Both Xp11 translocation renal cell carcinomas and the corresponding mesenchymal neoplasms are characterized by a variety of gene fusions involving TFE3. It has been known that tumors with different gene fusions may have different clinicopathologic features; however, further in-depth investigations of subtyping Xp11 translocation-associated cancers are needed in order to explore more meaningful clinicopathologic correlations. A total of 22 unusual cases of Xp11 translocation-associated cancers were selected for the current study; 20 cases were further analyzed by RNA sequencing to explore their TFE3 gene fusion partners. RNA sequencing identified 17 of 20 cases (85%) with TFE3-associated gene fusions, including 4 ASPSCR1/ASPL-TFE3, 3 PRCC-TFE3, 3 SFPQ/PSF-TFE3, 1 NONO-TFE3, 4 MED15-TFE3, 1 MATR3-TFE3, and 1 FUBP1-TFE3. The results have been verified by fusion fluorescence in situ hybridization (FISH) assays or reverse transcriptase polymerase chain reaction (RT-PCR). The remaining 2 cases with specific pathologic features highly suggestive of MED15-TFE3 renal cell carcinoma were identified by fusion FISH assay. We provide the detailed morphologic and immunophenotypic description of the MED15-TFE3 renal cell carcinomas, which frequently demonstrate extensively cystic architecture, similar to multilocular cystic renal neoplasm of low malignant potential, and expressed cathepsin K and melanotic biomarker Melan A. This is the first time to correlate the MED15-TFE3 renal cell carcinoma with specific clinicopathologic features. We also report the first case of the corresponding mesenchymal neoplasm with MED15-TFE3 gene fusion. Additional novel TFE3 gene fusion partners, MATR3 and FUBP1, were identified. Cases with ASPSCR1-TFE3, SFPQ-TFE3, PRCC-TFE3, and NONO-TFE3 gene fusion showed a wide variability in morphologic features, including invasive tubulopapillary pattern simulating collecting duct carcinoma, extensive calcification and ossification, and overlapping and high columnar cells with nuclear grooves mimicking tall cell variant of papillary thyroid carcinoma. Furthermore, we respectively evaluated the ability of TFE3 immunohistochemistry, TFE3 FISH, RT-PCR, and RNA sequencing to subclassify Xp11 translocation-associated cancers. In summary, our study expands the list of TFE3 gene fusion partners and the clinicopathologic features of Xp11 translocation-associated cancers, and highlights the importance of subtyping Xp11 translocation-associated cancers combining morphology, immunohistochemistry, and multiple molecular techniques.

Curcumin, the most active component of turmeric, has various beneficial properties, such as antioxidant, anti-inflammatory, and antitumor effects. Previous studies have suggested that curcumin reduces the levels of amyloid and oxidized proteins and prevents memory deficits and thus is beneficial to patients with Alzheimer’s disease (AD). However, the molecular mechanisms underlying curcumin’s effect on cognitive functions are not well-understood. In the present study, we examined the working memory and spatial reference memory in rats that received a ventricular injection of amyloid-β1-42 (Aβ1-42), representing a rodent model of Alzheimer’s disease (AD). The rats treated with Aβ1-42 exhibited obvious cognitive deficits in behavioral tasks. Chronic (seven consecutive days, once per day) but not acute (once a day) curcumin treatments (50, 100, and 200 mg/kg) improved the cognitive functions in a dose-dependent manner. In addition, the beneficial effect of curcumin is accompanied by increased BDNF levels and elevated levels of phosphorylated ERK in the hippocampus. Furthermore, the cognition enhancement effect of curcumin could be mimicked by the overexpression of BDNF in the hippocampus and blocked by either bilateral hippocampal injections with lentiviruses that express BDNF shRNA or a microinjection of ERK inhibitor. These findings suggest that chronic curcumin ameliorates AD-related cognitive deficits and that upregulated BDNF-ERK signaling in the hippocampus may underlie the cognitive improvement produced by curcumin.

P ulse wave velocity (PWV) is a measure of arterial stiffness and can be measured by recording pulse waves on 2 superficial arterial sites and measuring the distance between the 2 arterial sites.1 PWV is usually measured using the applanatation technique between carotid and femoral arteries, 2 between carotid and brachial arteries, 3 or between femoral and tibial or dorsalis arteries. 4 Carotid-femoral PWV is considered as a measure of aortic arterial stiffness and mostly studied for cardiovascular prediction.1 Several studies have demonstrated that carotid-femoral PWV predicts cardiovascular events and mortality in the general population 5,6 and in various patient cohorts. 7,8 Carotid-femoral PWV is, therefore, recommended by several recent hypertension guidelines as a measure of target-organ damage. 9,10 Current technology allows automatic detection of pulse waves using cuffs on the limb arterial sites, such as the brachial and posterior tibial arteries. With the time difference between the pulse waves of these arterial sites and an estimated travel path of the pulse waves according to body height, brachialankle PWV can then be calculated.11 Previous studies have shown that brachial-ankle PWV is closely correlated with carotid-femoral PWV 12 and is also predictive of cardiovascular events and mortality in the general population [13][14][15][16] and in various patient cohorts. [17][18][19][20][21][22][23][24][25] Nonetheless, brachial-ankle PWV measures stiffness of mixed elastic with muscular arteries, 26 instead of the elastic aorta alone, and hence quantitatively differs from carotid-femoral PWV and may have distinct values of cardiovascular prediction. In the present study, we investigated the predictive value of brachial-ankle PWV for mortality in an elderly Chinese population. Methods Study PopulationOur study was conducted in the framework of the Chronic Disease Detection and Management in the Elderly (≥60 years) Program supported by the municipal government of Shanghai. 27,28 In a newly urbanized suburban town, 30 km from the city center, we invited all residents ≥60 years to take part in comprehensive examinations of cardiovascular disease and risk. The Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, approved the study protocol. All subjects gave written informed consent.A total of 4140 subjects (participation rate 90%) were enrolled in the period from 2006 to 2011 and followed up for vital status and cause of death till June 30, 2013. We excluded 101 subjects from the present analysis, because brachial-ankle PWV was not measured (n=63) or because of missing other information (n=38). We further excluded 163 subjects with an ankle-brachial index <0.90 (n=107) or Abstract-Pulse wave velocity (PWV) is a measure of arterial stiffness and predicts cardiovascular events and mortality in the general population and various patient populations. In the present study, we investigated the predictive value of brachial-ankle PWV for mortality in an elderly Chinese population. Ou...