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Dynamic functional networks (DFN) have considerably advanced modelling of the brain communication processes. The prevailing implementation capitalizes on the system and network-level correlations between time series. However, this approach does not account for the continuous impact of non-dynamic dependencies within the statistical correlation, resulting in relatively stable connectivity patterns of DFN over time with limited sensitivity for communication dynamic between brain regions. Here, we propose an activation network framework based on the activity of functional connectivity (AFC) to extract new types of connectivity patterns during brain communication process. The AFC captures potential time-specific fluctuations associated with the brain communication processes by eliminating the non-dynamic dependency of the statistical correlation. In a simulation study, the positive correlation (r=0.966,p<0.001) between the extracted dynamic dependencies and the simulated "ground truth" validates the method's dynamic detection capability. Applying to autism spectrum disorders (ASD) and COVID-19 datasets, the proposed activation network extracts richer topological reorganization information, which is largely invisible to the DFN. Detailed, the activation network exhibits significant inter-regional connections between function-specific subnetworks and reconfigures more efficiently in the temporal dimension. Furthermore, the DFN fails to distinguish between patients and healthy controls. However, the proposed method reveals a significant decrease (p<0.05) in brain information processing abilities in patients. Finally, combining two types of networks successfully classifies ASD (83.636 % ± 11.969 %,mean±std) and COVID-19 (67.333 % ± 5.398 %). These findings suggest the proposed method could be a potential analytic framework for elucidating the neural mechanism of brain dynamics.
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Transtorno do Espectro Autista , COVID-19 , Humanos , Imageamento por Ressonância Magnética/métodos , Vias Neurais/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , ComunicaçãoRESUMO
Chemical recycling of polymers to monomers presents a promising solution to the escalating crisis associated with plastic waste. Despite considerable progress made in this field, the primary efforts have been focused on redesigning new monomers to produce readily recyclable polymers. In contrast, limited research into the potential of seemingly "non-polymerizable" monomers has been conducted. Herein, we propose a paradigm that leverages a "chaperone"-assisted strategy to establish closed-loop circularity for a "non-polymerizable" α, ß-conjugated lactone, 5,6-dihydro-2H-pyran-2-one (DPO). The resulting PDPO, a structural analogue of poly(δ-valerolactone) (PVL), exhibits enhanced thermal properties with a melting point (Tm) of 114 °C and a decomposition temperature (Td,5%) of 305 °C. Notably, owing to the structural similarity between DPO and δ-VL, the copolymerization generates semi-crystalline P(DPO-co-VL)s irrespective of the DPO incorporation ratio. Intriguingly, the inherent C=C bonds in P(DPO-co-VL)s enable their convenient post-functionalization via Michael-addition reaction. Lastly, PDPO was demonstrated to be chemically recyclable via ring-closing metathesis (RCM), representing a significant step towards the pursuit of enabling the closed-loop circularity of "non-polymerizable" lactones without altering the ultimate polymer structure.
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BACKGROUND: Quantitative magnetic resonance imaging (MRI) is considered an objective biomarker of Duchenne muscular dystrophy (DMD), but the longitudinal progression of MRI biomarkers in gluteal muscle groups and their predictive value for future motor function have not been described. OBJECTIVE: To explore MRI biomarkers of the gluteal muscle groups as predictors of motor function decline in DMD by characterizing the progression over 12 months. MATERIALS AND METHODS: A total of 112 participants with DMD were enrolled and underwent MRI examination of the gluteal muscles to determine fat fraction and longitudinal relaxation time (T1). Investigations were based on gluteal muscle groups including flexors, extensors, adductors, and abductors. The North Star Ambulatory Assessment and timed functional tests were performed. All participants returned for follow-up at an average of 12 months and were divided into two subgroups (functional stability/decline groups) based on changes in timed functional tests. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with future motor function decline. RESULTS: For the functional decline group, all T1 values decreased, while fat fraction values increased significantly over 12 months (P<0.05). For the functional stability group, only the fat fraction of the flexors and abductors increased significantly over 12 months (P<0.05). The baseline T1 value was positively correlated with North Star Ambulatory Assessment and negatively correlated with timed functional tests at the 12-month follow-up (P<0.001), while the baseline fat fraction value was negatively correlated with North Star Ambulatory Assessment and positively correlated with timed functional tests at the 12-month follow-up (P<0.001). Multivariate regression showed that increased fat fraction of the abductors was associated with future motor function decline (model 1: odds ratio [OR]=1.104, 95% confidence interval [CI]: 1.026~1.187, P=0.008; model 2: OR=1.085, 95% CI: 1.013~1.161, P=0.019), with an area under the curve of 0.874. CONCLUSION: Fat fraction of the abductors is a powerful predictor of future motor functional decline in DMD patients at 12 months, underscoring the importance of focusing early on this parameter in patients with DMD.
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Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/patologia , Estudos de Coortes , Músculo Esquelético/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , BiomarcadoresRESUMO
OBJECTIVE: Seizure occurs when the balance between excitatory and inhibitory (E/I) inputs to neurons is perturbed, resulting in abnormal electrical activity. This study investigated whether an existing E/I imbalance in neural networks is a useful diagnostic biomarker for Rolandic epilepsy by a resting-state dynamic causal modeling-based support vector machine (rs-DCM-SVM) algorithm. METHODS: This multicenter study enrolled a discovery cohort (76 children with Rolandic epilepsy and 76 normal controls [NCs]) and a replication cohort (59 children with Rolandic epilepsy and 60 NCs). Spatial independent component analysis was used to seven canonical neural networks, and a total of 25 regions of interest were selected from these networks. The rs-DCM-SVM classifier was used for individual classification, consensus feature selection, and feature ranking. RESULTS: The rs-DCM-SVM classifier showed that the E/I imbalance in brain networks is a useful neuroimaging biomarker for Rolandic epilepsy, with an accuracy of 88.2% and 81.5% and an area under curve of .92 and .83 in the discovery and the replication cohorts, respectively. Consensus brain regions with the highest contributions to the classification were located within the epilepsy-related networks, indicating that this classifier was suitable. Consensus functional connection pairs with the highest contributions to the classification were associated with an excitation network loop and an inhibition network loop. The excitation loop mediated the integration of advanced cognitive networks (subcortex, dorsal attention, default mode, executive control, and salience networks), whereas the inhibition loop was involved in the segregation of sensorimotor and language networks. The two loops showed functional segregation. SIGNIFICANCE: Brain E/I imbalance has potential to serve as a biomarker for individual classification in children with Rolandic epilepsy, and might be an important mechanism for causing seizures and cognitive impairment in children with Rolandic epilepsy.
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Epilepsia Rolândica , Biomarcadores , Encéfalo/diagnóstico por imagem , Criança , Eletroencefalografia , Humanos , Imageamento por Ressonância Magnética/métodos , Convulsões , Máquina de Vetores de SuporteRESUMO
In this study, we intended to describe a human case of lumbosacral canal sparganosis in People's Republic of China (China). A 56-year-old man was admitted to Xiangya Hospital Central South University in Changsha, Hunan province, China after having an experience of perianal pain for a week. An enhancing mass, a tumor clinically suggested, was showed at the S1-S2 level of the lumbosacral spine by the examination of magnetic resonance imaging (MRI) with gadolinium contrast. The patient was received the laminectomy from S1 to S2, and an ivory-white living worm was detected in inferior margin of L5. In ELISA-test with cerebrospinal fluid (CSF) and serum samples, anti-sparganum antibodies were detected. He had a ingesting history of undercooked frog meat in his youth. By the present study, a human case of spinal sparganosis invaded in lumbosacral canal at the S1-S2 level was diagnosed in China. Although the surgical removal of larvae is known to be the best way of treatment for sparganosis, we administered the high-dosage of praziquantel, albendazole and dexamethasone to prevent the occurrence of another remain worms in this study.
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Esparganose , Adolescente , Animais , China , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Praziquantel , Esparganose/diagnóstico por imagem , Esparganose/cirurgia , PlerocercoideRESUMO
The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Camundongos , Camundongos Endogâmicos C57BL , SulfatosRESUMO
Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1ß stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.
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Artrite Reumatoide/metabolismo , Endopeptidases/metabolismo , Fibroblastos/citologia , Sinoviócitos/metabolismo , Artrite Reumatoide/imunologia , Células Cultivadas , Endopeptidases/imunologia , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Sinoviócitos/imunologia , Fator 6 Associado a Receptor de TNF/metabolismoRESUMO
Aberrant ROCK activation has been found in patients with several autoimmune diseases, but the role of ROCK in myasthenia gravis (MG) has not yet been clearly investigated. Here, we demonstrated that ROCK activity was significantly higher in peripheral blood mononuclear cells (PBMCs) from MG patients. ROCK inhibitor Fasudil down-regulated the proportions of Th1 and Th17 cells in PBMCs of MG patients in vitro. Intraperitoneal injection of Fasudil ameliorated the severity of experimental autoimmune myasthenia gravis (EAMG) rats and restored the balance of Th1/Th2/Th17/Treg subsets. Furthermore, Fasudil inhibited the proliferation of antigen-specific Th1 and Th17 cells, and inhibited CD4â¯+â¯T cells differentiated into Th1 and Th17 through decreasing phosphorylated Stat1 and Stat3, but promoted Treg cell differentiation through increasing phosphorylated Stat5. We conclude that dysregulated ROCK activity may be involved in the pathogenic immune response of MG and inhibition of ROCK activity might serve as a novel treatment strategy for MG.
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Miastenia Gravis/imunologia , Fator de Transcrição STAT5/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Quinases Associadas a rho/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Células Cultivadas , Modelos Animais de Doenças , Feminino , Homeostase , Humanos , Fosforilação , Ratos , Ratos Endogâmicos Lew , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.
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Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Células Hep G2 , Humanos , Janus Quinases/antagonistas & inibidores , Janus Quinases/metabolismo , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Piridinas/síntese química , Piridinas/química , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/metabolismo , Relação Estrutura-AtividadeRESUMO
An implantable axial blood pump was designed according to the circulation assist requirement of severe heart failure patients of China. The design point was chosen at 3 L/min flow rate with 100 mm Hg pressure rise when the blood pump can provide flow rates of 2-7 L/min. The blood pump with good hemolytic and anti-thrombogenic property at widely operating range was designed by developing a structure that including the spindly rotor impeller structure and the diffuser with splitter blades and cantilevered main blades. Numerical simulation and particle image velocimetry (PIV) experiment were conducted to analyze the hydraulic, flow fields and hemolytic performance of the blood pump. The results showed that the blood pump could provide flow rates of 2-7 L/min with pressure rise of 60.0-151.3 mm Hg when the blood pump rotating from 7 000 to 11 000 r/min. After adding the splitter blades, the separation flow at the suction surface of the diffuser has been reduced efficiently. The cantilever structure changed the blade gap from shroud to hub that reduced the tangential velocity from 6.2 m/s to 4.3-1.1 m/s in blade gap. Moreover, the maximum scalar shear stress of the blood pump was 897.3 Pa, and the averaged scalar shear stress was 37.7 Pa. The hemolysis index of the blood pump was 0.168% calculated with Heuser's hemolysis model. The PIV and simulated results showed the overall agreement of flow field distribution in diffuser region. The blood damage caused by higher shear stress would be reduced by adopting the spindle rotor impeller and diffuser with splitter blades and cantilevered main blades. The blood could flow smoothly through the axial blood pump with satisfactory hydraulics performance and without separation flow.
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Desenho de Equipamento , Insuficiência Cardíaca/terapia , Coração Auxiliar , China , Simulação por Computador , Hemólise , Humanos , Modelos CardiovascularesRESUMO
Recent fMRI studies have demonstrated that resting-state functional connectivity (FC) is of nonstationarity. Temporal variability of FC reflects the dynamic nature of brain activity. Exploring temporal variability of FC offers a new approach to investigate reorganization and integration of brain networks after stroke. Here, we examined longitudinal alterations of FC temporal variability in brain networks after stroke. Nineteen stroke patients underwent resting fMRI scans across the acute stage (within-one-week after stroke), subacute stage (within-two-weeks after stroke), and early chronic stage (3-4 months after stroke). Nineteen age- and sex-matched healthy individuals were enrolled. Compared with the controls, stroke patients exhibited reduced regional temporal variability during the acute stages, which was recovered at the following two stages. Compared with the acute stage, the subacute stage exhibited increased temporal variability in the primary motor, auditory, and visual cortices. Across the three stages, the temporal variability in the ipsilesional precentral gyrus (PreCG) was increased first and then reduced. Increased temporal variability in the ipsilesional PreCG from the acute stage to the subacute stage was correlated with motor recovery from the acute stage to the early chronic stage. Our results demonstrated that temporal variability of brain network might be a potential tool for evaluating and predicting motor recovery after stroke.
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Encéfalo/fisiopatologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Processamento de Sinais Assistido por Computador , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de TempoRESUMO
AIM: The present study aimed to examine the effect of tumor necrosis factor-α (TNF-α) inhibition on bone marrow-derived mesenchymal stem cells (BMSCs) in neurological function recovery after spinal cord injury (SCI) via the Wnt signaling pathway in a rat model. METHODS: The rat model of SCI was established using Allen's method. Seventy-two adult male Sprague Dawley (SD) rats were randomly assigned into 4 groups (18 rats in each group): the sham control group, saline control group, BMSCs group (injection with BMSCs at the injured site) and BMSCs + TNF-α group (injection with BMSCs under TNF-α treatment at the injured site). Immunochemistry was performed to characterize the culture media after TNF-α-induced differentiation. qRT-PCR and Western blotting analyses were performed to detect the mRNA and protein expression of ß-catenin, Wnt3a, GSK-3ß and Axin. The Basso Beattie Bresnahan (BBB) locomotor score, neurological deficit score (NDS), and balance beam test (BBT) score were used to assess neurological functional recovery of SCI rats. RESULTS: In the BMSC group, numerous spherical cell clusters grew in suspension, and the cells were nestin-, NF200- and GFAP-positive. Compared with the sham control and BMSC groups, the ß-catenin and Wnt3a mRNA and protein expression was increased, but the GSK-3ß and Axin mRNA and protein expression was decreased in the BMSCs + TNF-α group. The SCI rats in the BMSCs + TNF-α group exhibited lower BBB scores, and higher NDSs and BBT scores compared to the BMSCs group. CONCLUSION: Our study provides evidence that TNF-α inhibition may weaken the ability of BMSCs in neurological functional recovery after SCI by activating the Wnt signaling pathway.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Traumatismos da Medula Espinal/terapia , Fator de Necrose Tumoral alfa/genética , Animais , Medula Óssea/metabolismo , Diferenciação Celular/genética , Humanos , Ratos , Recuperação de Função Fisiológica/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Via de Sinalização Wnt/genética , beta Catenina/genéticaRESUMO
BACKGROUND: Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. METHODS: Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). RESULTS: Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. CONCLUSION: Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.
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Rim/anormalidades , Rim/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Ureter/diagnóstico por imagem , Urografia/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo , Adulto JovemRESUMO
High-throughput screening, a powerful tool for the discovery of functionally important genes responsible for certain phenotypes, is performed according to loss-of-function or gain-of-function strategies. RNAi technology or knockout approaches have been widely used in high throughput screening due to their advantages of ease use, low cost and so on. However, imcomplete knockdown activity and off-target effect hindered their utility. More recently, CRISPR/Cas9 technology is becoming a robust tool for genome editing in diverse cells or animals, since it could generate a gene mutation in a target-specific manner. In this review, we first summarize the characterization of CRISPR/Cas9 and make comparison with traditional genetic tools, then describe recent achievements of genetic screen in several model organisms using CRISPR/Cas9, finally discuss on its future challenges and opportunities.
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Sistemas CRISPR-Cas/genética , Ensaios de Triagem em Larga Escala , Testes Genéticos , Humanos , Modelos Animais , Mutação , Edição de RNARESUMO
BACKGROUND: Osteoporosis is a systemic skeletal disease with the high incidence, serious complications, financial burden, and heavily decrease in living quality. METHODS: Proliferation of osteoblast was tested by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, alkaline phosphatase (ALP) activity of osteoblasts was tested by ALP REAGENT, Calcium level was determined by a colorimetric assay, mRNA expression of phosphoinositide-3 kinase (PI3K), 3-phosphoinositide-dependent protein kinase 1 (PDK1), Akt, Caspase-3, Caspase-7, Caspase-9, osteocalcin (OCN), Osterix and Runx2 of osteoblasts was tested by RNA preparation and quantitative reverse transcription polymerase chain reaction (RT-PCR), and protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt was measured by Western Blot analysis. RESULTS: In osteoporosis model rats, it found that mRNA expression of PI3K, PDK1 and Akt showed no changes while protein expression of phospho-PI3K, phospho-PDK1 and phospho-Akt in bone tissue was decreased dramatically. To further characterize the molecular mechanisms that regulate osteoporosis, we examined the contribution of the PI3K/Akt cell signaling pathway in cultured osteoblasts. It suggested that, the blockade of PI3K activation by LY294002, a specific inhibitor of the PI3K/Akt signaling pathway in osteoblasts, heavily inhibited cell proliferation, ALP activity, calcium accumulation, and mRNA expression of OCN, Osterix and Runx2. However, mRNA expression of Caspase-3 and Caspase-9 was promoted accordingly. CONCLUSION: The in vivo and in vitro studies indicated that the PI3K/Akt cell signaling pathway is involved in the inhibition of osteoporosis through promoting osteoblast proliferation, differentiation and bone formation.
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Modelos Animais de Doenças , Osteoblastos/metabolismo , Osteoporose/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Apoptose , Western Blotting , Cálcio/metabolismo , Proliferação de Células , Células Cultivadas , Feminino , Osteoblastos/citologia , Osteoporose/etiologia , Osteoporose/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ligante RANK/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIMS: Danon disease is an Xlinked dominant lysosomal glycogen storage disorder characterized by cardiomyopathy, skeletal myopathy, and mental retardation. This study described two Chinese cases of Danon disease in order to broaden the phenotypic and genetic spectrum. METHODS: Clinical data were collected and LAMP2 mutations were analyzed. RESULTS: Patient A had fluctuating limb weakness during 6 months follow-up and was diagnosed with drug-induced myopathy due to anti-hepatitis B therapy with lamivudine. However, the first muscle biopsy with large cytoplasmic vacuoles confused the diagnosis and led to the second biopsy that allowed for the final diagnosis. Patient B had severe cardiac disturbances leading to sudden death. Molecularly, patient A harbored a synonymous mutation adjacent to the exon 6-intron 6 junction; mRNA analysis provided evidence that totally abolished the donor site and caused skipping of exon 6. Patient B harbored a frame-shift deletion mutation in exon 3 (c.396delA) leading to a truncated protein. DISCUSSION: To our knowledge, this is the first report of Danon disease caused by a synonymous exon mutation that affected mRNA splicing, which indicates that a synonymous substitution may not be silent when it is in the exon sequences close to the splice sites. It is also the first description of Danon disease clinically presenting as druginduced myopathy at onset; the pathological changes might be the key point for making a differential diagnosis. *These two authors contributed equally to this work.
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Povo Asiático/genética , Doença de Depósito de Glicogênio Tipo IIb/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Mutação , Sequência de Bases , Western Blotting , Análise Mutacional de DNA , Humanos , Imuno-Histoquímica , Masculino , Linhagem , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
AIM: To investigate the relation between brain ischemia and persistent vegetative state after severe traumatic brain injury. METHODS: The 66 patients with severe brain injury were divided into two groups: The persistent coma group (coma duration ≥10 d) included 51 patients who had an admission Glasgow Coma Scale (GCS) of 5-8 and were unconscious for more than 10 d. There were 15 patients in the control group, their admission GCS was 5-8, and were unconscious for less than 10 d. The brain areas, including frontal, parietal, temporal, occipital lobes and thalamus, were measured by Single Photon Emission Computed Tomography (SPECT). RESULTS: In the first SPECT scan, multiple areas of cerebral ischemia were documented in all patients in both groups, whereas bilateral thalamic ischemia were presented in all patients in the persistent coma group and were absented in the control group. In the second SPECT scan taken during the period of analepsia, with an indication that unilateral thalamic ischemia were persisted in 28 of 41 patients in persistent coma group(28/41,68.29%). CONCLUSION: Persistent coma after severe brain injury is associated with bilateral thalamic ischemia.
Assuntos
Lesões Encefálicas/complicações , Isquemia Encefálica/etiologia , Coma/etiologia , Adolescente , Adulto , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Criança , Pré-Escolar , Coma/diagnóstico , Coma/terapia , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Tomógrafos Computadorizados , Tomografia Computadorizada de Emissão de Fóton Único , Adulto JovemRESUMO
OBJECTIVE: To explore the clinical significance of the protection of superior petrosal vein (SPV) in the microneurosurgery for acoustic neuroma. METHODS: From January 2009 to July 2011, 149 cases of acoustic neuroma microsurgery were observed. The difference in hematoma in surgical area, cerebellar hematoma and cerebellar edema were compared between a SPV without protection group (SPVWP group, n=8) and a SPV protection group (SPVP group, n=141). RESULTS: In the 149 patients with acoustic neuroma, the SPV was reserved in 141 patients. In the SPVWP group (8 patients), hematoma in the surgery area occurred in 4 patients, cerebellar edema in 5, and cerebellar hemorrhage in 3. In the SPVP group (141 patients), hematoma in the surgery area occurred in 40 patients, cerebellar edema in 56, and cerebellar hemorrhage in 12. There was significant difference in the incidence of cerebellar hemorrhage (χ(2)=3.84, P=0.05), no significant difference in the incidence of hematoma in the surgical area (χ(2)=0.646, respectively, P=0.422), and no significant difference in the incidence of cerebellar edema (χ(2)=0.611, P=0.434) between the SPVWP group and the SPVP group. CONCLUSION: In acoustic neuroma surgery, the SPV should be protected, which may reduce the risk of cerebellar hemorrhage.
Assuntos
Ângulo Cerebelopontino/irrigação sanguínea , Doenças dos Nervos Cranianos/cirurgia , Microcirurgia/métodos , Neuroma Acústico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veias/anatomia & histologia , Veias/cirurgia , Adulto JovemRESUMO
BACKGROUND: Primary dedifferentiated chondrosarcoma (DDCS) of the lung is extremely rare and has a poor prognosis, especially in patients with a history of carcinomas and related treatment. Herein, we report a case of primary DDCS of the lung in a patient with a 4-year history of breast cancer and related treatment. CASE SUMMARY: A 49-year-old woman was admitted to our hospital with complaints of headache, dizziness, slurred speech, and dyskinesia in May 2021. Computed tomography (CT) examinations showed multiple nodules in the brain, vertebral body, and both lungs with multiple enlarged lymph nodes in the right hilum and mediastinum, which were considered metastases of breast cancer. No obvious mass was discovered in the right hilum. After several months of related administration, the patient's headache disappeared, and her condition improved. However, new problems of asthma, dyspnea, cough, and restricted activity appeared in late November 2021. Although the CT scan indicated that the lesions in the brain, lung, and vertebral body had shrunk or disappeared, a soft tissue density lesion appeared in her right hilum and blocked the bronchial lumen. To relieve her dyspnea, part of the mass was resected, and a stent was placed via fiberoptic bronchoscopy. Following a complete pathological examination of the tumor, it was confirmed to be a primary DDCS of the lung. The patient then received two rounds of systemic chemotherapy with a regimen of cisplatin + ifosfamide + doxorubicin hydrochloride liposome, palliative radiotherapy for the tumor in her right lung, and four cycles of systemic chemotherapy and targeted therapy with a regimen of temozolomide combined with bevacizumab successively. She was in stable condition after the completion of the systemic chemotherapy and targeted therapy but underwent rapid progression after lung radiotherapy. The CT examinations showed multiple nodules in the brain and in both lungs, and the tumor in the right hilum was increased in size. CONCLUSION: This case revealed a rare primary DDCS of the lung with a medical history of breast cancer, meaning a worse prognosis and making it more difficult to treat.
RESUMO
Under normal circumstances, gastric mucosa only exists within the stomach. However, in certain situations, gastric mucosal tissue may undergo ectopia, commonly occurring in the esophagus and intestine, with rare occurrences within the stomach itself. A comprehensive literature review was performed to understand the distinct characteristics of ectopic gastric mucosa (EGM) in the stomach and investigate a rare incident of this disease, providing an in-depth analysis of the clinical, histopathologic, and differential diagnostic findings. The case was a 47-year-old man with acid reflux, heartburn, abdominal distension, and diarrhea (5-10 times daily) for >10 years. A gastroscope indicated a submucosal protuberance lesion in the gastric body that felt hard with biopsy forceps. A well-defined nodule under the mucosal muscle was revealed microscopically, composed of epithelial elements and no atypia. Immunohistochemical staining demonstrated similar EGM expression patterns compared with normal gastric mucosa. The present case report highlights the importance of accurate EGM diagnosis and understanding.