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1.
Artigo em Inglês | MEDLINE | ID: mdl-32215561

RESUMO

BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective and fast-acting treatment for depression used in the clinic. Its mechanism of therapeutic action remains uncertain. Previous studies have focused on documenting neuroplasticity in the early phase following electroconvulsive seizures (ECS), an animal model of ECT. Here, we investigate whether changes in synaptic plasticity and non-neuronal plasticity (vascular and mitochondria) are sustained 3 months after repeated ECS trial. METHODS: ECS or sham treatment was given daily for one day or 10 days to a genetic animal model of depression: the Flinders Sensitive and Resistant Line (FSL/FRL) rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and length of microvessels in the hippocampus 24 hours after a single ECS, 3 months after 10 ECS treatments (one a day for 10 days) and sham-treatment. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) protein levels were quantified with immunohistochemistry. Results: A single ECS treatment significantly increased the volume of hippocampal CA1-stratum radiatum (SR), the total length of microvessels, mitochondria number and synapse number. The observed changes were sustained as shown in the multiple ECS treatment group analyzed 3 months after the last of 10 ECS treatments. CONCLUSION: A single ECS caused rapid effects of synaptic plasticity and non-neuronal plasticity, while repeated ECS induced long-lasting changes in the efficacy of synaptic plasticity and non-neuronal plasticity at least up to 3 months after ECS.

2.
EBioMedicine ; 52: 102618, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31982829

RESUMO

BACKGROUND: The retinal pigment epithelium (RPE) has the potential to regenerate the entire neuroretina upon retinal injury in amphibians. In contrast, this regenerative capacity has been lost in mammals. The reprogramming of differentiated somatic cells into induced pluripotent stem cells (iPSCs) by viral transduction of exogenous stem cell factors has triggered a revolution in regenerative medicine. However, the risks of potential mutation(s) caused by random viral vector insertion in host genomes and tumor formation in recipients hamper its clinical application. One alternative is to immortalize adult stem cells with limited potential or to partially reprogram differentiated somatic cells into progenitor-like cells through non-integration protocols. METHODS: Sphere-induced RPE stem cells (iRPESCs) were generated from adult mouse RPE cells. Their stem cell functionality was studied in a mouse model of retinal degeneration. The molecular mechanism underlying the sphere-induced reprogramming was investigated using microarray and loss-of-function approaches. FINDINGS: We provide evidence that our sphere-induced reprogramming protocol can immortalize and transform mouse RPE cells into iRPESCs with dual potential to differentiate into cells that express either RPE or photoreceptor markers both in vitro and in vivo. When subretinally transplanted into mice with retinal degeneration, iRPESCs can integrate to the RPE and neuroretina, thereby delaying retinal degeneration in the model animals. Our molecular analyses indicate that the Hippo signaling pathway is important in iRPESC reprogramming. INTERPRETATION: The Hippo factor Yap1 is activated in the nuclei of cells at the borders of spheres. The factors Zeb1 and P300 downstream of the Hippo pathway are shown to bind to the promoters of the stemness genes Oct4, Klf4 and Sox2, thereby likely transactivate them to reprogram RPE cells into iRPESCs. FUND: National Natural Science Foundation of China and the National Institute of Health USA.

3.
Brain Res ; 1727: 146546, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715144

RESUMO

Many studies suggest that the hippocampus is involved in the pathophysiology of psychiatric disorders, especially major depressive disorder (MDD) and schizophrenia. Especially, in vivo imaging studies indicate that the volume of hippocampus may be reduced in both disorders. Moreover, suicide may have a unique neurobiology. The aim of the present study is to investigate if depression, schizophrenia or suicide is associated with reduced postmortem volume of the hippocampal formation and/or changes in the numbers of neurons and/or glial cells in the different subregions of the hippocampus. We studied postmortem brain samples from 10 subjects with schizophrenia, 8 subjects with major depression, 11 suicide subjects with a history of depressive disorder, and 10 control subjects with no history of psychiatric or neurological diseases. The total volume and numbers of neurons and glial cells were estimated for the main hippocampal subregions using design-unbiased stereological techniques. We found the total volume and total numbers of neurons and glial cells similarly reduced by approximately 20% to 35% in depression and schizophrenia subjects relative to control subjects across all hippocampal regions. In suicide subjects, we only found increased neuron number in CA2/3 subregion. The volume and number of cells are reduced in depression and schizophrenia subjects relative to control subjects across all hippocampal regions. Our findings imply that the hippocampus may be a common site of pathophysiology in depression and schizophrenia. Community living suicide subjects seem to differ in hippocampal neurobiology compared to hospitalized subjects dying with MDD without suicide.

4.
Huan Jing Ke Xue ; 41(1): 430-437, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854946

RESUMO

In order to study the source appointment of heavy metals in agricultural soils of the Jiulong River Basin, Fujian Province, China. 71 agricultural soil samples were collected in July 2017. The concentrations of heavy metals in agricultural soils were determined by inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrometry (AFS). Here, we use a positive matrix factorization (PMF) model for the source appointment of heavy metals in the sampled soils. The results showed that most of the heavy metal concentrations in the sampled agricultural soils were higher than soil background concentrations for the Fujian Province. The concentrations of Cd, Zn, Pb, and Cu in some soil samples were greater than the screening value of the Chinese soil pollution risk levels for agricultural land (GB 15618-2018). The spatial distributions of heavy metals showed a moderate variation across three regions of the study area (i.e., the North River watershed, West River watershed, and the estuary area). The highest concentration of Cr, Ni, Cu, Zn, and Cd were found in Longyan City (North River watershed), the highest concentrations of Pb were found in the West River watershed, and the highest concentrations of Co, Hg, and As were found in the estuary area. The non-negative properties of the source component spectrum and source contribution rate (obtained by the PMF model), as well as the significant correlation between the measured and PMF predicted concentrations, indicated that the results of the PMF model were relatively reasonable and can meet research needs. The source apportionment results of the PMF model showed that natural sources, agricultural sources, coal combustion, and industrial sources were the four major potential sources for heavy metals in the sampled agricultural soils, contributing 37.0%, 26.7%, 17.6%, and 18.7%, respectively.


Assuntos
Monitoramento Ambiental , Metais Pesados/análise , Poluentes do Solo/análise , China , Cidades , Rios
5.
Sci Rep ; 9(1): 16058, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690770

RESUMO

Tremendous efforts have been made to explore biomarkers for classification and grading on gliomas. The goal of this study was to identify more molecular features that are associated with clinical outcomes by comparing the genomic profiles of primary and recurrent gliomas and determine potential recurrence leading factors that are significantly enriched in relapse tumors. Hybrid capture based next generation sequencing (NGS) analysis was performed on 64 primary and 17 recurrent glioma biopsies. Copy number variation (CNV) was more frequent in recurrent tumors and CDKN2A/B loss was significantly enriched. In addition, overall mutations in cell cycle pathway are more common in relapse tumors. The patterns of gene sets, including IDH1/TERT and IDH1/TP53 exhibited significant difference between the groups. Survival analysis uncovered the worse disease-free survival (DFS) and overall survival (OS) associated with altered copy number and excessive activation of CELL CYCLE pathway. High Tumor Mutation Burden (TMB) was also a biomarker with great potential for poor prognosis. The assessment of genomic characteristics in primary versus recurrent gliomas aids the discovery of potential predictive biomarkers. The prognostic value of TMB in gliomas was raised for the first time.

6.
Asian J Androl ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31571639

RESUMO

Testosterone (T) plays a crucial role in spermatogenesis because extremely low levels of intratesticular T lead to correspondingly low serum levels of total T (tT), severe disorders of spermatogenesis, and male sterility. However, there is little consensus on the lower limits of serum tT in proven fertile men undergoing assisted reproductive technology treatments in Chinese or other Asian populations. We aimed to establish the reference range of serum tT based on a population of 868 fertile Chinese men undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) treatments. We defined a fertile man as having had a live baby with his partner as recorded in our IVF registration system. The lower limits of serum tT were established using a Siemens IMMULITE 2000 chemiluminescent system. The 1st, 2.5th, and 5th percentiles and their 95% confidence intervals (CIs) were 3.6 (95% CI: 2.7-4.1) nmol l-1, 4.3 (95% CI: 4.1-5.0) nmol l-1, and 5.6 (95% CI: 4.8-5.8) nmol l-1, respectively. Using the linear correlation of serum tT between the Siemens platform and a liquid chromatography-tandem mass spectrometry platform, the calculated lower limits of serum tT were also established for fertile Chinese men undergoing IVF/ICSI-ET treatments, which will benefit the clinical diagnosis and treatment of male infertility during such procedures.

7.
Arch Physiol Biochem ; : 1-7, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31274018

RESUMO

Hypoxia inducible factor subtype 1α (HIF-1α) in retinal tissues is involved in the development of glaucoma. This study examined the role played by mammalian target of rapamycin (mTOR) in regulating expression of HIF-1α and its downstream pathway, vascular endothelial growth factor (VEGF). Glaucoma was induced by chronic elevation of intraocular pressure using laser burns in rats. ELISA and western blot analysis were employed to determine the levels of HIF-1α, VEGF and mTOR in retinal tissues of eyes with high intraocular pressure. In results, HIF-1α, VEGF and VEGF receptor subtype 2 were increased in laser eyes. The p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4, p70 ribosomal S6 protein kinase 1 were also amplified in retina of laser eyes. Blocking mTOR using rapamycin attenuated HIF-1α-VEGF pathways, accompanied with downregulation of apoptotic Caspase-3. Our data revealed potential signalling pathways engaged in the development of glaucoma, including the activation of mTOR and HIF-1α-VEGF mechanism.

8.
World Neurosurg ; 131: e23-e31, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31238169

RESUMO

BACKGROUND: Intracranial aneurysm (IA) represents a cerebrovascular disorder that featured by dilation or bulging of the weakened blood vessel wall. When it ruptures, an IA leads to subarachnoid hemorrhage with high disability and mortality rates. Despite the numerous studies focusing on IA ruptures, little research on IA pathogenesis has been reported. In this study, we aimed to reveal key genes related to IA formation. METHODS: Four datasets from Gene Expression Omnibus data were downloaded, normalized, and separated into the IA group and the normal vessel control group for analyses. We screened for differentially expressed genes (DEGs) between groups and conducted functional enrichment, pathway enrichment, and gene set enrichment analysis analyses among significant DEGs. RESULTS: according to our analyses, significant DEGs majorly associate with smooth muscle system and the complement system. Among all DEGs, 5 down-regulated genes (MYH11, CNN1, MYOCD, ACTA1, and LMOD1) and 3 up-regulated genes (C1QB, C3AR1, and VSIG4) are most relevant in IA formation. CONCLUSIONS: Key DEGs identified in this study are related to IA pathogenesis. Among identified DEGs, LMOD1 is the most significant and merits more attention.


Assuntos
Aneurisma Intracraniano/genética , Actinas/genética , Autoantígenos/genética , Proteínas de Ligação ao Cálcio/genética , Estudos de Casos e Controles , Complemento C1q/genética , Proteínas do Sistema Complemento/genética , Proteínas do Citoesqueleto/genética , Regulação para Baixo , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Proteínas dos Microfilamentos/genética , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Cadeias Pesadas de Miosina/genética , Proteínas Nucleares/genética , Receptores de Complemento/genética , Transativadores/genética , Regulação para Cima , Remodelação Vascular/genética
9.
Front Biosci (Landmark Ed) ; 24: 1426-1439, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136988

RESUMO

miRNA-21 (miR-21) is overexpressed in various human cancers. Here, we show that miR-21 is overexpressed in human Non-Small Cell Lung Cancer (NSCLC)  and that its up or down-regulation, respectively, increases or decreases cyclin D1 and cyclin E1 expression and coordinately promotes or inhibits proliferation of cancer cells. The perturbations of miR-21 also dramatically reduces or increases epithelial to mesenschymal transition (EMT). We show that regulation of proliferation and EMT are directed by PTEN/Akt/GSK3 beta signaling axis by regulating the expression of invasion markers including E-cadherin, vimentin, snail, slug and beta-catenin. Together, these findings show that miR-21 is a potential target for the development of treatment for NSCLC forms of human lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Transdução de Sinais/genética , Células A549 , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Ciclinas/genética , Ciclinas/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
10.
Mol Neurobiol ; 56(11): 7368-7379, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31037646

RESUMO

When administered as a single subanesthetic dose, the N-methyl-D-aspartate (NMDA) receptor antagonist, ketamine, produces rapid (within hours) and relatively sustained antidepressant actions even in treatment-resistant patients. Preclinical studies have shown that ketamine increases dendritic spine density and synaptic proteins in brain areas critical for the actions of antidepressants, yet the temporal relationship between structural changes and the onset of antidepressant action remains poorly understood. In this study, we examined the effects of a single dose of S-ketamine (15 mg/kg) on dendritic length, dendritic arborization, spine density, and spine morphology in the Flinders Sensitive and Flinders Resistant Line (FSL/FRL) rat model of depression. We found that already 1 h after injection with ketamine, apical dendritic spine deficits in CA1 pyramidal neurons of FSL rats were completely restored. Notably, the observed increase in spine density was attributable to regulation of both mushroom and long-thin spines. In contrast, ketamine had no effect on dendritic spine density in FRL rats. On the molecular level, ketamine normalized elevated levels of phospho-cofilin and the NMDA receptor subunits GluN2A and GluN2B and reversed homer3 deficiency in hippocampal synaptosomes of FSL rats. Taken together, our data suggest that rapid formation of new spines may provide an important structural substrate during the initial phase of ketamine's antidepressant action.

11.
World Neurosurg ; 126: e1069-e1074, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878755

RESUMO

BACKGROUND: Inferior petrosal sinus (IPS) has been commonly adopted as a route for embolizing cavernous dural arteriovenous fistula (cDAVF). According to previous anatomical studies, >90% of persons have an IPS. Because the exact confluence position of the IPS with an internal jugular vein can be difficult to obtain using preoperative digital subtraction angiography (DSA), catheterizing into the IPS during endovascular treatment can sometimes be very difficult. Because the anatomical information has not been attainable, this route has not been as widely used. Thus, methods remain to be developed to allow the IPS to play its due role in the embolization of cDAVF. METHODS: Seven cases of cDAVF were diagnosed by DSA. The 7 patients also underwent preoperative computed tomography angiography (CTA) and were treated by transvenous embolization. RESULTS: Compared with DSA, the confluence position of the IPS with the internal jugular vein was easier to find using preoperative CTA in 6 cases. Based on this anatomical information, 6 cases were successfully embolized via the IPS route and 1 via the superior ophthalmic vein route. CONCLUSIONS: Detailed anatomical information of the IPS can be obtained from preoperative CTA images. Thus, CTA can help localize the IPS and allow for embolization of cDAVF via the IPS route.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Cavidades Cranianas/diagnóstico por imagem , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Transl Stroke Res ; 10(6): 719-728, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30820847

RESUMO

Our previous study indicated that nicotinamide phosphoribosyltransferase (NAMPT) is released from cells and might be an important extracellular neuroprotective factor in brain ischemia. Here, we tested whether NAMPT protects against ischemic brain injury when administered directly into the intracerebroventricular (ICV) compartment of the cranium. Recombinant NAMPT protein (2 µg) was delivered ICV in mice subjected to 45-min middle cerebral artery occlusion (MCAO), and the effects on infarct volume, sensorimotor function, microglia/macrophage polarization, neutrophil infiltration, and BBB integrity were analyzed. The results indicate that ICV administration of NAMPT significantly reduced infarct volume, retained its beneficial properties even when ICV administration was delayed by 6 h after MCAO, and improved neurological outcomes. NAMPT treatment inhibited pro-inflammatory microglia/macrophages, promoted microglia/macrophage polarization toward the anti-inflammatory phenotype, and reduced the infiltration of neutrophils into the perilesional area after brain ischemia. In vitro studies indicated that multiple pro-inflammatory microglial markers/cytokines were downregulated while multiple anti-inflammatory microglial markers/cytokines were induced in primary microglial cultures treated with NAMPT protein. NAMPT treatment also fortified the blood-brain barrier (BBB), as shown by reduced extravascular leakage of the small-molecule tracer Alexa Fluor 555 Cadaverine and larger-sized endogenous IgGs into brain parenchyma. Thus, NAMPT may protect against ischemic brain injury partly through a novel anti-inflammatory mechanism, which in turn maintains BBB integrity and reduces the infiltration of peripheral inflammatory cells. Taken together, these results provide validation of recombinant NAMPT delivery into the extracellular space as a potential neuroprotective strategy for stroke.

13.
Zhongguo Gu Shang ; 32(1): 22-27, 2019 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-30813663

RESUMO

OBJECTIVE: To explore clinical efficacy of limited external fixation with plastic paperboard in treating senile proximal comminuted humeral fracture. METHODS: From June 2015 to December 2017, 32 senile patients with proximal comminuted fracture of humerus were treated with plasticized cardboard after manual external fixation. Among them, including 13 males and 19 females aged from 55 to 85 years old with an average of(68.22±8.36) years old; 18 patients on the left side and 14 patients on the right side; all patients were regularly review shoulder X-rays and performed appropriate functional exercises. Constant-Murley shoulder joint scoring was used to evaluate clinical effects. RESULTS: Thirty-two patients were followed up for 3 to 12 months with an average of (4.97±2.39) months. All patients were underwent functional exercise under guidance of physicians. Nine patients were treated with topical Chinese herbal moist heat compresses to promote shoulder function recovery. Thirty-one patients were obtained fracture healing, the time ranged from 5 to 12 weeks with an average of(7.44±1.72)weeks. One patient was not healed due to comminuted fracture of fracture end and the separation was large, the blood supply to humeral head was insufficient for necrosis absorption. Postoperative Constant-Murley shoulder score at 3 months was 87.56±6.93; 15 patients got excellent results, 14 good, 2 fair and 1 poor. CONCLUSIONS: Limited external fixation with plastic paperboard for the treatment of senile proximal comminuted humeral fracture could ensure biomechanical stability of fracture, promote early recovery of shoulder joint function and shorten recovery time.


Assuntos
Fraturas Cominutivas , Fraturas do Úmero , Fraturas do Ombro , Idoso , Idoso de 80 Anos ou mais , Feminino , Fixação Interna de Fraturas , Fraturas Cominutivas/cirurgia , Humanos , Fraturas do Úmero/cirurgia , Masculino , Pessoa de Meia-Idade , Plásticos , Resultado do Tratamento
14.
Proc Natl Acad Sci U S A ; 116(10): 4643-4650, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30760601

RESUMO

Ubiquitin C-terminal hydrolase L1 (UCHL1) is a unique brain-specific deubiquitinating enzyme. Mutations in and aberrant function of UCHL1 have been linked to many neurological disorders. UCHL1 activity protects neurons from hypoxic injury, and binding of stroke-induced reactive lipid species to the cysteine 152 (C152) of UCHL1 unfolds the protein and disrupts its function. To investigate the role of UCHL1 and its adduction by reactive lipids in inhibiting repair and recovery of function following ischemic injury, a knock-in (KI) mouse expressing the UCHL1 C152A mutation was generated. Neurons derived from KI mice had less cell death and neurite injury after hypoxia. UCHL1 C152A KI and WT mice underwent middle cerebral artery occlusion (MCAO) or sham surgery. White matter injury was significantly decreased in KI compared with WT mice 7 d after MCAO. Histological analysis revealed decreased tissue loss at 21 d after injury in KI mice. There was also significantly improved sensorimotor recovery in postischemic KI mice. K63- and K48-linked polyubiquitinated proteins were increased in penumbra of WT mouse brains but not in KI mouse brains at 24 h post MCAO. The UCHL1 C152A mutation preserved excitatory synaptic drive to pyramidal neurons and their excitability in the periinfarct zone; axonal conduction velocity recovered by 21 d post MCAO in KI mice in corpus callosum. These results demonstrate that UCHL1 activity is an important determinant of function after ischemia and further demonstrate that the C152 site of UCHL1 plays a significant role in functional recovery after stroke.

15.
J Clin Anesth ; 53: 70-73, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30343226

RESUMO

STUDY OBJECTIVE: To calculate the stomach volume according to the antral area in pregnant women. DESIGN: Prospective observational study. SETTING: One of the maternity units in our hospital. PATIENTS: 24 singleton pregnancy women, over 18-year-old, non-laboring, gestational age ≥ 36 weeks, ASA physical status I to II were involved in our study. INTERVENTIONS AND MEASUREMENTS: An ultrasound assessment of the antrum was performed to the pregnant women after 8 hours fasting for the first time. Those lacking of visualization of any gastric contents in the antrum in both the supine and the right lateral decubitus positions were included in our study. Thereafter 50 ml of water was ingested, 4 times, 200 ml in total. The antrum area was examined 2mins after each 50 ml ingest of water. MAIN RESULTS: A high correlation between CSA and volume of liquid ingested (r = 0.90,P < 0.01) was found. We can construct a formula for the prediction of volume values based on the measured CSA values and demographic variables. The equation is: Volumeml=270.76+13.68∗CSA-1.20∗gestationalage CONCLUSIONS: Bedside antrum area examination by ultrasonography can provide quantitative information for the assessment of the gastric content and volume in the pregnant women. We can calculate the actual stomach capacity according to the CSA of the gastric antrum.


Assuntos
Conteúdo Gastrointestinal/diagnóstico por imagem , Antro Pilórico/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Gravidez , Estudos Prospectivos , Ultrassonografia
16.
Neurobiol Dis ; 124: 118-132, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30439443

RESUMO

Intracranial atherosclerosis (ICAS) is a progressive pathological process that causes progressive stenosis and cerebral hypoperfusion and is a major cause of stroke occurrence and recurrence around the world. Multiple factors contribute to the development of ICAS. Angiography imaging techniques can improve the diagnosis of and the selection of appropriate treatment regimens for ICAS. Neither aggressive medication nor endovascular interventions can eradicate stroke recurrence in patients with ICAS. Non-pharmacological therapies such as remote ischemic conditioning and hypothermia are emerging. Comprehensive therapy with medication in combination with endovascular intervention and/or non-pharmacological treatment may be a potential strategy for ICAS treatment in the future. We summarized the epidemiology, pathophysiological mechanisms, risk factors, biomarkers, imaging and management of ICAS.


Assuntos
Arteriosclerose Intracraniana/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Humanos , Arteriosclerose Intracraniana/complicações , Fatores de Risco , Acidente Vascular Cerebral/etiologia
17.
Transl Stroke Res ; 10(3): 279-286, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30173313

RESUMO

The terminal complement complex C5b-9 plays an important role in acute ischemic stroke (AIS) and carotid atherosclerosis. However, the associations between serum C5b-9, the severity and outcome of AIS, and the stability of carotid plaques have not been well investigated. In this clinical study, 70 patients with AIS and 70 healthy controls were enrolled. Serum C5b-9 levels at 72 h after stroke onset were measured by enzyme-linked immunosorbent assay (ELISA). Infarct size, the National Institutes of Health Stroke Scale (NIHSS), the 90-day modified Rankin Scale (mRS), and carotid plaque and stenosis were evaluated. Serum C5b-9 levels were significantly higher in AIS patients than in healthy controls (p < 0.001) and were correlated with infarction sizes (p = 0.045) and the NIHSS (P = 0.035). Furthermore, 90-day mRS analysis demonstrated that the patients with poor outcomes had higher serum C5b-9 levels than those with good outcomes (P < 0.001). Moreover, serum C5b-9 levels in AIS patients with unstable carotid plaques were much higher than in those with stable carotid plaques (P = 0.009). Multivariate logistic regression indicated that C5b-9 could be an independent risk factor for AIS (P < 0.001) and unstable carotid plaques (P = 0.015). Therefore, complement complex C5b-9 may be a potential biomarker in predicting the severity and outcome, as well as the stability of carotid plaques, in AIS patients.


Assuntos
Isquemia Encefálica/sangue , Estenose das Carótidas/sangue , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Estenose das Carótidas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Resultado do Tratamento
18.
Mediators Inflamm ; 2019: 7415891, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933542

RESUMO

The association of residual myometrium thickness (RMT) and scar defect depth (D) with menstrual abnormalities and the effectiveness of vaginal repair remain to be determined in patients with cesarean section scar diverticulum (CSD). To assess the value of ultrasound to predict vaginal repair effectiveness. This was a retrospective study of patients with CSD treated with vaginal repair between 01/2014 and 02/2016 at Shanghai First Maternity and Infant Hospital (Tongji University). Transvaginal ultrasound was performed before and 3 months after surgical repair. RMT, D, scar defect length (L), and scar defect width (W) were measured. Width (W), D, and L increased along the duration of menstrual period (P < 0.05). When the menstrual extension time was ≥15 days, RMT/D and RMT/(RMT + D) were smaller than in patients with period <15 days (P < 0.05). L was the most positively correlated ultrasonic parameter with menstrual prolongation (r = 0.492). RMT/D and RMT/(RMT + D) were negatively correlated with prolonged menstruation (r = -0.304 and -0.305, respectively). RMT/D and RMT/(RMT + D) were associated with the disappearance of CSD after vaginal repair (P < 0.05). The cutoff value of RMT/(RMT + D) was 0.496, with sensitivity of 53.0% and specificity of 61.4%. L of CSD is closely correlated with menstrual extension but has no relationship with the effectiveness of surgery. RMT/(RMT + D) is correlated with menstrual extension time ≥15 days and the effectiveness of vaginal repair.

19.
Am J Clin Exp Urol ; 6(5): 172-181, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510969

RESUMO

Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation. The TRAMP SV40 T antigen transgenic mouse is a model for PCa. The expression of SV40 T-antigen is driven by the androgen-responsive, prostate specific, Probasin promoter. It has been recognized that in this model, T-antigen is still expressed even after androgen ablation. It is unclear how the androgen-responsive Probasin promoter remains active and drives the expression of T-antigen in these tumors. In our study, we found that the expression of Foxa2, a forkhead transcription factor that is expressed in embryonic prostate and advanced stage prostate cancer, is co-expressed in T-antigen positive cells. To test if Foxa2 activates AR-responsive promoters and promotes the expression of T-antigen, we established the prostate epithelial cells that stably express Foxa2, NeoTag1/Foxa2 cells. Neotag1 cells were derived from the Probasin promoter driven SV40 T-antigen transgenic mouse. We found ectopic expression of Foxa2 drives the T-antigen expression regardless of the presence of androgens. Using this model system, we further explored the mechanism that activates AR-responsive promoters in the absence of androgens. Chromatin immunoprecipitation revealed the occupancy of both H3K27Ac, an epigenetic mark of an active transcription, and Foxa2 at the known AR target promoters, Probasin and FKBP5, in the absence of androgen stimulation. In conclusion, we have identified a mechanism that enables PCa to retain the AR signaling pathway after androgen ablation.

20.
World Neurosurg ; 115: 266-273, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29730105

RESUMO

BACKGROUND: Outcomes of minimally invasive surgery (MIS) versus conventional craniotomy (CC) for patients with spontaneous supratentorial intracerebral hemorrhage (SICH) have not been compared previously. We reviewed the current evidence regarding the safety and efficacy of MIS compared with CC in patients with SICH. METHODS: We conducted a meta-analysis of studies comparing MIS and CC in patients with computed tomography-confirmed SICH published between January 2000 and April 2018 in MEDLINE, Embase, and the Cochrane Controlled Trials Register based on PRISMA inclusion and exclusion criteria. Binary outcomes comparisons between MIS and CC were described using odds ratios (ORs). RESULTS: Five randomized controlled trials (RCTs) and 9 prospective controlled studies (non-RCTs), involving a total of 2466 patients, met our inclusion criteria. There was a statistically significant difference in mortality rate between MIS and CC (OR, 0.76; 95% confidence interval [CI], 0.60-0.97). MIS was associated with a lower rate of rebleeding (OR, 0.42; 95% CI, 0.28-0.64) and a higher rate of good recovery compared with CC (OR, 2.27; 95% CI, 1.34-3.83). CONCLUSIONS: Patients with SICH may benefit more from MIS than CC. Our study could help clinicians optimize treatment strategies in SICH.


Assuntos
Hemorragia Cerebral/cirurgia , Craniotomia/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Craniotomia/mortalidade , Craniotomia/normas , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/mortalidade , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
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