWR1-2 affects the occurrence and development of ovarian cancer via multiple miRNAs, providing a theoretical basis for the development of novel clinical treatments.

19.
Gynecol Oncol ; 157(2): 536-541, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32173046

RESUMO

OBJECTIVE: To compare quality of life (Qol) of patients with stage IB2-IIA cervical cancer treated by neoadjuvant treatments followed by radical surgery (NTS) or standard chemoradiation (CRT). METHODS: Patients with stage IB2-IIA cervical cancer during 2006-2012 were treated with NTS or CRT and were invited to participate. The Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Questionnaire was used to assess patient Qol. A multivariable linear regression analysis was performed to identify factors associated with Qol. RESULTS: In total, 90 (78.3%) out of 115 eligible patients completed the questionnaires. No significant differences were found in Qol between treatment groups, except that patients after NTS reported higher scores in the social/family well-being (e.g. satisfaction with sexual life, close relationships with partner or friends, and support from friends) than those after CRT, in particular, during 2-3 years after treatment. Results of multivariate analysis indicated that NTS was associated with better social/family functioning, while advanced stage of cervical cancer, lower family income and lower education were associated with impaired Qol in different domains. CONCLUSIONS: Although self-reported Qol after treatment were not significantly different, NTS treated patients reported better social/family functioning than CRT treated patients, such as satisfaction with their sexual life and close relationships with partner or friends, during 2-3 years post treatment. These results were helpful for physicians to make treatment decisions while considering treatment-related Qol, and moreover, for rehabilitation and supportive care of patients after treatment. Further validation of our findings in randomized, controlled clinical trials is warranted.


Assuntos
Neoplasias do Colo do Útero/terapia , Quimiorradioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Qualidade de Vida , Estudos Retrospectivos , Fatores Socioeconômicos , Neoplasias do Colo do Útero/economia , Neoplasias do Colo do Útero/patologia
20.
Ann Transl Med ; 8(1): 7, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32055598

RESUMO

BACKGROUND: The genetic mechanisms of binge eating (BE) as a disease identity remain obscure. BE is usually viewed as a part of the behavioral variant of frontotemporal dementia (bvFTD) features. We encountered a family with hereditary diffuse leukoencephalopathy with spheroids (HDLS) that manifested uniformly with binge-eating-onset dementia. The genetic factors associated with the rare phenotype were investigated. METHODS: The detailed phenotypes of the patients were described. We performed whole-exome sequencing (WES) of family members and repeat-primed PCR to analyze the patients' expansion size of C9orf72, a well-established gene causing FTD. The WES results of additional HDLS patients without BE manifestations were also investigated. RESULTS: All affected individuals had a BE-dementia-epilepsy pattern of disease progression. A recurrent disease-causing mutation in CSF1R established the diagnosis of HDLS in the family. No abnormalities in the expansion size of C9orf72 were detected. The concurrence of a recurrent CSF1R mutation and a rare variant in NMUR2, a gene functionally related to BE, was revealed in the affected family members. No potentially pathogenic variants in other known BE-associated genes were identified. Both the NMUR2 variant and the CSF1R mutation cosegregated with the BE-dementia-epilepsy phenotype in the family. In three additional HDLS patients without BE, no pathogenic variants in NMUR2 were detected. CONCLUSIONS: We propose that synergistic genetic effects of NMUR2 and CSF1R variants may exist and contribute to the development of the BE phenotype in HDLS. NMUR2 is one of the potential susceptible genes in BE and may contribute in a background of a disrupted structural neuronetwork. Further studies in other BE-related disorders are required.

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