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ABSTRACT BACKGROUND: For critically ill patients, physicians tend to administer sufficient or even excessive oxygen to maintain oxygen saturation at a high level. However, the credibility of the evidence for this practice is unclear. OBJECTIVE: To determine the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated intensive care unit (ICU) patients. DESIGN AND SETTING: Systematic review of the literature and meta-analysis conducted at Jiangxi Provincial People's Hospital, Affiliated to Nanchang University, Nanchang, China. METHODS: We systematically searched electronic databases such as PubMed and Embase for relevant articles and performed meta-analyses on the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated ICU patients. RESULTS: A total of 1802 patients from five studies were included. There were equal numbers of patients in the conservative and liberal groups (n = 910 in each group). There was no significant difference between the conservative and liberal groups with regard to 28-day mortality (risk ratio, RR = 0.88; 95% confidence interval, CI = 0.59-1.32; P = 0.55; I2 = 63%). Ninety-day mortality, infection rates, ICU length of stay, mechanical ventilation-free days up to day 28 and vasopressor-free days up to day 28 were comparable between the two strategies. CONCLUSIONS: It is not necessary to use liberal oxygen therapy strategies to pursue a higher level of peripheral oxygen saturation for mechanically ventilated ICU patients. Conservative oxygen therapy was not associated with any statistically significant reduction in mortality.
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Humanos , Oxigênio , Respiração Artificial , Oxigenoterapia , Prognóstico , Estado Terminal/terapia , Unidades de Terapia Intensiva , Tempo de InternaçãoRESUMO
BACKGROUND: For critically ill patients, physicians tend to administer sufficient or even excessive oxygen to maintain oxygen saturation at a high level. However, the credibility of the evidence for this practice is unclear. OBJECTIVE: To determine the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated intensive care unit (ICU) patients. DESIGN AND SETTING: Systematic review of the literature and meta-analysis conducted at Jiangxi Provincial People's Hospital, Affiliated to Nanchang University, Nanchang, China. METHODS: We systematically searched electronic databases such as PubMed and Embase for relevant articles and performed meta-analyses on the effects of different oxygen therapy strategies on the outcomes of mechanically ventilated ICU patients. RESULTS: A total of 1802 patients from five studies were included. There were equal numbers of patients in the conservative and liberal groups (n = 910 in each group). There was no significant difference between the conservative and liberal groups with regard to 28-day mortality (risk ratio, RR = 0.88; 95% confidence interval, CI = 0.59-1.32; P = 0.55; I2 = 63%). Ninety-day mortality, infection rates, ICU length of stay, mechanical ventilation-free days up to day 28 and vasopressor-free days up to day 28 were comparable between the two strategies. CONCLUSIONS: It is not necessary to use liberal oxygen therapy strategies to pursue a higher level of peripheral oxygen saturation for mechanically ventilated ICU patients. Conservative oxygen therapy was not associated with any statistically significant reduction in mortality.
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Oxigênio , Respiração Artificial , Estado Terminal/terapia , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Oxigenoterapia , PrognósticoRESUMO
Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.
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Polietilenoglicóis/efeitos adversos , Dissolução , Métodos , Polímeros/análise , Preparações Farmacêuticas/análise , Água , Secagem por AtomizaçãoRESUMO
Mechanisms coupling the atypical PKC (aPKC) kinase activity to its subcellular localization are essential for cell polarization. Unlike other members of the PKC family, aPKC has no well-defined plasma membrane (PM) or calcium binding domains, leading to the assumption that its subcellular localization relies exclusively on protein-protein interactions. Here we show that in both Drosophila and mammalian cells, the pseudosubstrate region (PSr) of aPKC acts as a polybasic domain capable of targeting aPKC to the PM via electrostatic binding to PM PI4P and PI(4,5)P2. However, physical interaction between aPKC and Par-6 is required for the PM-targeting of aPKC, likely by allosterically exposing the PSr to bind PM. Binding of Par-6 also inhibits aPKC kinase activity, and such inhibition can be relieved through Par-6 interaction with apical polarity protein Crumbs. Our data suggest a potential mechanism in which allosteric regulation of polybasic PSr by Par-6 couples the control of both aPKC subcellular localization and spatial activation of its kinase activity.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Membrana Celular/enzimologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/enzimologia , Proteínas de Membrana/metabolismo , Proteína Quinase C/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Alostérica , Animais , Animais Geneticamente Modificados , Membrana Celular/ultraestrutura , Polaridade Celular/genética , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Embrião não Mamífero , Células Epiteliais/enzimologia , Células Epiteliais/ultraestrutura , Regulação da Expressão Gênica , Genes Reporter , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Larva/citologia , Larva/enzimologia , Proteínas de Membrana/química , Proteínas de Membrana/genética , Fosfatidilinositol 4,5-Difosfato/química , Fosfatidilinositol 4,5-Difosfato/metabolismo , Fosfatos de Fosfatidilinositol/química , Fosfatos de Fosfatidilinositol/metabolismo , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteína Quinase C/química , Proteína Quinase C/genética , Transdução de Sinais , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Quasiclassical trajectory calculations and vibrational-state-selected beam-surface measurements of CH4 chemisorption on Ir(111) reveal a nonthermal, hot-molecule mechanism for C-H bond activation. Low-energy vibrationally excited molecules become trapped in the physisorption well and react before vibrational and translational energies accommodate the surface. The reaction probability is strongly surface-temperature-dependent and arises from the pivotal role of Ir atom thermal motion. In reactive trajectories, the mean outward Ir atom displacement largely exceeds that of the transition-state geometry obtained through a full geometry optimization. The study also highlights a new way for (temporary) surface defects to impact high-temperature heterogeneous catalytic reactivity. Instead of reactants diffusing to and competing for geometrically localized lower barrier sites, transient, thermally activated surface atom displacements deliver low-barrier surface reaction geometries to the physisorbed reactants.
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STUDY DESIGN: A radiographic analysis of the anatomy of the C1 lateral mass using computed tomography (CT) scans and Mimics software. OBJECTIVE: To define the anatomy of the C1 lateral mass and make recommendations for optimal entry point and trajectory for anterior C1 lateral mass screws. SUMMARY OF BACKGROUND DATA: Although various posterior insertion angles and entry points for screw insertion have been proposed for posterior C1 lateral mass screws, no large series have been performed to assess the ideal entry point and optimal trajectory for anterior C1 lateral mass screw placement. MATERIALS AND METHODS: The C1 lateral mass was evaluated using CT scans and a 3-dimensional imaging application (Mimics software). Measuring the space available for the anterior C1 lateral mass screw (SAS) at different camber angles from 0 to 30 degrees (5-degree intervals) was performed to identify the ideal camber angle of insertion. Measuring the range of sagittal angles was performed to calculate the ideal sagittal angle. Other measurements involving the height of the C1 lateral mass were also made. RESULTS: The optimal screw entry point was found to be located on the anterior surface of the atlas 12.88 mm (±1.10 mm) lateral to the center of the anterior tubercle. This optimal entry point was found to be 6.81 mm (±0.59 mm) superior to the anterior edge of the atlas inferior articulating process. The mean ideal camber angle was 20.92 degrees laterally and the mean ideal sagittal angle was 5.80 degrees downward. CONCLUSIONS: These measurements define the optimal entry point and trajectory for anterior C1 lateral mass screws and facilitate anterior C1 lateral mass screw placement. A thorough understanding of the local anatomy may decrease the risk of injury to the spinal cord, vertebral artery, and internal carotid artery. Delineating the anatomy in each case with preoperative 3D CT evaluation is recommended.
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Parafusos Ósseos , Vértebras Cervicais/cirurgia , Adolescente , Adulto , Fenômenos Biomecânicos , Vértebras Cervicais/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
UNLABELLED: Introduction and Aim. TGF-ß signalling is involved in pathogenesis and progress of hepatocellular carcinoma (HCC). This bioinformatics study consequently aims to determine the underlying molecular mechanism of TGF- ß activation in HCC cells. MATERIAL AND METHODS: Dataset GSE10393 was downloaded from Gene Expression Omnibus, including 2 Huh-7 (HCC cell line) samples treated by TGF- ß (100 pmol/L, 48 h) and 2 untreated samples. Differentially expressed genes (DEGs) were screened using Limma package (false discovery rate < 0.05 and |log2 fold change| > 1.5), and then enrichment analyses of function, pathway, and disease were performed. In addition, protein-protein interaction (PPI) network was constructed based on the PPI data from multiple databases including INACT, MINT, BioGRID, UniProt, BIND, BindingDB, and SPIKE databases. Transcription factor (TF)-DEG pairs (Bonferroni adjusted p-value < 0.01) from ChEA database and DEG-DEG pairs were used to construct TF-DEG regulatory network. Furthermore, TF-pathway-DEG complex network was constructed by integrating DEG-DEG pairs, TF-DEG pairs, and DEG-pathway pairs. RESULTS: Totally, 209 DEGs and 30 TFs were identified. The DEGs were significantly enriched in adhesion-related functions. PPI network indicted hub genes such as CUL4B and NEDD4. According to the TF-DEG regulatory network, the two hub genes were targeted by SMAD2, SMAD3, and HNF4A. Besides, the 11 pathways in TF-pathway-DEG network were mainly enriched by UGT1A family and CYP3A7, which were predicted to be regulated by SMAD2, SMAD3, SOX2, TP63, and HNF4A. CONCLUSIONS: TGF- ß might influence biological processes of HCC cells via SMAD2/SMAD3-NEDD4, HNF4A-CUL4B/NEDD4, SOX2/TP63/HNF4A-CYP3A7, and SMAD2/SMAD3/SOX2/TP63/HNF4A-UGT1As regulatory pathways.
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Carcinoma Hepatocelular/genética , Proteínas Culina/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Glucuronosiltransferase/genética , Neoplasias Hepáticas/genética , Fator de Crescimento Transformador beta/metabolismo , Ubiquitina-Proteína Ligases/genética , Carcinoma Hepatocelular/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Proteínas Culina/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Bases de Dados Genéticas , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Perfilação da Expressão Gênica , Glucuronosiltransferase/metabolismo , Fator 4 Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Ubiquitina-Proteína Ligases Nedd4 , Mapas de Interação de Proteínas , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Transdução de Sinais/genética , Proteína Smad2/genética , Proteína Smad2/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
STUDY DESIGN: A retrospective case series describing teardrop fracture of the axis. OBJECT: The purpose of the study was to clarify the clinical features, the mechanism of injury, and the potential instability of extension teardrop fractures of the axis, so as to emphasize the importance of recognizing this injury as a separate entity. SUMMARY OF BACKGROUND DATA: Teardrop fractures of the axis are rare spinal fractures, comprising only a small percentage of all injuries of the cervical spine. The stability of this fracture pattern has been a matter of debate leading to controversy regarding treatment strategies and the need for stabilization. METHODS: We retrospectively reviewed data collected from 16 patients to document the mechanism of injury, neurological deficit, treatment and clinical outcome, and imaging findings. RESULTS: Extension teardrop fractures accounted for approximately 8.9% of the upper cervical spinal injuries and 12.7% of axis fractures at the authors' institution over the same period. Six patients (4 males and 2 females) underwent surgery (4 by an anterior approach, 2 by a posterior approach). Ten cases underwent Halo-vest immobilization for a period between 6 and 12 weeks. At final follow-up, 14 cases achieved excellent results, whereas 2 patients complained of mild residual neck pain. Maximum cranial-caudal dimensions of the fragments were between 5 and 24 mm (average, 12.9 mm), and the transverse dimensions were between 5 and 22 mm (average, 11.1 mm). Fragment displacement ranged from 1 to 9 mm (average, 3.5 mm), whereas fragment rotation ranged from 10 to 52 degrees (average, 24.4 degrees) in the sagittal plane. CONCLUSIONS: Most patients with an extension teardrop fracture of the axis can be treated conservatively. On the basis of this case series, the authors suggest that large fragment size, displacement or angulation, intervertebral disk injury, neurologic deficit, or signs of instability are reasonable indications for surgical treatment.
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Vértebra Cervical Áxis/lesões , Fraturas da Coluna Vertebral/terapia , Adulto , Idoso , Vértebra Cervical Áxis/diagnóstico por imagem , Feminino , Fixação Interna de Fraturas , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Medição da Dor , Radiografia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/patologia , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Recently, the rs1042713 G > A and rs1042714 C > G polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were shown to be related to atherosclerosis diseases. Therefore, we performed a systemic meta-analysis to determine whether the two functional polymorphisms are related to the risk of myocardial infarction (MI) and coronary artery disease (CAD). We identified published studies that are relevant to our topic of interest. Seven case-control studies, with a total of 6,843 subjects, were incorporated into the current meta-analysis. Our analysis showed a higher frequency of rs1042713 G > A variant in patients with MI or CAD compared to healthy controls. A similar result was also obtained with the rs1042714 C > G variant under both the allele and dominant models. Ethnicity-stratified subgroup analysis suggested that the rs1042714 C > G variant correlated with an increased risk of the two diseases in both Asians and Caucasians, while rs1042713 G > A only contributes to the risk of two diseases in Asians. In the disease type-stratified subgroups, the frequencies of both the rs1042713 G > A and rs1042714 C > G variants were higher in the cases than in the controls in both the MI and CAD subgroups. Collectively, our data contribute towards understanding the correlation between the rs1042713 G > A and rs1042714 C > G polymorphisms in ADRB2 and the susceptibility to MI and CAD.
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STUDY DESIGN: Anatomic study of the C1 lateral mass using fine-cut computed tomographic scans and Mimics software. OBJECTIVE: To investigate the optimal entry point, medial angles, and effective length for safe fixation using posterior C1 lateral mass screws. SUMMARY OF BACKGROUND DATA: Placing posterior C1 lateral mass screws is technically demanding, and a misplaced screw can result in injury to the vertebral artery, spinal cord, or internal carotid artery. Although various insertion angles have been proposed for posterior C1 lateral mass screw, no clear consensus has been reached on the ideal medial angle of the C1 lateral mass. METHODS: The C1 lateral masses were evaluated using computed tomographic scans and Mimics software in 70 patients. The effective width and effective screw length of posterior C1 lateral mass screws were measured at different medial angulations relative to the midline sagittal plane. The height (H) for screw entry point on the posterior surface of C1 lateral mass and the distance (D) between screw entry point and the intersection of the midline sagittal plane and the posterior arch of the atlas were also measured. RESULTS: The mean height (H) for screw entry on the posterior surface of the lateral mass was 4.25 mm, the mean distance (D) between screw entry point and the intersection of the midsagittal plane and the posterior arch of the atlas was 27.62 mm. The optimal medial angle was 20.86° with a corresponding effective width of 10.56 mm and effective screw length of 21.87 mm. CONCLUSION: This study helps to define the specific anatomy related to C1 posterior lateral mass screw placement in an effort to facilitate instrumentation. However, variation is seen in lateral mass anatomy, and this study must be combined with customized surgical planning that includes advanced imaging for safe and effective instrumentation. LEVEL OF EVIDENCE: 1.