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61.
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
62.
Fur-Hsing Wen Jen-Shi Chen Wen-Chi Chou Wen-Cheng Chang Wen Chi Shen Chia-Hsun Hsieh Siew Tzuh Tang 《Journal of pain and symptom management》2019,57(1):64-72
Context
Family caregivers constitute a critical component of the end-of-life care system with considerable cost to themselves. However, the joint association of terminally ill cancer patients' symptom distress and functional impairment with caregivers' subjective caregiving burden, quality of life (QOL), and depressive symptoms remains unknown.Objectives/Methods
We used multivariate hierarchical linear modeling to simultaneously evaluate associations between five distinct patterns of conjoint symptom distress and functional impairment (symptom-functional states) and subjective caregiving burden, QOL, and depressive symptoms in a convenience sample of 215 family caregiver–patient dyads. Data were collected every 2 to 4 weeks over patients' last 6 months.Results
Caregivers of patients in the worst symptom-functional states (States 3–5) reported worse subjective caregiving burden and depressive symptoms than those in the best two states, but the three outcomes did not differ between caregivers of patients in State 3 and States 4–5. Caregivers of patients in State 5 endured worse subjective caregiving burden and QOL than those in State 4. Caregivers of patients in State 4 suffered worse subjective caregiving burden and depressive symptoms but comparable QOL to those in State 2.Conclusion
Patients' five distinct, conjoint symptom-functional states were significantly and differentially associated with their caregivers' worse subjective caregiving burden, QOL, and depressive symptoms while caring for patients over their last 6 months. 相似文献63.
Yuan-Zhang Tang Bai-Shan Wu Li-Qiang Yang Jian-Ning Yue Liang-Liang He Na Li Jia-Xiang Ni 《Medicine》2015,94(45)
To evaluate the efficacy of computed tomography (CT) guided single radiofrequency thermocoagualtion (RFT) in 1137 patients with idiopathic trigeminal neuralgia after a follow-up period of 11 years, specially focused on duration of pain relief in different branches of trigeminal nerve, side effect, and complications.Retrospective study of patients with idiopathic trigeminal neuralgia treated with a single CT guided RFT procedure between January 2002 and December 2013.The mean follow-up time was 46.14 ± 30.91 months. Immediate postprocedure pain relief was 98.4%. V2 division obtained the best pain relief rate: 91%, 89%, 80%, 72%, 60%, and 54% at 1, 3, 5, 7, 9, and 11 years, respectively. No statistical difference pairwise comparison was in other groups. The complications included masseter muscle weakness, corneitis, diplopia, ptosis, hearing loss, limited mouth opening, and low pressure headache. Masticatory weakness mostly occurred in patients with V3 branch involvement, while Corneitis and Diplopia all in patients with V1 branch involvement. No mortalities observed during or after RFT.All different branches division of trigeminal neuralgia achieved comparable satisfactory curative effect; V2 obtained the best excellent pain relief, after RFT procedure. Facial numbness is inevitable after RFT, which patients who have pain in all 3 trigeminal divisions and patients who desire no facial numbness should be cautious. Masticatory weakness is mainly related with V3 injured, while Corneitis and Diplopia in patients with V1 injured by RFT. 相似文献
64.
目的探讨关节镜下使用TightRope治疗后交叉韧带(PCL)撕脱骨折的技术应用和临床疗效。方法 12例膝关节PCL撕脱骨折患者在关节镜下使用TightRope固定PCL撕脱骨块。术后1周开始在支具保护下被动活动膝关节,术后10个月评估膝关节功能恢复情况。结果 12例患者均获随访,时间10~14个月,平均12.6个月,骨折均Ⅰ期愈合。1例屈膝受限15°,无伸膝受限;2例后抽屉试验(+)。Lysholm膝关节功能评分术前(45.6±6.3)分,术后10个月(87.8±4.8)分,差异有统计学意义(P 0.05)。结论关节镜下使用TightRope治疗PCL撕脱骨折固定可靠,操作相对简单,疗效满意。 相似文献
65.
66.
吴洁 《南京中医药大学学报》2019,35(4):376-378
回顾《内经》相关理论,指出痈脓病机关键在于气血凝滞、经络阻塞、脏腑失和,可分期论治。总结《金匮要略》治疗痈脓的方法,认为痈脓应尽早治疗,防邪深入;并根据证情辨证使用清热解毒,活血消散;排除脓毒,泄浊于外等治法。对现代临床仍具实用价值。 相似文献
67.
痘病毒是自然界普遍存在的DNA病毒,能够高效表达外源基因,诱导较强的细胞免疫和体液免疫,受到基因治疗学者的广泛关注。痘病毒发生同源重组的概率较低,所以有效地筛选和纯化痘病毒十分重要。目前常用的筛选重组痘病毒方法有基于CRISPR进行筛选;根据报告基因GFP、LacZ、GPT等进行筛选;利用TK-和Brdu结合荧光进行筛选;利用药物抗性基因与荧光或显色基因融合,即可在药物筛选的同时观察荧光或显色基因表达情况。本文旨在对目前常用的痘病毒的筛选纯化方法进行综述。 相似文献
68.
目的 探讨中性粒细胞与淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定,并依此分NLR<2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素,最佳临界值为2.64。NLR<2.64组术后中位DFS为39.10月,中位OS为52.30月;NLR≥2.64组术后中位DFS为27.35月,中位OS为37.35月。2组术后DFS和OS比较,差异具有统计学意义(P<0.05)。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素,具有重复性强、非侵袭性、方便实用等特性,可用于预测三阴性乳腺癌临床预后。 相似文献
69.
70.