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《Molecular therapy》2022,30(8):2856-2867
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  相似文献   
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《Diagnostic Histopathology》2022,28(11):493-500
After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.  相似文献   
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The Poisson-Nernst-Planck (PNP) system is a widely accepted model for simulation of ionic channels. In this paper, we design, analyze, and numerically validate a second order unconditional positivity-preserving scheme for solving a reduced PNP system, which can well approximate the three dimensional ion channel problem. Positivity of numerical solutions is proven to hold true independent of the size of time steps and the choice of the Poisson solver. The scheme is easy to implement without resorting to any iteration method. Several numerical examples further confirm the positivity-preserving property, and demonstrate the accuracy, efficiency, and robustness of the proposed scheme, as well as the fast approach to steady states.  相似文献   
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Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.  相似文献   
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目的观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法采用电点燃刺激法建立小鼠癫痫模型, 观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响, 并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果与对照组比较, 正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12, P < 0.05)、减少大发作概率(53.6% vs 96.5%, P < 0.01) 和缩短后放电持续时间[(16.22 ± 1.69) s vs (30.29 ± 1.12) s, P < 0.01], 而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16, P < 0.05)、减少大发作概率(66.7%, P < 0.01);但对海马后放电持续时间及大发作持续时间无影响(均 P>0.05)。此外, 电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用( P < 0.05或 P < 0.01), 而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。 结论低频率电刺激抗癫痫作用受波形参数的影响, 其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。  相似文献   
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Objective

To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure—specifically through childhood neighborhoods, college student bodies, and friend groups—on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency.

Data Source

Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study.

Study Design

We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time.

Principal Findings

In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency.

Conclusions

Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships.  相似文献   
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目的:建立鼠巨细胞病毒(MCMV)感染C57BL/6小鼠急性肝炎模型并对其感染特点进行分析及鉴定。方法:将24 只C57BL/6小鼠随机分为阴性对照组(n =12)及病毒感染组(n =12),病毒感染组腹腔注射1.0×106 PFU(200 μL)MCMV悬液,阴性对照组注射等体积小鼠胚胎成纤维细胞(MEF)悬液。于感染后第3天和第7天取外周血分离血清检测谷丙转氨酶(ALT)及谷草转氨酶(AST)。同时进行肝组织病毒分离、组织病理学及MCMV IE和M55基因、细胞因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)的检测。结果:病毒感染组肝组织匀浆病毒分离均为阳性,肝炎发生率为100%。在感染后第3天即发生肝炎病理改变,病毒感染组血清ALT及AST较阴性对照组明显升高(P <0.01);病毒感染组肝脏HE染色第3天可见局灶性炎性细胞浸润及肝脏点灶状坏死,持续至第7天,Ishak评分较阴性对照组明显升高(P <0.01);在感染后第3天病毒感染组肝组织内可检测到MCMV IE及M55基因,且在感染后第7天仍可测得IE基因;感染后第3天及第7天病毒感染组炎性细胞因子IL-6、TNF-α及IL-1β mRNA表达水平明显升高(P <0.05)。 结论:成功建立MCMV感染C57BL/6小鼠急性动物肝炎模型,其感染表现主要集中在急性感染前期。  相似文献   
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