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原发性肝癌(PLC)是临床上常见的消化系统恶性肿瘤之一,90%以上为肝细胞癌(HCC)。大多数原发性肝细胞癌患者存在肝炎基础疾病,肝功能差,局部治疗后易复发,确诊时已到晚期,进展快,预后极差。晚期原发性肝细胞癌系统治疗包括基础肝病治疗、系统化疗、分子靶向治疗、免疫治疗,本文就晚期原发性肝细胞癌的系统化疗、分子靶向治疗、免疫治疗作一综述。 相似文献
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Jules Muhire Hong Lin Zhai Shao Hua Lu Sha Sha Li Bo Yin Jia Ying Mi 《Chemical biology & drug design》2020,95(2):240-247
Non‐structural viral protein 5B (NS5B) is a viral protein in hepatitis C virus. Although various inhibitors against NS5B have been found, the activity prediction of similar untested inhibitors is still highly desirable. In this respect, the Tchebichef moments (TMs) calculated from the images of molecular structures were regarded as the independent variables while the inhibitory activity (pIC50) was the dependent variable, and the predictive model was established by means of stepwise regression. The R‐squared of leave‐one‐out cross‐validation (Q2) for the training set and the R‐squared of prediction () for external independent test set were 0.919 and 0.927, respectively. The obtained model was also evaluated strictly. Compared with the multivariate curve resolution with alternating least squares (MCR‐ALS) and the QSAR approaches derived from the literature, the proposed method is more accurate and reliable. This study not only provides an effective approach to predict the biological activity of RNA replication's inhibitors, but also extends the QSAR modeling technique. 相似文献
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目的探讨SMARCB1(INI1)缺失的鼻腔鼻窦癌临床病理特征及其诊断和鉴别诊断。方法收集2016至2018年复旦大学附属眼耳鼻喉科医院手术切除SMARCB1(INI1)缺失的鼻腔鼻窦癌标本/活检病例6例,观察其临床特点、影像学特征、组织形态、免疫组织化学特征以及预后,并结合文献进行复习。结果5例男性,1例女性;年龄37~75岁(平均约56岁)。1例患者属于T2期,5例患者属于T4期,CT及MRI示鼻腔鼻窦占位伴骨质破坏。镜下观察:肿瘤境界不清,基底样细胞型4例,肿瘤细胞形态较单一,高核质比,细胞质稀少,呈巢状或片状分布于间质中;横纹肌样细胞型2例,肿瘤细胞呈巢状或条索状排列,细胞胞质丰富,嗜酸性,核偏位。免疫组织化学染色示6/6 INI1完全缺失,6/6弥漫强阳性表达广谱细胞角蛋白(CKpan),6/6均不表达S-100蛋白,6/6 EB病毒编码的小RNA(EBER)原位杂交阴性,4/6部分表达p63,1/5部分表达突触素,1/5部分表达p16,Ki-67阳性指数范围30%~70%。5例患者随访1~26个月,其中1例因广泛转移死亡,1例复发,2例淋巴结转移,1例无复发和转移。1例失访。结论SMARCB1(INI1)缺失的鼻腔鼻窦癌恶性程度高,病程进展快,预后差,组织形态主要为基底样细胞型和横纹肌样细胞型,细胞核INI1完全缺失有助于诊断及鉴别诊断。 相似文献
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Zhai Shuting Lin Shuang Lin Zhongjie Xu Junjie Ji Tong Chen Ke Wu Ke Liu Hui Ying Hanning Fei Weiqiang Wang Jin Fu Guoxiang Wang Yifan Hu Xiaotong Cai Xiujun 《Gastric cancer》2020,23(3):483-496
Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome... 相似文献
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Reduced silent information regulator 1 signaling exacerbates myocardial ischemia–reperfusion injury in type 2 diabetic rats and the protective effect of melatonin 下载免费PDF全文
Guolong Zhao Zhenxiao Jin Mengen Zhai Yang Yang Wensheng Chen Jincheng Liu Wei Yi Jian Yang Dinghua Yi Weixun Duan Shiqiang Yu 《Journal of pineal research》2015,59(3):376-390
Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia–reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high‐fat diet‐fed streptozotocin (HFD‐STZ) rat, a well‐known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2α/ATF4‐mediated ER stress. HFD‐STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up‐regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2α/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia–reperfusion injury‐induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion‐induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function. 相似文献
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Cherubism is a rare, nonneoplastic, self-limiting fibro-osseous that occurs in children. Affected children usually appear normal at birth. Lesions are characterized by the replacement of bone with fibrovascular tissue containing many multinucleated giant cells. Most studies have reported cherubism to be familial and with bilateral involvement of the mandibles. The authors describe a nonfamilial case of cherubism, involving both the mandible and the maxilla, in a 4-year-old female child with slowly enlarging, painless, symmetrical swelling of both cheeks.Cherubism is a rare disease that is usually limited to the mandible, but the maxilla may be involved. Computed tomography scan and biopsy are helpful for early diagnosis. 相似文献
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A homogenization-based five-step multi-scale finite element (FsMsFE) simulation framework is developed to describe the time-temperature-dependent viscoelastic behavior of 3D braided four-directional composites. The current analysis was performed via three-scale finite element models, the fiber/matrix (microscopic) representative unit cell (RUC) model, the yarn/matrix (mesoscopic) representative unit cell model, and the macroscopic solid model with homogeneous property. Coupling the time-temperature equivalence principle, multi-phase finite element approach, Laplace transformation and Prony series fitting technology, the character of the stress relaxation behaviors at three scales subject to variation in temperature is investigated, and the equivalent time-dependent thermal expansion coefficients (TTEC), the equivalent time-dependent thermal relaxation modulus (TTRM) under micro-scale and meso-scale were predicted. Furthermore, the impacts of temperature, structural parameters and relaxation time on the time-dependent thermo-viscoelastic properties of 3D braided four-directional composites were studied. 相似文献