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Sheng Zhang Yan Wang Jie Xu Bokyung Kim Wenbin Deng Fuzheng Guo 《The Journal of neuroscience》2021,41(2):251
The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury. 相似文献
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目的分析真菌性血流感染的病原菌分布以及耐药特征,为真菌血流感染的早期合理用药提供理论依据。
方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。
结果入组192例真菌血流感染者的血培养样本中共分离192株真菌,其中白色念珠菌检出率为31.77%(61/192),其次热带念珠菌检出率为18.75%(36/192);重症医学科检出率最高为33.85%(65/192)。所有菌株均对两性霉素B敏感,对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%(9/192)、伊曲康唑5.73%(11/192)、氟康唑10.94%(21/192)和伏立康唑11.46%(22/192);除两性霉素B外,2016至2018年真菌对其他抗菌药物的耐药率均逐年上升,其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。
结论真菌血流感染病原菌以念珠菌属为主,对目前抗真菌药物具有较高敏感性,但耐药率逐年上升,加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。 相似文献
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Hanna Lee Mary K. Tan Andrew T. Yan Paul Angaran Paul Dorian Claudia Bucci Jean C. Gregoire Alan D. Bell Martin S. Green Peter L. Gross Allan Skanes Charles R. Kerr L. Brent Mitchell Jafna L. Cox Vidal Essebag Brett Heilbron Krishnan Ramanathan Carl Fournier Shaun G. Goodman 《The Canadian journal of cardiology》2019,35(2):160-168
Background
Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.Methods
We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male).Results
Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians.Conclusions
Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation. 相似文献68.
Stephanie A. Grilo Marina Catallozzi John S. Santelli Hanying Yan Xiaoyu Song Jennifer Heitel Kristen Kaseeska Julie Gorzkowski Alexandra E. Dereix Jonathan D. Klein 《The Journal of adolescent health》2019,64(3):311-318
Purpose
The objective of the study was to define factors associated with adolescent and young adult (AYA) experiences with private time and having discussed confidentiality and the impact of these experiences on improving delivery of clinical preventive services.Methods
In 2016, a nationally representative sample of 1,918 US AYAs (13- to 26-year-olds) was surveyed. Survey questionnaire domains were based on prior research and Fishers' information-motivation-behavior skills conceptual model. Data were weighted to represent US households with AYA and analyzed to identify factors independently associated with ever experiencing private time and discussions of confidentiality with a regular health-care provider (HCP). We examined the association of these experiences on AYA attitudes about health care.Results
Fifty-five percent of female and 49% of male AYA reported ever having had private time with an HCP and 55% of female and 44% of male AYA had spoken to an HCP about confidentiality. Independent predictors of having experienced private time and confidentiality included older age, race, higher household income, gender of the provider, amount of years with the provider, and involvement in risk behaviors. AYA who had experienced private time and confidentiality discussions had more positive attitudes about their providers, were more willing and comfortable discussing sensitive topics, and thought that these discussions should happen at younger ages.Conclusions
Although confidentiality and private time are important to AYA, many are not experiencing these components of care. Providing private time and discussions of confidentiality can improve the delivery of health care for young people by enhancing positive youth attitudes about preventive care. 相似文献69.
肝性脑病是终末期肝硬化的重要并发症,导致病人出现一系列神经及认知功能改变。肝移植术后病人在肝功能恢复的同时其认知功能也可明显改善。MRI可以从脑代谢、结构及功能方面更进一步揭示肝硬化病人移植术后认知及脑改变情况。综述肝移植术后认知改变的研究现状以及最新的多模态MRI技术在术后脑改变中的应用,及其在揭示术后认知恢复及残存损害的神经机制中的价值。 相似文献
70.
目的 分析H型高血压患者的舌面诊图像颜色参数特征,探讨H型高血压患者的舌诊、面诊变化规律。方法 运用上海中医药大学自行研制的Smart TCM-1型中医舌面一体仪,采集高血压患者舌面诊图像,提取特征参数,分析健康对照组、H型高血压组与非H型高血压组患者舌面颜色参数特征。结果 ①在舌色各项参数中,H型高血压组舌尖部R值、B值、V值均显著小于健康对照组(P < 0.01);非H型高血压组舌尖部B值显著小于健康对照组(P < 0.01),S值较健康对照组显著增大(P < 0.05);H型高血压组舌尖部R、V值均明显小于非H型高血压组(P < 0.05)。在舌苔各项参数中,H型高血压组舌中H值、V值均明显小于健康对照组(P < 0.05);非H型高血压组舌中V值、舌右V值均显著小于健康对照组(P < 0.01);H型高血压组舌中H值明显小于非H型高血压组(P < 0.05),右侧舌苔S值明显大于非H型高血压组(P < 0.05)。②H型高血压组面色参数鼻G值、下颌G值、口唇R值、口唇V值均明显小于健康对照组(P < 0.05);非H型高血压组前额H值、目眶H值、脸颊H值、鼻H值、下颌H值、整体H值均明显大于健康对照组(P < 0.05);H型高血压组前额H值、目眶G值、目眶H值、脸颊H值、鼻G值、鼻H值、下颌R值、下颌G值、下颌H值、下颌V值、口唇R值、口唇G值、口唇V值、整体R值、整体G值、整体H值、整体V值均明显小于非H型高血压组(P < 0.05)。结论 H型高血压患者苔色偏黄,以舌中部为主,且舌右侧黄苔积聚较明显;H型高血压患者面色为黄中带红,口唇、下颌部更为晦暗。H型高血压患者的舌、面诊特征参数的变化,与高血压病阳亢湿盛病机相符。 相似文献