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1.
JAMA ; 331(10): 840-849, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38329440

RESUMO

Importance: It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective: To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants: This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023. Interventions: Eligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures: The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results: Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance: Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability. Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2100051729.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Idoso , Método Duplo-Cego , Trombectomia/efeitos adversos , Hemorragias Intracranianas , Metilprednisolona/efeitos adversos
2.
Schizophr Res ; 266: 127-135, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401411

RESUMO

Formal Thought Disorder (FTD) is a defining feature of schizophrenia, which is often assessed through patients' speech. Meanwhile, the written language is less studied. The aim of the present study is to establish and validate a comprehensive clinical screening scale, capturing the full variety of empirical characteristics of writing in patients with schizophrenia. The 16-item Screening Instrument for Schizophrenic Features in Writing (SISFiW) is derived from detailed literature review and a "brainstorming" discussion on 30 samples written by patients with schizophrenia. One hundred and fifty-seven participants (114 patients with an ICD-10 diagnoses of schizophrenia; 43 healthy control subjects) were interviewed and symptoms assessed with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Thought, Language, and Communication (TLC). Article samples written by each participant were rated with the SISFiW. Results demonstrated significant difference of the SISFiW-total between the patient group and healthy controls [(3.61 ± 1.72) vs. (0.49 ± 0.63), t = 16.64, p<0.001]. The inter-rater reliability (weighted kappa = 0.72) and the internal consistency (Cronbach's alpha coefficient = 0.613) were acceptable, but correlations with the criterion (PANSS and TLC) were unremarkable. The ROC analysis indicated a cutoff point at 2 with the maximal sensitivity (93.0 %)/specificity (93.0 %). Discriminant analysis of the SISFiW items yielded 8 classifiers that discriminated between the diagnostic groups at a perfect overall performance (with 90.4 % of original and 88.5 % cross-validated grouped cases classified correctly). This instrument appears to be practicable and reliable, with relatively robust discriminatory power, and may serve as a complementary tool to existing FTD rating scales.


Assuntos
Demência Frontotemporal , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Reprodutibilidade dos Testes , Escalas de Graduação Psiquiátrica , Idioma , Psicometria
3.
Cell Death Discov ; 9(1): 259, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37491360

RESUMO

Cisplatin is an efficient chemotherapeutic agent for various solid tumors, but its usage is restricted by nephrotoxicity. A single dose of cisplatin can cause acute kidney injury (AKI), which is characterized by rapid reduction in kidney function. However, the current therapies, such as hydration, are limited. It is vital to develop novel therapeutic reagents that have both anticancer and renoprotective properties. The objective of this study was to determine whether ammonium tetrathiomolybdate (TM), a copper chelator used to treat cancer and disorders of copper metabolism, may offer protection against cisplatin-induced AKI. In this study, we demonstrated that TM treatment had antioxidative effects and mitigated cisplatin-induced AKI both in vivo and in vitro. Mechanically, TM inhibited NRF2 ubiquitination, which activated the NRF2 pathway in HK-2 cells and promoted the expression of target genes. It should be noted that the protective effect conferred by TM against cisplatin was compromised by the knockdown of the NRF2 gene. Furthermore, TM selectively activated the NRF2 pathways in the liver and kidney. The current study provided evidence for additional clinical applications of TM by showing that it activates NRF2 and has a favorable therapeutic impact on cisplatin-induced AKI.

4.
Front Oncol ; 13: 1191614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427120

RESUMO

Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future.

5.
N Engl J Med ; 388(22): 2025-2036, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37256974

RESUMO

BACKGROUND: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied. METHODS: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours. Patients were assigned to receive intravenous tirofiban (plus oral placebo) or oral aspirin (100 mg per day, plus intravenous placebo) for 2 days; all patients then received oral aspirin until day 90. The primary efficacy end point was an excellent outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. Secondary end points included functional independence at 90 days and a quality-of-life score. The primary safety end points were death and symptomatic intracranial hemorrhage. RESULTS: A total of 606 patients were assigned to the tirofiban group and 571 to the aspirin group. Most patients had small infarctions that were presumed to be atherosclerotic. The percentage of patients with a score of 0 or 1 on the modified Rankin scale at 90 days was 29.1% with tirofiban and 22.2% with aspirin (adjusted risk ratio, 1.26; 95% confidence interval, 1.04 to 1.53, P = 0.02). Results for secondary end points were generally not consistent with the results of the primary analysis. Mortality was similar in the two groups. The incidence of symptomatic intracranial hemorrhage was 1.0% in the tirofiban group and 0% in the aspirin group. CONCLUSIONS: In this trial involving heterogeneous groups of patients with stroke of recent onset or progression of stroke symptoms and nonoccluded large and medium-sized cerebral vessels, intravenous tirofiban was associated with a greater likelihood of an excellent outcome than low-dose aspirin. Incidences of intracranial hemorrhages were low but slightly higher with tirofiban. (Funded by the National Natural Science Foundation of China; RESCUE BT2 Chinese Clinical Trial Registry number, ChiCTR2000029502.).


Assuntos
Fibrinolíticos , AVC Isquêmico , Tirofibana , Humanos , Aspirina/efeitos adversos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Tirofibana/efeitos adversos , Tirofibana/uso terapêutico , Resultado do Tratamento , Doenças Arteriais Cerebrais/tratamento farmacológico , Doenças Arteriais Cerebrais/etiologia
6.
Biomolecules ; 13(3)2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36979414

RESUMO

The proteolytic active sites of the 26S proteasome are sequestered within the catalytic chamber of its 20S core particle (CP). Access to this chamber is through a narrow channel defined by the seven outer α subunits. In the resting state, the N-termini of neighboring α subunits form a gate blocking access to the channel. The attachment of the activators or regulatory particles rearranges the blocking α subunit N-termini facilitating the entry of substrates. By truncating or mutating each of the participating α N-termini, we report that whereas only a few N-termini are important for maintaining the closed gate, all seven N-termini participate in the open gate. Specifically, the open state is stabilized by a hydrogen bond between an invariant tyrosine (Y) in each subunit with a conserved aspartate (D) in its counterclockwise neighbor. The lone exception is the α1-α2 pair leaving a gap in the ring circumference. The third residue (X) of this YD(X) motif aligns with the open channel. Phenylalanine at this position in the α2 subunit comes in direct contact with the translocating substrate. Consequently, deletion of the α2 N-terminal tail attenuates proteolysis despite the appearance of an open gate state. In summary, the interlacing N-terminal YD(X) motifs regulate both the gating and translocation of the substrate.


Assuntos
Complexo de Endopeptidases do Proteassoma , Complexo de Endopeptidases do Proteassoma/metabolismo , Modelos Moleculares , Proteólise
7.
J Neurointerv Surg ; 15(8): 808-813, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35985839

RESUMO

BACKGROUND: Locked-in syndrome (LiS) is a rare and devastating condition in patients with acute basilar artery occlusion. However, the benefits of endovascular treatment (EVT) for LiS remain unclear. OBJECTIVE: To assess the outcomes associated with EVT and identify the factors associated with outcomes of LiS. METHODS: We used the data of the Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry (BASILAR) from 47 tertiary stroke centers in China. The included patients had LiS and received EVT or standard medical treatment (SMT) alone. The primary outcome was improvement in the modified Rankin Scale (mRS) score at 90 days. RESULTS: Among the 120 patients with LiS, 92 (76.7%) received EVT and 28 (23.3%) received SMT. Compared with SMT, EVT was associated with improved mRS score (common OR (cOR)=2.68 (95% CI 1.16 to 6.20); p=0.02) and decreased mortality (aOR=0.35 (95% CI 0.13 to 0.90); p=0.03). Moreover, the benefit of EVT for LiS was sustained for at least 1 year (p=0.008). Higher baseline posterior circulation Alberta Stroke Prognosis Early CT Score (pc-ASPECTS, aOR=2.04 (95% CI 1.34 to 3.10); p<0.001) and absence of pneumonia (aOR=0.26 (95% CI 0.08 to 0.90); p=0.03) were significantly associated with favorable functional outcome at 90 days in patients who received EVT, while lower pc-ASPECTS (aOR=0.52 (95% CI 0.36 to 0.76); p<0.001) was associated with increased 90-day mortality. CONCLUSIONS: This study found that EVT was associated with favorable functional outcomes and decreased mortality among patients with LiS. Baseline pc-ASPECTS and pneumonia were independent predictors of outcomes.


Assuntos
Arteriopatias Oclusivas , Procedimentos Endovasculares , Síndrome do Encarceramento , Acidente Vascular Cerebral , Humanos , Trombectomia/efeitos adversos , Síndrome do Encarceramento/etiologia , Resultado do Tratamento , Acidente Vascular Cerebral/terapia , Artéria Basilar , Arteriopatias Oclusivas/etiologia , Procedimentos Endovasculares/efeitos adversos
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(10): 1324-1331, 2022 Oct 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36411683

RESUMO

OBJECTIVES: The liver X receptors (LXRs) are members of the nuclear hormone receptor superfamily, and LXR-ß is an important receptor for cholesterol content in brain cells. LXR-ß/retinoic X receptor (RXR-α)/ATP binding cassette transporter A1 (ABCA1) cholesterol transmembrane transport system is closely related to the occurrence and development of Alzheimer's disease (AD). LXR agonist TO901317 can affect the accumulation of ß- amyloid protein in the brain tissue of APP/PS1 double transgenic AD mice. However, the molecular mechanism is not clarified in detail. This study aims to evaluate the effects of LXR agonist TO901317 on the cognitive function of AD mice fed with high cholesterol diet, and to explore its possible mechanism from the perspective of cholesterol metabolism. METHODS: Twenty four male 6-month-old APP/PS1 double transgenic AD mice were randomly divided into 4 groups, 6 mice in each group: a control group (fed with normal diet), a cholesterol rich diet (CRD) group, a TO901317 group (fed with CRD combined with TO901317), and a GSK2033 group (fed with CRD combined with TO901317 and LXR antagonist GSK2033). The mice were fed with pellet feed made of high cholesterol feed, mixed with lard, egg yolk powder, and cod liver oil twice a day. TO901317 and GSK2033 were dissolved and diluted to a final concentration at 0.03%. The drugs were given to the mice daily through gastric tube according to their body weight. Meanwhile, the mice in the drug group were fed with high cholesterol diet . After feeding for 3 months, Morris water maze was used to observe the changes of spatial exploration and memory ability of AD mice in each group. The contents of TC, LDL, and HDL in serum of mice in each group were detected by cholesterol enzyme colorimetry, and the differences among the groups were compared. The expression of Aß42 in the brain of AD mice was detected by ELISA. Western blotting was used to detect the protein levels of LXR-ß, RXR-α, ABCA1, and Caveolin-1 in the brain of each group. RESULTS: Morris water maze results showed that the times, distance and the duration of mice crossing the platform in the CRD group were significantly decreased compared with the control group (all P<0.05), while these three figures in TO901317 group were significantly increased compared with the CRD group (all P<0.05). Compared with the TO901317 group, there was a decrease of these figures in the GSK2033 group (all P<0.05). The serum TC and LDL levels in the CRD group were significantly higher than those in the control group, while HDL levels were significantly lower (all P<0.001). The figures of the TC and LDL contents level in the TO901317 group were lower than those in the CRD group, while HDL levels were higher (all P<0.001). Compared with TO901317 group, the contents of the TC and LDL in GSK2033 group were significantly increased, while HDL content was significantly decreased (all P<0.001). ELISA results showed that the production of Aß42 peptides in the brain of CRD group was the highest while the content in the TO901317 group was significantly decreased (P<0.001), which was the lowest among the groups. The figure in the control group was close to the GSK2033 group. Western blotting results showed that the protein levels of LXR-ß, RXR-α, and ABCA1 in the CRD group were significantly decreased compared with the control group, but the protein level of Caveolin-1 was increased (all P<0.01). After TO901317 treatment, the protein levels of LXR-ß, RXR-α and ABCA1 were significantly increased, while the protein level of Caveolin-1 was decreased partially (all P<0.001). In the GSK2033 group, the effect of TO901317 on AD mice was partially reversed by GSK2033. Compared to TO901317 group, the protein levels of LXR-ß, RXR-α, and ABCA1 showed a decrease trend, while the protein level of Caveolin-1 showed an increase state (all P<0.05). CONCLUSIONS: High cholesterol diet leads to severer spatial exploration, learning and memory impairment in transgenic AD mice, while the LXR agonist TO901317 attenuates this effect. The mechanism may be that TO901317 promotes cholesterol efflux by activating LXR-ß/RXR-α/ABCA1 transmembrane transport system, reduces the expression of Caveolin-1, improves the composition of lipid raft, and ultimately reduces the production of Aß42 in the brain.


Assuntos
Doença de Alzheimer , Masculino , Animais , Camundongos , Receptores X do Fígado/genética , Receptores X do Fígado/agonistas , Receptores X do Fígado/metabolismo , Camundongos Transgênicos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Caveolina 1/metabolismo , Hidrocarbonetos Fluorados/farmacologia , Cognição , Peptídeos beta-Amiloides/metabolismo , Colesterol
9.
Cancers (Basel) ; 14(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36428735

RESUMO

Neuroblastoma (NB), which is considered to be caused by the differentiation failure of neural crest cells, is the most common extracranial malignant solid tumor in children. The degree of tumor differentiation in patients with NB is closely correlated with the survival rate. To explore the potential targets that mediate NB cell differentiation, we analyzed four microarray datasets from GEO, and the overlapping down- or upregulated DEGs were displayed using Venn diagrams. SOX4 was one of the overlapping upregulated DEGs and was confirmed by RT-qPCR and Western blot in ATRA-treated NGP, SY5Y, and BE2 cells. To clarify whether SOX4 was the target gene regulating NB cell differentiation, the correlation between the expression of SOX4 and the survival of clinical patients was analyzed via the R2 database, SOX4 overexpression plasmids and siRNAs were generated to change the expression of SOX4, RT-qPCR and Western blot were performed to detect SOX4 expression, cell confluence or cell survival was detected by IncuCyte Zoom or CCK8 assay, immunocytochemistry staining was performed to detect cells' neurites, and a cell cycle analysis was implemented using Flow cytometry after PI staining. The results showed that the survival probabilities were positively correlated with SOX4 expression, in which overexpressing SOX4 inhibited NB cell proliferation, elongated the cells' neurite, and blocked the cell cycle in G1 phase, and that knockdown of the expression of SOX4 partially reversed the ATRA-induced inhibition of NB cell proliferation, the elongation of the cells' neurites, and the blocking of the cell cycle in the G1 phase. These indicate that SOX4 may be a target to induce NB cell differentiation.

10.
J Phys Chem Lett ; 13(43): 10207-10215, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36287143

RESUMO

The dispersity of metal particles over oxide surfaces is generally critical for the applications of the metal/oxide hybridized systems. In this work, we have experimentally investigated the hydration effect of preadsorbed water species over the Cu and Pd particles deposited on the ZnO(10-10) surface. Using scanning tunneling microscopy (STM), we clearly saw that both Cu and Pd grow as three-dimensional particles on the clean ZnO(10-10) surface but disperse into single atoms and few-atom clusters on the water-covered surfaces. Moreover, X-ray photoelectron spectroscopy (XPS) measurements revealed that Cu is readily oxidized by interacting with the molecular water while Pd tends to bind the surface hydroxyls and keep neutral status. Our work has demonstrated the effective role of the surface water in tuning the morphologies as well as electronic states of the supported metals, which may bring new insights to a number of important surface processes with water in presence.

12.
Mol Cell Biochem ; 476(10): 3601-3612, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34024029

RESUMO

Neuroblastoma (NB) is the most common malignant extra cranial solid tumors in children. It has been well established that retinoic acid (RA) inhibits proliferation of neuroblastoma (NB) by blocking cells at G1 phase of the cell cycle. Clinically, RA has been successfully used to treat NB patients. However, the precise mechanism underlying the potent action of RA-treated NB is not fully explored. In this work, we carried out a gene expression profiling by RNA sequencing on all-trans retinoic acid (ATRA)-treated NB cells. Cancer-related pathway enrichment and subsequent protein-protein interaction (PPI) network analysis identified fibronectin 1 (FN1) as one of the central molecules in the network, which was significantly upregulated during ATRA treatment. In addition, we found that although downregulation of FN1 had no significant effects on either cell proliferation or cell cycle distributions in the presence or absence of ATRA, it increased cell migration and invasion in NB cells and partially blocked ATRA-induced inhibition of cell migration and invasion in SY5Y NB cells. Consistent with this finding, FN1 expression levels in NB patients positively correlate with their overall survivals. Taken together, our data suggest that FN1 is a potential target for effective ATRA treatment on NB patients, likely by facilitating ATRA-induced inhibition of cell migration and invasion.


Assuntos
Movimento Celular/efeitos dos fármacos , Fibronectinas/metabolismo , Proteínas de Neoplasias/metabolismo , Neuroblastoma/metabolismo , Tretinoína/farmacologia , Linhagem Celular Tumoral , Movimento Celular/genética , Fibronectinas/genética , Humanos , Invasividade Neoplásica/genética , Proteínas de Neoplasias/genética , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética
13.
Phys Chem Chem Phys ; 23(21): 12449-12455, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34037035

RESUMO

The development of environmentally friendly, simple process and low cost synthesis methods for preparing graphene nanosheets (GNs) has attracted global interest. In this work, a simple and efficient method to synthesize GNs deriving from coal-tar pitch has been proposed from both experimental and theoretical point of views. The XRD, TEM and Raman results demonstrate that precursor Al4C3 could provide a growth environment for the final product of GNs. Innovatively, we have unraveled the microscopic origin for the decomposition of Al4C3 based on density functional theory calculations. It is highlighted that the surface energies and the analysis of elastic constants indicate the fact that the chemical etching process in Al4C3 can happen, which is similar to the exfoliation of well-known transition metal carbides MXenes. Furthermore, different bond breaking mechanisms have been found in Al4C3 at applied tensile and shear strains from the electron localization functions and stress-strain results. Our study not only offers an efficient method to synthesize GNs, but also to unravel the microscopic mechanism of fabrication by theoretical calculations.

14.
Front Neurol ; 12: 774443, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34975733

RESUMO

Background and Purpose: It is unknown the benefit of endovascular therapy (EVT) for progressive stroke in patients with basilar artery occlusion (BAO). The aim of this study was to compare the efficacy and safety of EVT with standard medical therapy (SMT) in a population of BAO patients with progressive stroke. Methods: The EVT for Acute Basilar Artery Occlusion Study (BASILAR) is a national prospective registry of consecutive patients with acute BAO within 24 h of symptom onset. According to the applied therapy, all patients were divided into SMT and EVT groups. Subsequently, the EVT group was divided into early (≤6 h) and late groups (>6 h) according to the time window. The efficacy outcome was favorable functional outcomes (modified Rankin Scale score ≤ 3) at 90 days. The safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage (sICH) after EVT. Results: The EVT cohort presented more frequently with a favorable functional outcome (adjusted odds ratio, 5.49; 95% confidence interval, 2.06-14.61, p = 0.01) and with a decreased mortality (adjusted odds ratio, 0.3; 95% confidence interval, 0.17-0.54, p < 0.001). What's more, EVT still safe (P = 0.584, P = 0.492, respectively) and effective (P = 0.05) in patients with progressive stroke when the treatment time window exceeds 6 h. Conclusions: EVT was more effective and safer than SMT for progressive stroke in patients with BAO. Besides, EVT remains safe and effective in patients with progressive stroke when the treatment time window exceeds 6 h. Predictors of desirable outcome in progressive stroke patients undergoing EVT included lower baseline NIHSS score, higher baseline pc-ASPECTs, successful recanalization and shorter puncture to recanalization time.

15.
RSC Adv ; 12(2): 998-1004, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-35425138

RESUMO

Constructing van der Waals (vdW) heterostructures has been proved to be an excellent strategy to design or modulate the physical and chemical properties of 2D materials. Here, we investigated the electronic structures and solar cell performances of the g-C3N4/WTe2 heterostructure via first-principles calculations. It is highlighted that the g-C3N4/WTe2 heterostructure presents a type-II band edge alignment with a band gap of 1.24 eV and a corresponding visible light absorption coefficient of ∼106 cm-1 scale. Interestingly, the band gap of the g-C3N4/WTe2 heterostructure could increase to 1.44 eV by enlarging the vdW gap to harvest more visible light energy. It is worth noting that the decreased band alignment difference resulting from tuning the vdW gap, leads to a promotion of the power conversion efficiency up to 17.68%. This work may provide theoretical insights into g-C3N4/WTe2 heterostructure-based next-generation solar cells, as well as a guide for tuning properties of vdW heterostructures.

16.
Life Sci ; 256: 117820, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32512012

RESUMO

Neuroblastoma (NB) is one of the most common malignant tumors in children. Chemotherapy resistance is one of the significant challenges in the treatment of high-risk NB patients, and it is necessary to search for new valid targets for NB treatment. This study aims to explore the possible role of PIF1 in NB by using bioinformatic analysis and downregulation of PIF1 with specific siRNA. Kyoto genome encyclopedia and R language based gene ontology was used to analyze the differentially expressed genes (DEGs) (including PIF1) when MYCN expression was silenced in NB cells. Analysis based on the R2 database showed a lower expression of PIF1 correlated with good prognosis in NB patients. Downregulation of MYCN expression by transfecting MYCN siRNA (#1, #2) into NB cells decreased the PIF1 expression at both mRNA and protein levels, while upregulation of MYCN expression by transfecting MYCN overexpressed plasmid increased the PIF1 expression. We further found that downregulation of PIF1 expression by transfecting PIF1 siRNA (#1, #2) into NB cells, increased the number of apoptotic cells, inhibited the cell survival, decreased the ability of cell migration and induced a cell cycle arrest at G1 phase. These data indicated that PIF1, as a potential new target of MYCN, maybe a novel target for NB treatment.


Assuntos
Apoptose/genética , Movimento Celular/genética , DNA Helicases/genética , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Biologia Computacional , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neuroblastoma/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Regulação para Cima
17.
Phys Chem Chem Phys ; 21(39): 21898-21907, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31552974

RESUMO

Monolayers of III-VI group two-dimensional (2D) materials MX (M = Ga and In and X = S, Se, and Te) have attracted global interest for potential applications in electronic and photoelectric devices due to their attractive physical and chemical characteristics. However, a comprehensive understanding of the distinguished carrier mobility in MX monolayers is of great importance and not yet clear. Herein, using a Boltzmann transport equation (BTE) solver and first principles calculations, we have precisely revealed that the intrinsic mobility in MX monolayers is significantly limited by phonon scattering. Note that the longitudinal acoustic phonon mode and optic phonon modes and were found predominantly coupled with electrons, which strongly restrained the intrinsic mobility in the MX monolayers. Interestingly, apart from a moderate band gap, the GaSe and GaTe monolayers exhibit high electron mobility exceeding 103 cm2 V-1 s-1 and may serve as outstanding electron transport channels. We believe that our findings will shed light on the design and applications of MX monolayers and 2D materials in nanoscale electronic and photoelectric devices.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(9): 734-736, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30210025

RESUMO

OBJECTIVE: To study the value of transesophageal atrial pacing (TEAP) in neonates with tachyarrhythmia. METHODS: The clinical data of 26 neonates with tachyarrhythmia who underwent TEAP electrophysiological examination or cardioversion were collected. RESULTS: Of the 26 neonates, 15(58%) were diagnosed with atrioventricular reentrant tachycardia, 3(12%) were diagnosed with sinus tachycardia, 3(12%) were diagnosed with ventricular tachycardia, 2(8%) were diagnosed with fast/slow atrioventricular nodal reentrant tachycardia, 2(8%) were diagnosed with atrial tachycardia, and 1(4%) was diagnosed with sinus tachycardia with ventricular preexcitation. Overdrive suppression was performed for 22 neonates, among whom 18 achieved successful cardioversion, and 2 with atrial tachycardia and 2 with ventricular tachycardia failed to restore sinus rhythm. CONCLUSIONS: TEAP is helpful to the diagnosis of tachyarrhythmia in neonates and can bring about a high rate of cardioversion success.


Assuntos
Taquicardia por Reentrada no Nó Atrioventricular , Taquicardia Ventricular , Estimulação Cardíaca Artificial , Cardioversão Elétrica , Eletrocardiografia , Humanos , Recém-Nascido , Taquicardia por Reentrada no Nó Atrioventricular/terapia , Taquicardia Ventricular/terapia
19.
Shanghai Arch Psychiatry ; 27(6): 374-7, 2015 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-27199530

RESUMO

An increase in the concentration of eosinophils in blood may lead to endocarditis, myocarditis, and pericarditis. When the absolute eosinophil count increases beyond 1.5 x 10(9)/L, myocardial damage and even death can occur. This case report describes a 47-year-old male with an alcohol-induced psychotic disorder who developed eosinophilia 4 weeks after starting treatment with quetiapine 50-200 mg/d. His maximum recorded absolute eosinophil count was 7.63 x 10(9)/L (normal range < 0.5 x 10(9)/L), but the level returned to normal over a 4-week period after stopping quetiapine and no myocardial damage was observed. This patient's dramatic eosinophilia did not have any associated clinical symptoms; it was only identified as part of a routine blood test a few weeks after starting quetiapine. This is a reminder that all clinicians who treat patients with antipsychotic medications must be vigilant about the occurrence of such rare but life-threatening adverse events.

20.
Clin Vaccine Immunol ; 19(3): 418-28, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22258709

RESUMO

Successful vaccination against smallpox with conventional vaccinia virus is usually determined by the development of a vesicular skin lesion at the site of vaccinia inoculation, called a "take." Although previous vaccination is known to be associated with attenuation of the take, the immunology that underlies a no-take in vaccinia-naïve individuals is not well understood. We hypothesized that antibody profiling of individuals before and after receiving vaccinia virus would reveal differences between takes and no-takes that may help better explain the phenomenon. Using vaccinia virus proteome microarrays and recombinant protein enzyme-linked immunosorbent assays (ELISAs), we first examined the antibody response in vaccinia-naïve individuals that failed to take after receiving different doses of the replication-competent DryVax and Aventis Pasteur (APSV) smallpox vaccines. Most that received diluted vaccine failed to respond, although four no-takes receiving diluted vaccine and four receiving undiluted vaccine mounted an antibody response. Interestingly, their antibody profiles were not significantly different from those of controls that did show a take. However, we did find elevated antibody titers in no-takes prior to receiving DryVax that were significantly different from those of takes. Although the sample size studied was small, we conclude the failure to take in responders correlates with preexisting immunity of unknown etiology that may attenuate the skin reaction in a way similar to previous smallpox vaccination.


Assuntos
Anticorpos Antivirais/sangue , Pele/patologia , Vacina Antivariólica/imunologia , Vírus Vaccinia/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Análise Serial de Proteínas , Proteínas Virais/imunologia
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