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Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
Subject(s)
Animals , Mice , Disease Models, Animal , Hydrocephalus/genetics , Mice, Knockout , Neurons , beta Catenin/geneticsABSTRACT
Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.
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<p><b>OBJECTIVE</b>To review the research methods of mass casualty incident (MCI) systematically and introduce the concept and characteristics of complexity science and artificial system, computational experiments and parallel execution (ACP) method.</p><p><b>DATA SOURCES</b>We searched PubMed, Web of Knowledge, China Wanfang and China Biology Medicine (CBM) databases for relevant studies. Searches were performed without year or language restrictions and used the combinations of the following key words: "mass casualty incident", "MCI", "research method", "complexity science", "ACP", "approach", "science", "model", "system" and "response".</p><p><b>STUDY SELECTION</b>Articles were searched using the above keywords and only those involving the research methods of mass casualty incident (MCI) were enrolled.</p><p><b>RESULTS</b>Research methods of MCI have increased markedly over the past few decades. For now, dominating research methods of MCI are theory-based approach, empirical approach, evidence-based science, mathematical modeling and computer simulation, simulation experiment, experimental methods, scenario approach and complexity science.</p><p><b>CONCLUSIONS</b>This article provides an overview of the development of research methodology for MCI. The progresses of routine research approaches and complexity science are briefly presented in this paper. Furthermore, the authors conclude that the reductionism underlying the exact science is not suitable for MCI complex systems. And the only feasible alternative is complexity science. Finally, this summary is followed by a review that ACP method combining artificial systems, computational experiments and parallel execution provides a new idea to address researches for complex MCI.</p>
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Humans , Mass Casualty IncidentsABSTRACT
Objective To evalhate the protective effect of oral raloxifene on lung function after acute lung injury (ALI) in rats. Methods Thirty male adult Sprague-Dawley rats were used and divided into three groups: LPS raloxifene hydrochloric acid. group before secondary impact ( Group A, n = 10 ), LPS raloxifene hydrochloric acid group after secondary impact ( Group B, n = 10) and control group ( n = 10). All the rats were injected intraperitoneally with 5 mg/kg LPS. Raloxifene (30 mg/kg) was orally administered one hour before LPS injection and 14 hours after LPS injection in Groups A and B. The con-trol group remained free. All the animals were anesthetized by intraperitoneal injection of pentobarbital so-dium at 40 mg/kg and the femoral artery was cannulated 16 hours after LPS injection to measure the mean arterial pressure (MAP). All the rats received a direct intratracheal injection of hydrochloric acid ( pH = 1.2, 0.5 ml/kg). Before injection of hydrochloric acid and at 0. 5,1.5 and 4 hours after injection of hy-drochloric acid, the blood gas was measured. Fifteen rats ( five from each group) underwent a micro posi-tron emission tomography ( [18F] FDG microPET) scan of the thorax four hours after hydrochloric acid in-stillation. Then, the lung tissue was collected for histopathological examination. Results The Group B showed better pulmonary gas exchange and more stable MAP compared to the control group. The [18F] fluorodeoxyglueose uptake and histological lung injury score were 9. 01 ± 1.58 and 12.6 ± 0.97 respec-tively in Group B, which were higher than 4. 67 ± 1.33 and 9. 01 ± 1.58 respectively in control group (P < 0. 01 ). Conclusions Raloxifene exerts significant protective effect on lung function after ALI. [18F] FDG microPET is a useful method to evaluate the inflammatory reaction during ALI.
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Objective To identify the potential risk factors affecting mortality rate of ALl in severe trauma population. Method It was a retrospective cohort study treating trauma as a single cause for emergency depart-ment (ED)) and emergency intensive care unit (EICU) admissions. Eighteen potential risk factors affecting the mortality of ALI were examined by univariate and multivariate logistic analyses in these severe trauma patients. Re-sults There were 343 severe trauma patients with post-traumatic ALI admitted to ED and EICU the Second Affili-ated Hospital Medical College,Zhejiang University,during the study period. The five risk factors that affected the mortality with unadjusted odd ratios (ORs) and 95% confidence intervals (CIs) were (1) APACHE Ⅱ score, (2)duration of trauma, (3) age, (4) aspiration of gastric contents, and (5) DIC. Specific risk factors also affected different patients subpepulations at different degrees. Conclusions Factors of APACHE Ⅱ score and aspiration of gastric contents that can predict the mortality of ALl may exist in the early stage of trauma. Duration of trauma and DIC that greatly affect the short- and long-term development of ALI deserve special attention. Elderly patients (aged beyond 65 years) are the independent risk factor for the secondary sepsis and deterioration of pulmonary function. Patients with these risk factors need aggressive supportive care as early as possible in order to prevent fur-ther aggravation.
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Objective To investigate cerebral functional remodeling of the rat with severe acute carbon monoxide poisoning transplanted with neural stem-like cells derived from bone marrow mesenchymal stem cells (MS-NSCs) . Method Forty Sprague-Dawley rats weighing 200 ~ 250 g were divided randomly into 4 groups: the normal control group, the poisoning control group, the bone marrow mesenchymal stem cells(BMSCs) transplantation group and the MS-NSCs transplantation group. BMSCs were harvested from whole bone marrow in vitro, then were differentiated into MS-NSCs under certain growth factors cocktail,and were followed by BrdU labelling.Twenty-four hours after poisoning, the seed cells were infused into brain via left internal carotid and the functional remodeling of cerebrum was assessed by neurological severity score(NSS) and Morris water maze(MWM) tests. Results There was no significant differences in NSS test between groups after transplantation. However, the differences in MWM test were very significant between 5 weeks after transplantation ( P < 0.01). Conclusions Transplantation of MS-NSCs may improved cerebral function of rats after severe acute CO poisoning. Moreover, the cultured and idfferentiated MS-NSCs induced in vitro preliminarily is potentially more efficient than directly transplanted BMSCs without culture and differentiation.
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Objective To evaluate potential clinical risk factors for the development of early-onset myocardial damage following multiple trauma (MT), and to determine whether early-onset myocardial damage was caused by the combined effects of thoracic and systemic injury factors in MT patients.Methods A total of 231 patients with MT over the last 3 years were retrospectively reviewed. With myocardial damage being a dependent variable and other twenty factors being independent variables, univariate and multivariate logistic regressions were applied to investigate the risk factors for early-onset myocardial damage and to identify the association of thoracic and systemic risk factors with early-onset myocardial damage.Results Multivariable logistic regressions showed that acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) score ≥10, injury severity score (ISS) ≥ 25, shock index ≥ 2,coexisting chest trauma, abbreviated injury scale (AIS) of chest≥3, and hypoxia time ≥ 0.5 h were risk factors. The risk of earlyonset myocardial damage following MT obviously increased when thoracic and systemic injury risk factors were coexisting.Conclusion Our results indicated that thoracic injury combined with systemic injury increased the overall risk of early-onset myocardial damage following MT. Prospective validation of these findings in other clinical settings is warranted.
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The three links theory" refers to the three key links in an emergency medical services system, viz. pre-hospital first-aid system, hospital emergency care system, and the ICU system. The construction of an emergency medical services system in China ought to be guided by the three links theory so as to set up a practical and highly efficient emergency medical services system, an instantly operating monitoring system, a smooth and real-time information system, a rational and long-lasting system of laws and contingency plans, and a system for cultivating universalists. The goal is to build an emergency green passage in the hospital.
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The paper gives an account of the new ideas in trauma care and the transition of emergency care of trauma from the traditional model to the modern model,viz.the transition of emergency care of trauma by the emergency department from a paradigm of general practice to a paradigm of specialized care;the transition of trauma physicians training from a paradigm of general practitioners to a paradigm of specialists;and the transition of the flow of emergency care of trauma from a paradigm of "links" to a paradigm of "whole course".Based on the practice of the emergency department of the hospital the authors work with in setting up a quick clinical response mechanism of emergency care of trauma,a mechanism of priority to emergency care of trauma,a hospital-wide linking and coordinating mechanism of emergency care of trauma,a standardized management mechanism of wards for emergency care of trauma,and an operational mechanism of the team of emergency care of trauma,the paper discusses building an integrated model of emergency care of trauma on the basis of the "three links theory" by the emergency department.