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1.
Ultrasound Med Biol ; 46(3): 610-619, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31810804

RESUMO

To assess the practicality of 3-D power Doppler angiography (3-D-CPA) for local drug perfusion dosage guidance of refractory infantile hemangioma (IH) treatment, 47 cases (48 lesions) of refractory IH were selected for local bleomycin infusion (once a month). Ultrasound was performed before treatment and 1 and 2 months after the first treatment. The 3-D volume (V) change of infantile hemangiomas and the ratio of bleomycin injection to 3-D V before treatment were calculated, and statistical analysis was performed. One month after percutaneous local drug perfusion, 37 participants (77.08%) exhibited significant improvement; controlled growth was observed on six lesions (12.5%); and treatment of the remaining 5 lesions (10.42%) failed to suppress growth. The calculated tolerable and effective dose of bleomycin for refractory IH was 0.34 ± 0.03 mL/cm3; the corresponding 3-D V decreased approximately 70.27 ± 6.27%. Three-dimensional CPA can provide abundant information on internal lesions. In particular, 3-D-CPA can quantitatively assess changes in lesion volume and guide the effective and rational use of interventional drugs.

2.
J Agric Food Chem ; 67(46): 12752-12760, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31642668

RESUMO

Atherosclerosis, the major risk of cardiovascular events, is a chronic vascular inflammatory disease. Pterostilbene is a naturally occurring dimethylated analogue of resveratrol and has recently been demonstrated to be beneficial against cardiovascular diseases. However, the underlying mechanisms of pterostilbene on atherosclerosis remain elusive. Experimental atherosclerosis was induced by a high-fat diet (HFD) in apolipoprotein E knockout (ApoE-/-) mice. Pterostilbene was administered intragastrically for 16 weeks. We found that pterostilbene significantly attenuated thoracic and abdominal atherosclerotic plaque formation in HFD-fed ApoE-/-mice, accompanied by modulated lipid profiles and reduced production of proinflammatory cytokines (including IL-6, IFN-γ, and TNF-α). In addition, pterostilbene restored vascular redox balance in thoracic and abdominal aorta, evidenced by enhanced catalase (CAT) expression and activities, and decreased malondialdehyde and H2O2 production. Notably, pterostilbene specifically induced CAT expression and activities in the vascular smooth muscle cells (VSMCs) of thoracic and abdominal aorta. In vitro, pterostilbene markedly promoted the expression and activity of CAT and decreased ox-low-density lipoprotein (LDL)-mediated VSMC proliferation and intracellular H2O2 production, which was abolished by CAT siRNA knockdown or inhibition. Pterostilbene-induced CAT expression was associated with inhibition of Akt, PRAS40, and GSK-3ß signaling activation and upregulation of PTEN. Our data clearly demonstrated that pterostilbene exerted an antiatherosclerotic effect by inducing CAT and modulating the VSMC function.


Assuntos
Aterosclerose/tratamento farmacológico , Catalase/metabolismo , Músculo Liso Vascular/enzimologia , Estilbenos/administração & dosagem , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo , Catalase/genética , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Interferon gama/genética , Interferon gama/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipoproteínas LDL/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/metabolismo , Oxirredução
3.
Chin Med J (Engl) ; 132(10): 1202-1207, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31140991

RESUMO

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy caused by multiple mtDNA abnormalities. There is little information about the changes of ocular fundus with CPEO. The aim of this work was to measure and evaluate changes in the macular retinal thickness and optic nerve head in patients with CPEO using spectral-domain optical coherence tomography and to compare the findings with those of healthy individuals. METHODS: Totally, 18 CPEO patients were enrolled in this study. Healthy volunteers matched for gender, age, and diopter settings were included as a control group. The retinal thickness of macular central fovea, inner and outer retinal layer thickness of perifoveal macular, optic nerve head parameters, and peripapillay retinal nerve fiber layer thickness (pRNFLT) for all included cases were measured using spectral-domain optical coherence tomography. A paired t test was used to compare the differences in the studied parameters between the two groups. The correlations between macular retinal thickness, pRNFLT, disease duration, and age of onset were also analyzed. RESULTS: Among the macular parameters, retinal thickness of macular central fovea (t = -2.135, P < 0.05) and outer retinal layer thickness (t = -1.994, P < 0.05) of patients in the CPEO group were statistically significant lower than those of patients in the normal control group. For the optic nerve head parameters, the patients in the CPEO group showed a larger rim volume (t = -2.499, P < 0.05) and nerve head volume (t = -2.103, P < 0.05). The overall pRNFLT of patients in the CPEO group was statistically significant lower than that of patients in the control group (t = -4.125, P < 0.05). The comparison of pRNFLT in eight sectors showed that the pRNFLT of patients in the CPEO group was statistically significant lower than that of the control group mainly in the inferior and temporal sectors. The degree of pRNFL defect negatively correlated with the disease duration (r = -0.583, P < 0.05). CONCLUSIONS: The retinal thickness of patients with CPEO was significantly thinner, which was mostly the outer retina. The patients' optic discs had a low volume and the loss of the retinal nerve fiber layer was obvious. With the extension of the disease duration, the retinal nerve fiber layer defect was even more significant.


Assuntos
Oftalmoplegia Externa Progressiva Crônica/diagnóstico , Tomografia de Coerência Óptica/métodos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Disco Óptico/patologia , Retina/patologia , Células Ganglionares da Retina/patologia , Adulto Jovem
4.
Curr Med Sci ; 39(1): 138-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868504

RESUMO

Quantitative magnetic resonance image (MRI) in individual muscles may be useful for monitoring disease progression in Duchenne muscular dystrophy (DMD). The purpose of this study was to measure T2 relaxation time of thigh muscles in children with DMD and healthy boys, and to correlate the T2 relaxation time of muscles with the fat fraction (FF) at quantitative magnetic resonance and results of clinical assessment. Thirty-two boys with DMD and 18 healthy boys were evaluated with T2 mapping and three-point Dixon MRI. Age, body mass index (BMI), muscle strength assessment, timed functional tests (time to walk or run 10 metres, rise from the floor and ascend four stairs), and the North Star Ambulatory Assessment (NSAA) were evaluated. Spearman's correlation was used to assess the relationships between FF and clinical assessments and T2 relaxation time. The mean T2 relaxation time of thigh muscles in DMD was significantly longer than that in the control group (P<0.05), except for the gracilis (P=0.952). The gracilis, sartorius and adductor longus were relatively spared by fatty infiltration in DMD patients. The T2 relaxation time was correlated significantly with the mean FF in all muscles. Age, BMI, total muscle strength score, timed functional tests and NSAA were significantly correlated with the overall mean T2 relaxation time. T2 mapping may prove clinically useful in monitoring muscle changes as a result of the disease process and in predicting the outcome of DMD patients.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Distrofia Muscular de Duchenne/diagnóstico por imagem , Coxa da Perna/diagnóstico por imagem , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Pré-Escolar , Progressão da Doença , Humanos , Imagem por Ressonância Magnética , Masculino , Estudos Prospectivos
5.
Chin Med J (Engl) ; 132(3): 269-274, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30681492

RESUMO

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ±â€Šstandard deviation, 2.79 ±â€Š1.47 vs. 3.83 ±â€Š1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS: The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.


Assuntos
Acidose Láctica/tratamento farmacológico , Acidose Láctica/mortalidade , Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Encefalomiopatias Mitocondriais/tratamento farmacológico , Encefalomiopatias Mitocondriais/mortalidade , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Adolescente , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lamotrigina/uso terapêutico , Levetiracetam/administração & dosagem , Masculino , Oxcarbazepina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Topiramato/uso terapêutico , Ácido Valproico/uso terapêutico
6.
Acta Biomater ; 80: 308-326, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30240955

RESUMO

Breast cancer is a severe threat to the health and lives of women due to its difficult early diagnosis and the unsatisfactory therapeutic efficacy of breast cancer treatments. The development of theranostic strategies to combat breast cancer with high accuracy and effectiveness is therefore urgently needed. In this study, we describe a near-infrared (NIR) light-controllable, targeted and biocompatible drug delivery nanoplatform (PFH-PTX@PLGA/SPIO-Her) for photoacoustic (PA)/ultrasound (US) bimodal imaging-guided photothermal (PTT)/chemo synergistic cancer therapy of breast cancer. Carboxyl-modified PEGylated poly (lactic-co-glycolic acid) (PLGA-PEG-COOH) constituted the skeleton of the nanoplatform. Especially, the antibody Herceptin was modified onto the surface of nanoplatform for active HER2-targing to facilitate the tumor accumulation of the nanoplatform. The encapsulated superparamagnetic iron oxide (SPIO) nanoparticles could be employed as an excellent PA imaging agent to guide tumor therapy. When exposed to NIR light, the SPIO also could transform NIR light into thermal energy for photothermal ablation of tumor. The NIR-induced thermal effect subsequently triggered the optical droplet vaporization (ODV) of perfluorohexane (PFH) to generate PFH gas bubbles, which not only achieved the US imaging enhancement, but also contributed to the release of loaded paclitaxel (PTX) from the nanoplatform for significantly improving PTT therapeutic efficacy. Our results demonstrated that the targeted tumor accumulation, accurate real-time bimodal imaging, and the abundant drug release at the tumor site were all closely associated with the PTT therapeutic efficacy. Therefore, the theranostic nanoplatform is a very promising strategy for targeted imaging-guided photothermal/chemo synergistic tumor therapy with high therapeutic efficacy and minimized side effects. STATEMENT OF SIGNIFICANCE: Breast cancer is the most frequent cancer in women. Herein, we successfully developed a light-controllable and HER2 targeted theranostic nanoparticels (PFH-PTX@PLGA/SPIO-Her) as a specific drug delivery nanoplatform to overcome the low accuracy of tumor detection and the low specificity of traditional chemo-therapeutic protocols. The study demonstrated that PFH-PTX@PLGA/SPIO-Her could actively target to breast cancer cells with positive HER2 expression. The biocompatible PFH-PTX@PLGA/SPIO-Her nanoparticles as both photoacoustic/ultrasound bimodal imaging agents, photothermal-conversion nanomaterials (photothermal hyperthermia) and controllable drug delivery nanoagents (optical droplet vaporization) have completely eradicated the tumor without severe side effects. The theranostic strategy not only integrates strengthens of traditional imaging or therapeutic modalities, but also paves a new way for the efficient cancer treatment by taking the advantage of quickly-developing nanomedicine.


Assuntos
Neoplasias da Mama/terapia , Sistemas de Liberação de Medicamentos/métodos , Hipertermia Induzida , Luz , Imagem Multimodal , Nanopartículas/química , Fototerapia , Animais , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Terapia Combinada , Dextranos/química , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Fluorcarbonetos/química , Humanos , Nanopartículas de Magnetita/química , Camundongos Nus , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Transição de Fase , Técnicas Fotoacústicas , Poliésteres/química , Polietilenoglicóis/química , Receptor ErbB-2/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Ultrassom
7.
Chin Med J (Engl) ; 131(12): 1472-1479, 2018 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-29893365

RESUMO

Background: LMNA-related muscular dystrophy can manifest in a wide variety of disorders, including Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), and LMNA-associated congenital muscular dystrophy (L-CMD). Muscle magnetic resonance imaging (MRI) has become a useful tool in the diagnostic workup of patients with muscle dystrophies. This study aimed to investigate whether there is a consistent pattern of MRI changes in patients with LMNA mutations in various muscle subtypes. Methods: Twenty-two patients with LMNA-related muscular dystrophies were enrolled in this study. MRI of the thigh and/or calf muscles was performed in them. The muscle MRI features of the three subtypes were compared by the Mann-Whitney U-test. The relationship between the clinical and MRI findings was also investigated by Spearman's rank analyses. Results: The present study included five EDMD, nine LGMD, and eight L-CMD patients. The thigh muscle MRI revealed that the fatty infiltration of the adductor magnus, semimembranosus, long and short heads of the biceps femoris, and vasti muscles, with relative sparing of the rectus femoris, was the predominant change observed in the EDMD, LGMD, and advanced-stage L-CMD phenotypes, although the involvement of the vasti muscles was not prominent in the early stage of L-CMD. At the level of the calf, six patients (one EDMD, four LGMD, and one L-CMD) also showed a similar pattern, in which the soleus and the medial and lateral gastrocnemius muscles were most frequently observed to have fatty infiltration. The fatty infiltration severity demonstrated higher scores associated with disease progression, with a corresponding rate of 1.483 + 0.075 × disease duration (X) (r = 0.444, P = 0.026). It was noteworthy that in six L-CMD patients with massive inflammatory cell infiltration in muscle pathology, no remarkable edema-like signals were observed in muscle MRI. Conclusions: EDMD, LGMD and advanced-staged L-CMD subtypes showed similar pattern of muscle MRI changes, while early-staged L-CMD showed somewhat different changes. Muscle MRI of L-CMD with a muscular dystrophy pattern in MRI provided important clues for differentiating it from childhood inflammatory myopathy. The fatty infiltration score could be used as a reliable biomarker for outcome measure of disease progression.


Assuntos
Imagem por Ressonância Magnética/métodos , Distrofia Muscular do Cíngulo dos Membros/diagnóstico por imagem , Distrofia Muscular de Emery-Dreifuss/diagnóstico por imagem , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Distrofias Musculares/diagnóstico por imagem , Adulto Jovem
8.
Artigo em Chinês | MEDLINE | ID: mdl-29737749

RESUMO

Low frequency sensorineural deafness is a common subtype of idiopathic sudden deafness. Certain patients suffered recurrent attacks without vertigo, much alike Meniere's disease. Few of them developed into definite Meniere's disease during long-term follow-up in many clinical studies. Although the pathophysiology of recurrent low frequency deafness is yet unknown, the desease is considered associated with early state of endolymphatic hydrops or migraine. Otologists shall be aware of its clinical course and careful explanation is necessary at time of initial informed consent.


Assuntos
Hidropisia Endolinfática/complicações , Perda Auditiva Neurossensorial/diagnóstico , Doença de Meniere/complicações , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Súbita , Humanos , Vertigem
9.
Parkinsonism Relat Disord ; 52: 62-68, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29606605

RESUMO

OBJECTIVE: Non-motor symptoms (NMS) are important prodromal characteristics of Parkinson's disease (PD). However, the incidence of NMS in first-degree relatives, such as siblings of PD patients, is still unknown. METHODS: A total of 98 PD patients of the Affiliated Hospital of Yangzhou University were recruited; 210 siblings of these patients were included in a first-degree relatives (FDR) group and 250 healthy individuals were included in a control group. Various scales were used to assess NMS, including depression, anxiety, cognitive function, sleep status, constipation, daytime sleepiness, Rapid-Eye-Movement Sleep Behavior Disorder (RBD), and Restless Legs Syndrome (RLS). RESULTS: NMS were more common in the PD group than the control group. The incidence of anxiety (OR = 3.434, 95%CI: 2.058-5.731, P < 0.001), depression (OR = 2.438, 95%CI: 1.289-4.609, P = 0.005), and RBD (OR = 4.120, 95%CI: 1.897-8.945, P < 0.001) was higher in the FDR group than the control group. There were non-significant differences in constipation, cognitive impairment, sleep disorder, daytime sleepiness, and RLS between the two groups. The incidence of RLS in FDR of PD with an age of onset <60 years was higher than in the controls (OR = 2.273, 95%CI: 1.107-4.667, P = 0.023). CONCLUSIONS: Siblings of PD are more likely to suffer from anxiety, depression and RBD than the general population. RLS is more common in siblings of PD with onset age<60 than in the general population. It is speculated that PD patients and their siblings have common pathogenic genetic factors and early living environment for neurodegeneration.


Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Doença de Parkinson/epidemiologia , Transtorno do Comportamento do Sono REM/epidemiologia , Síndrome das Pernas Inquietas/epidemiologia , Irmãos , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Medicine (Baltimore) ; 97(3): e9610, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29504988

RESUMO

There have no universally accepted criteria and have been established for classification of underactive bladder (UAB) at present. Thus, the study described the comprehensive clinical and urodynamic characteristics of UAB in patients with lower urinary tract symptoms.A total of 1726 patients (1259 men and 467 women; 6-88 years old) who were admitted to our center with a diagnosis of UAB were included in this retrospective study. It was due to the type of rehabilitation hospital, so higher percentage of neurological patients were included. The demographics, clinical characteristics, and urodynamic recordings were reviewed. The clinical characteristics and urodynamic findings of UAB were further classified.For the etiologic analysis, UAB with aging and without clear causes accounted for 11.5% of cases (199/1726), UAB with bladder outflow obstruction accounted for 2.6% (45/1726), and UAB acting on the nerve pathway of the voiding reflex accounted for 84.6% (1460/1726). There were a number of cases (1.3% [22/1726]) which had >2 factors assigned. For studies involving urodynamic findings and clinical symptoms, the percentage of patients with detrusor hyperreflexia with impaired contractility (DHIC), detrusor underactivity (DU), and acontractile detrusor (AcD) was 0.7%, 5.6%, and 93.7%, respectively.UAB can be classified into 4 types based on possible etiologic mechanisms (idiopathic, myogenic, neurogenic, and integrative). Based on urodynamic findings and symptoms, UAB can be classified into 3 types (DU, AcD, and DHIC). The classification of UAB can provide a reasonable basis for the future research.


Assuntos
Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/fisiopatologia , Doenças da Bexiga Urinária/diagnóstico , Doenças da Bexiga Urinária/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Urodinâmica , Adulto Jovem
11.
Chin Med J (Engl) ; 131(2): 144-150, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29336361

RESUMO

BACKGROUND: Clinically, it is difficult to differentiate multiple acyl-CoA dehydrogenase deficiency (MADD) from immune-mediated necrotizing myopathy (IMNM) because they display similar symptoms. This study aimed to determine whether muscle magnetic resonance imaging (MRI) could be used for differential diagnosis between MADD and IMNM. METHODS: The study evaluated 25 MADD patients, confirmed by muscle biopsy and ETFDH gene testing, and 30 IMNM patients, confirmed by muscle biopsy. Muscles were assessed for edema and fatty replacement using thigh MRI (tMRI). Degrees and distribution patterns of fatty infiltration and edema in gluteus maximus and thigh muscles were compared. RESULTS: Total fatty infiltration and edema scores (median, [Q1, Q3]) were 4.00 (1.00, 15.00) and 0 (0, 4.00) in MADD and 14.50 (8.00, 20.75) and 22.00 (16.75, 32.00) in IMNM, respectively, which were significantly more severe in IMNM than that in MADD (P = 0.000 and P = 0.004, respectively). Edema scores for gluteus maximus, long head of biceps femoris, and semimembranosus were significantly higher in IMNM than in MADD (all P = 0.000). Fatty infiltration scores for anterior and medial compartments were significantly more severe in IMNM than that in MADD (all P = 0.000). CONCLUSION: Different patterns of muscle involvement on tMRI can contribute to differential diagnosis between MADD and IMNM when clinical suspicions alone are insufficient, thereby reducing the need for muscle biopsy.


Assuntos
Imagem por Ressonância Magnética/métodos , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Miosite/diagnóstico por imagem , Adulto , Creatina Quinase/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência Múltipla de Acil Coenzima A Desidrogenase/patologia , Músculo Esquelético/patologia , Miosite/patologia
12.
Biosci Rep ; 37(4)2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-28733472

RESUMO

We investigated the effects of RNAi-mediated gene silencing of vascular endothelial growth factor (VEGF) on ultrafiltration failure (UFF) in rats with peritoneal dialysis (PD). Sprague-Dawley (SD) male rats were classified into normal, sham operation, and uremic model groups. Uremic rats were subcategorized into uremia, PD2, VEGF shRNA-2, vector-2, PD2 + Endostar, PD4, VEGF shRNA-4, Vector-4, and PD4 + Endostar groups. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG). mRNA and protein expressions of VEGF were detected using quantitative real-time PCR (qRT-PCR) and Western blotting. Immunohistochemistry was performed to detect microvessel density (MVD). Compared with the normal group, decreased UFV and increased MTG were observed in rest of the groups. Compared with the uremia group, UFV decreased, while MTG, expression of VEGFs, and number of new blood capillaries increased in the PD2, Vector-2, PD4, and Vector-4 groups. The PD4 and Vector-4 groups exhibited lower UFV and higher MTG than the PD2 group. In the VEGF shRNA-2, PD2 + Endostar, VEGF shRNA-4, and in PD4 + Endostar group increased UFV, reduced MTG and expression of VEGF, and decreased number of new blood capillaries were detected. Compared with the PD4 group, in the VEGF shRNA-4 and PD4 + Endostar groups, UFV increased, MTG and expression of VEGF decreased, and number of new blood capillaries reduced. VEGF expression was negatively correlated with UFV, but positively correlated with MTG. The results obtained in the study revealed that down-regulation of VEGF by RNAi could be a novel target approach for the treatment of UFF.


Assuntos
Regulação para Baixo , Hemofiltração/efeitos adversos , Diálise Peritoneal/efeitos adversos , Interferência de RNA , Uremia/metabolismo , Fator A de Crescimento do Endotélio Vascular/biossíntese , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Ultrafiltração , Uremia/genética , Uremia/terapia , Fator A de Crescimento do Endotélio Vascular/genética
13.
Chin Med J (Engl) ; 130(9): 1042-1048, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28469098

RESUMO

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small artery disease caused by NOTCH3 gene mutation. We performed enhanced depth imaging optical coherence tomography (EDI-OCT) to evaluate the retinal vessel changes in CADASIL patients and assessed their consonance with brain magnetic resonance imaging (MRI) findings. METHODS: Of 27 genetically confirmed patients and an equal number of controls were recruited at the Peking University First Hospital from January 2015 to August 2016. All patients underwent 7T-MRI of the brain. Fazekas score, number of small infarcts and microbleeds were evaluated. All patients and controls underwent EDI-OCT to measure subfoveal choroidal thickness (SFCT), inner and outer diameters as well as arterial and venous wall thickness, and arterial venous ratio of the inner (AVRin) and outer diameters (AVRout). The relation between retinal vessel changes and Fazekas scores, numbers of small infarcts, or microbleeds was analyzed. Paired t-test was used to compare the SFCT and retinal vessel measurement data between patients and controls. Spearman's correlation was used to investigate the correlation between retinal vessel changes and MRI lesions. RESULTS: In CADASIL patients, mean SFCT (268.37 ± 46.50 µm) and mean arterial inner diameter (93.46 ± 9.70 µm) were significantly lower than that in controls (P < 0.001,P = 0.048, respectively). Mean arterial outer diameter (131.74 ± 10.87 µm), venous inner (128.99 ± 13.62 µm) and outer diameter (164.82 ± 14.77 µm), and mean arterial (19.13 ± 1.85 µm) and venous (17.91 ± 2.76 µm) wall thickness were significantly higher than that in controls (P = 0.023,P = 0.004,P < 0.001,P < 0.001, respectively). Arterial inner diameter (rs= -0.39, P= 0.044), AVRin (rs= -0.65,P < 0.001), and AVRout (rs= -0.56, P= 0.002) showed a negative correlation with the number of small infarcts. Venous inner diameter (rs = 0.46, P= 0.016) showed a positive correlation with the number of small infarcts. Venous inner diameter (rs = 0.59, P= 0.002), outer diameter (rs = 0.47, P= 0.017), showed a positive correlation with the number of cerebral microbleeds (CMBs). AVRin (rs= -0.52, P= 0.007) and AVRout (rs= -0.40, P= 0.048) showed a negative correlation with the number of CMBs. CONCLUSIONS: Measurement of retinal vessels using EDI-OCT correlates moderately well with MRI parameters. EDI-OCT might be a useful evaluation tool for CADASIL patients.


Assuntos
Leucoencefalopatias/patologia , Imagem por Ressonância Magnética/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Encéfalo/metabolismo , CADASIL , Infarto Cerebral/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Receptor Notch3/genética , Vasos Retinianos/metabolismo
14.
Chin Med J (Engl) ; 130(9): 1049-1054, 2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28469099

RESUMO

BACKGROUND: X-linked Charcot-Marie-Tooth type 1 (CMT1X) disease is one of the most common forms of inherited neuropathy caused by mutations in the gap junction beta-1 protein (GJB1) gene (also known as connexin 32). This study presented the clinical and genetic features of a series of Chinese patients with GJB1 gene mutations. METHODS: A total of 22 patients from unrelated families, who were referred to Department of Neurology, Peking University First Hospital from January 2005 to January 2016, were identified with GJB1 mutations. Their clinical records and laboratory findings were retrospectively collected and reviewed. Mutations in the GJB1 gene were analyzed by targeted next-generation sequencing (NGS). Nucleotide alternations were confirmed with Sanger sequencing. RESULTS: The CMT1X patients predominantly showed distal muscle weakness of lower limbs with mild sensory disturbance. The mean age of onset was 15.6 ± 8.7 years (ranging from 1 year to 42 years). The sudden onset of cerebral symptoms appeared in four patients (18.2%); two were initial symptoms. One case had constant central nervous system (CNS) signs. There were 19 different heterozygous mutations, including 15 known mutations and four novel mutations (c.115G>T, c.380T>A, c.263C>A, and c.818_819insGGGCT). Among the 22 Chinese patients with CMT1X, the frequency of the GJB1 mutation was 4.5% in transmembrane domain 1 (TM1), 4.5% in TM2, 22.7% in TM3, 9.1% in TM4, 4.5% in extracellular 1 (EC1), 27.3% in EC2, 9.1% in intracellular loop, 13.6% in the N-terminal domain, and 4.5% in the C-terminal domain. CMT1X with CNS impairment appeared in five (22.7%) of these patients. CONCLUSIONS: This study indicated that CNS impairment was not rare in Chinese CMT1X patients. Mutations in the EC2 domain of the GJB1 gene were hotspot in Chinese CMT1X patients.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Conexinas/genética , Adolescente , Adulto , Sistema Nervoso Central/metabolismo , Doença de Charcot-Marie-Tooth/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Eletrofisiologia , Feminino , Genótipo , Humanos , Lactente , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Adulto Jovem
15.
Mol Med Rep ; 16(1): 143-150, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28535003

RESUMO

miR-1271 is a multifunctional post-translational modulator, which is involved in several diseases. However, the association between microRNA (miR)­1271 and fibronectin 1 (FN1) remains to be fully elucidated in neuroglioma. In the present study, it was hypothesized that a post­translational mechanism of miR­1271 regulates the expression of FN1 in the progression of neuroglioma. The present study aimed to investigate the clinical significance and underlying molecular mechanisms of miRNA­1271 in the development of glioma. The miR­1271 levels in glioma tissues and cell lines were assessed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). miR­1271 mimics and inhibitors were transfected to gain or loss of miR­1271 function. Cell proliferation was analyzed by using an MTT assay. The targeted genes were predicted by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The mRNA and protein levels were assessed by RT­qPCR and western blotting. The results showed that miR­1271 was downregulated in glioma tumor tissues and cell lines. In addition, it was demonstrated that low levels of miR­1271 in patients with glioma were correlated with low survival rate. In vitro, the cell viability was significantly suppressed following transfection with miRNA­1271 mimics and increased following transfection with the miRNA­1271 inhibitor. The miRNA­1271 mimics induced cell apoptosis and the miRNA­1271 inhibitor suppressed cell apoptosis in H4 and U251 cell lines. Furthermore, the 3'­untranslated region of FN1 was bound by miR­1271. Therefore, it was concluded that miR­1271 inhibited glioma cell growth by targeting FN1, and a low level of miR­1271 in glioma tumor tissues was associated with lower survival rates in patients with glioma.


Assuntos
Neoplasias Encefálicas/genética , Citocinas/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , MicroRNAs/genética , Interferência de RNA , Adulto , Idoso , Apoptose/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Fibronectinas , Expressão Gênica , Perfilação da Expressão Gênica , Genes Reporter , Glioma/metabolismo , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
16.
Blood Press Monit ; 22(3): 143-148, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28240683

RESUMO

BACKGROUND: Waist-to-height ratio (WHtR) is proposed as a simple and effective screening tool for abdominal obesity and cardiovascular disease risk factors. The present study examined the profiles of blood pressure (BP) among children and adolescents categorized by WHtR cutoffs. PATIENTS AND METHODS: A total of 28 074 (14 015 boys and 14 059 girls) students aged 7-17 years participated in the study. Height, waist circumference and BP of all patients were measured, and WHtR was calculated. Relatively high blood pressure (RHBP) status was defined as systolic BP and/or diastolic BP of at least the 95th percentile for age and sex. All patients were divided into three groups (low, moderate and high) according to their WHtR. BP level and the prevalence of RHBP among the three groups were compared. RESULTS: In both boys and girls, significant differences in BP level and the prevalence of RHBP were observed among the three groups (P<0.01). Children and adolescents aged 7-17 years in the 'high WHtR group' (≥0.5) had higher systolic BP and diastolic BP compared with those in the 'low WHtR group' (<0.4) by 6.07-11.49 and 3.28-6.34 mmHg for boys and 5.62-9.76 and 3.14-5.95 mmHg for girls; the 'high WHtR group' had the highest (34.02% for boys and 30.87% for girls) and the 'low WHtR group' had the lowest prevalence of RHBP (15.23% for boys and 12.53% for girls). CONCLUSION: High WHtR is associated with elevated BP. These findings emphasize the importance of the prevention of abdominal obesity to prevent future problems such as hypertension in children and adolescents.


Assuntos
Pressão Sanguínea , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Adolescente , Determinação da Pressão Arterial , Estatura , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade Abdominal/epidemiologia , Fatores de Risco , Circunferência da Cintura
17.
Mol Cancer ; 16(1): 17, 2017 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-28109288

RESUMO

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.


Assuntos
Adenocarcinoma/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , Interleucinas/genética , Neoplasias Pulmonares/genética , RNA Longo não Codificante/genética , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Análise por Conglomerados , Biologia Computacional/métodos , Modelos Animais de Doenças , Expressão Ectópica do Gene , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Perfilação da Expressão Gênica , Inativação Gênica , Histona Desmetilases/genética , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , Carga Tumoral
19.
Int J Cardiol ; 227: 89-93, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27855292

RESUMO

BACKGROUND: Childhood obesity has increased dramatically during the past decades, both in developing and developed countries. The present study examined the prevalence and regional disparities in general and central obesity among children and adolescents in Shandong, China. METHODS: A total of 30,459 students (15,249 boys and 15,210 girls) aged 7-18years participated in the study. Height, weight and waist circumference (WC) of all subjects were measured, body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. The BMI cutoff points recommended by the International Obesity Task Force (IOTF) were used to define general obesity. Central obesity was defined as WHtR≥0.5. Both BMI and WHtR were used to define three types of obesity as follows: general obesity only, central obesity only and combined obesity. RESULTS: The overall prevalences of general obesity only, central obesity only and combined obesity were 10.99, 8.47 and 8.70% for boys and 9.47, 5.12 and 3.19% for girls, respectively. The sum of the prevalence of the three types of obesity was 28.16% for boys and 17.78% for girls, boys had higher prevalence of obesity than girls (P<0.01). Substantial urban-rural and regional disparities exist in childhood obesity, children and adolescents from urban, coastal and high socioeconomic status (SES) districts showed a higher prevalence of obesity than their counterparts from rural, inland and low SES districts (P<0.01). CONCLUSION: The widespread prevalence of obesity in children and adolescents has become an important public health concern. Results from this study also suggested that the additional measurement of WC (WHtR) is better than BMI alone to identify obese individuals, distinguishing the types of obesity and examining the prevalence of various types of obesity is useful in practice.


Assuntos
Disparidades nos Níveis de Saúde , Obesidade Abdominal/diagnóstico , Obesidade Abdominal/epidemiologia , População Rural , Classe Social , População Urbana , Adolescente , Criança , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Obesidade/diagnóstico , Obesidade/economia , Obesidade/epidemiologia , Obesidade Abdominal/economia , Prevalência , População Urbana/tendências , Circunferência da Cintura/fisiologia
20.
Oncotarget ; 8(3): 5233-5246, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-28029651

RESUMO

Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11.2 and 2398 nt in length. Firstly, we found that DUXAP10 was significantly up-regulated in 93 human NSCLC tissues and cell lines, and increased DUXAP10 was associated with patients poorer prognosis and short survival time. Furthermore, the loss and gain of functional studies including growth curves, migration, invasion assays and in vivo studies verify the oncogenic roles of DUXAP10 in NSCLC. Finally, the mechanistic experiments indicate that DUXAP10 could interact with Histone demethylase Lysine specific demethylase1 (LSD1) and repress tumor suppressors Large tumor suppressor 2 (LATS2) and Ras-related associated with diabetes (RRAD) transcription in NSCLC cells. Taken together, these findings demonstrate DUXAP10 exerts the oncogenic roles through binding with LSD1 and epigenetic silencing LATS2 and RRAD expression. Our investigation reveals the novel roles of pseudogene in NSCLC, which may serve as new target for NSCLC diagnosis and therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Histona Desmetilases/genética , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/genética , RNA Longo não Codificante/genética , Proteínas Supressoras de Tumor/genética , Proteínas ras/genética , Células A549 , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Masculino , Camundongos , Prognóstico , Pseudogenes , Análise de Sobrevida , Regulação para Cima
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