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21.
Chloride channel 3 (CIC-3) has been suggested to be implicated in the carcinogenesis though; it still remains ill understood in hepatocarcinoma, especially in terms of clinicopathological meaning of its expression. Given this, herein, to understand the clinicopathological significance of CIC-3 expression in hepatocarcinoma, Immunohistochemistry was performed to examine the level of CIC-3, followed by statistical analysis of the correlation between expression versus clinicopathological variables, including gender, age, TNM classifications, tumor size, lymph node metastasis and overall prognosis. It was shown that positive staining of CIC-3 can be present in both hepatocarcinoma and its paired normal controls; and that CIC-3 was significantly over-expressed in hepatcarcioma on the whole relative to paired normal controls. Moreover, up-regulation of CIC-3 markedly correlated with tumor size and overall prognosis, suggesting that CIC-3 expression could predict both tumor size and overall prognosis in hepatocarcinoma.  相似文献   
22.
Throughout the developing GC response, B cell survival and fate choices made at the single cell level are dependent on signals received largely through interactions with other cells, often with cognate T cells. The type of signals that a given B cell can encounter is dictated by its location within tissue microarchitecture. The focus of this review is on the initiation and evolution of the GC response at the earliest time points. Here, we review the key factors influencing the progression of GC B cell differentiation that are both stage and context dependent. Finally, we describe the coevolution of niches within and surrounding the GC that influence the outcome of the GC response.  相似文献   
23.
Liu  Yixin  Wei  Wei  Wang  Yang  Wan  Chunyou  Bai  Yingyu  Sun  Xuguo  Ma  Jun  Zheng  Fang 《Inflammation research》2019,68(7):597-611
Inflammation Research - The present study was undertaken to validate whether TNF-α and calreticulin (CRT) serve as dual signaling to activate nucleotide-binding oligomerization domain-,...  相似文献   
24.
25.
The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.  相似文献   
26.
Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.  相似文献   
27.

Objectives

Treatment landscape in prostate cancer has changed dramatically with the emergence of new medicines in the past few years. The traditional survival partition model (SPM) cannot accurately predict long-term clinical outcomes because it is limited by its ability to capture the key consequences associated with this changing treatment paradigm. The objective of this study was to introduce and validate a discrete-event simulation (DES) model for prostate cancer.

Methods

A DES model was developed to simulate overall survival (OS) and other clinical outcomes based on patient characteristics, treatment received, and disease progression history. We tested and validated this model with clinical trial data from the abiraterone acetate phase III trial (COU-AA-302). The model was constructed with interim data (55% death) and validated with the final data (96% death). Predicted OS values were also compared with those from the SPM.

Results

The DES model’s predicted time to chemotherapy and OS are highly consistent with the final observed data. The model accurately predicts the OS hazard ratio from the final data cut (predicted: 0.74; 95% confidence interval [CI] 0.64–0.85 and final actual: 0.74; 95% CI 0.6–0.88). The log-rank test to compare the observed and predicted OS curves indicated no statistically significant difference between observed and predicted curves. However, the predictions from the SPM based on interim data deviated significantly from the final data.

Conclusions

Our study showed that a DES model with properly developed risk equations presents considerable improvements to the more traditional SPM in flexibility and predictive accuracy of long-term outcomes.  相似文献   
28.
宋见喜  任婷  王贺  牟莹莹  冯丽娟  孙新  佟海滨 《中草药》2017,48(24):5125-5129
目的优选高山红景天多糖(RSP)的最佳硫酸化修饰条件,提高RSP的抗氧化活性。方法利用氯磺酸-吡啶法对RSP进行了硫酸化修饰,并通过单因素实验确定了硫酸化反应的最佳工艺条件;应用红外光谱(IR)和扫描电子显微镜(SEM)对RSP和硫酸化高山红景天多糖(S-RSP)的理化性质进行了分析;通过测定RSP和S-RSP对1,1-二苯基-2-三硝基苯肼(DPPH)自由基的清除能力,考察了S-RSP的取代度(DS)与多糖抗氧化活性之间的关系。结果当氯磺酸与吡啶的体积比为1∶4、反应时间为2 h、反应温度为60℃时,制得的S-RSP的含硫量最大值为18.83%,取代度最大值为2.38。RSP经硫酸化修饰后,增强了其抗氧化活性,S-RSP的DS与DPPH自由基清除能力存在一定的正比例关系。结论氯磺酸与吡啶的体积比影响S-RSP的DS大小;RSP经硫酸化修饰后通过改变多糖的极性而增加了其抗氧化能力。  相似文献   
29.
目的:研究银杏二萜内酯葡胺注射液在人尿液中的主要代谢产物及其代谢途径。方法:3名受试者静脉滴注银杏二萜内酯葡胺注射液后收集0~6 h的尿样,分别按酸化和不酸化样品处理后,以液相色谱-串联质谱法(LC-MS/MS)对样品进行分析。采用ACE C_(18)-AR色谱柱(4.6 mm×150 mm,3μm),酸性HPLC条件流动相Ⅰ为乙腈-0.4%甲酸铵水溶液(p H3.2)梯度洗脱,中性HPLC条件流动相Ⅱ为乙腈-水梯度洗脱,流速0.7 m L·min~(-1)。通过比较空白尿样和给药后尿样的总离子流和提取离子流色谱图以及各个色谱峰的保留时间、准分子离子和二级碎片离子,分析银杏内酯A(GA),银杏内酯B(GB)和银杏内酯K(GK)在人体内可能的代谢产物。结果:除原型药外,共鉴定了12个代谢产物,其中GA相关的代谢产物有6个,包括5个Ⅰ相和1个Ⅱ相代谢产物;GB相关的有4个,包括1个Ⅰ相和3个Ⅱ相代谢产物;GK相关的有2个,包括1个Ⅰ相和1个Ⅱ相代谢产物。结论:GA在人体内主要的代谢途径为羟基化和内酯环水解,并可进一步共价结合成硫酸酯;GB主要的代谢途径为羟基化和内酯环水解,并可进一步共价结合成硫酸酯、葡萄糖醛酸苷或谷胱甘肽结合物;GK在人体内主要的代谢途径为甲基化葡萄糖醛酸结合反应。  相似文献   
30.
《医古文》课程的传统教学模式存在较大问题,难以达到良好的教学效果。为了改进教学方法,提升教学质量,现以建构主义和形成性教学评价为理论基础,举例采用两种趣味互动教学方式,培养学生对传统文化的兴趣,夯实学生的基础知识,提高学生的古文应用能力。证明趣味互动教学法符合当今学生的认知规律,具有独到的优势,并值得推广。  相似文献   
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