Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in ...NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-β downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-β. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.
Amodiaquine is a 4-aminoquinoline antimalarial similar to chloroquine that is used extensively for the treatment and prevention of malaria. Data on the cardiovascular effects of amodiaquine are ...scarce, although transient effects on cardiac electrophysiology (electrocardiographic QT interval prolongation and sinus bradycardia) have been observed. We conducted an individual patient data meta-analysis to characterise the cardiovascular effects of amodiaquine and thereby support development of risk minimisation measures to improve the safety of this important antimalarial. Studies of amodiaquine for the treatment or prevention of malaria were identified from a systematic review. Heart rates and QT intervals with study-specific heart rate correction (QTcS) were compared within studies and individual patient data pooled for multivariable linear mixed effects regression. While caution is advised in the use of amodiaquine in patients aged greater than or equal to12 years with concomitant use of heart rate-reducing medications, serious cardiac conduction disorders, or risk factors for torsade de pointes, there have been no serious cardiovascular events reported after amodiaquine in widespread use over 7 decades. Amodiaquine and structurally related antimalarials in the World Health Organization (WHO)-recommended dose regimens alone or in ACTs are safe for the treatment and prevention of malaria.
In plastically deformed coarse-grained metallic materials, recovery annealing largely decreases their strength because of the annihilation of the stored dislocations. In contrast, the subsequent ...grain growth only slightly decreases their strength. We have found an exactly opposite change in the strength of our annealed nanocrystalline iron- and nickel-based alloys prepared by a severe plastic deformation method – mechanical alloying. In the recovery stage, the microhardness is almost constant and even slightly increases just before the grains start to grow because of the segregation of solutes in the grain boundary. Our experiment results suggest that the dislocations – mainly taking the form of dislocation dipoles – stored in the grain interiors of our mechanically alloyed nanocrystalline alloys do not influence the microhardness. At the grain growth stage, microhardness decreases as the grains grow. In addition, the microhardness of furnace-cooled nanocrystalline alloys is higher than that of air-cooled nanocrystalline alloys, further supporting that the grain boundary segregation influences the microhardness of nanocrystalline alloys. Our experimental results suggest that it is the grain size and the grain boundary structure, rather than the dislocations stored in the grain interiors, that determine the strength of the deformed and annealed nanocrystalline alloys.
The microstructure and texture evolution of a metastable Ti–5Al–3V–3Mo–2Cr–2Zr–1Nb–1Fe alloy during bar-rolling and after various thermal treatments was investigated by high-energy synchrotron ...diffraction and electron backscatter diffraction. Bar-rolling is applied in the (α+β)-phase field in order to achieve a bi-modal (duplex) microstructure. The effect of dynamic recrystallized and recovered zones on texture of Ti5321was analyzed separately, as well as the texture of primary α-precipitates and secondary α-lamellae. The texture of the recovered zones is characterized by a cube component ({001} ) plus α- and γ-fibre with dominant {100} , {112} , {111} components, while the texture of the recrystallized zones is a strong cube texture. After aging or recrystallization plus aging, this texture component remains, while it disappears after solution treatment. The primary α-precipitates have their c-axes perpendicular to the rolling direction and do not follow the Burgers orientation relationship. This texture characteristics remains after various thermal heat treatments. Secondary α-lamellae obey the Burgers orientation relationship. Moreover, a variant selection of secondary α-lamellae occurs. The mechanism of texture formation of the β-phase and the precipitation behavior of the α-phase is discussed. The hardness increase can be attributed to size, shape and volume fraction of the α-precipitates. Different combinations of primary α- and secondary α-precipitates make an increase in hardness of about 11%.
•Recovery and recrystallization during bar-rolling affect the texture of the β-phase.•α-phase obeys the Burgers orientation relationships unless it is codeformed with β.•Hardness can be tuned via precipitation during different heat treatments.
Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) ...hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases.
713 subjects (328 males and 385 females) aged 0.5-94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0-12, 13-35, 36-50, 51-70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms.
In males, the highest sebum content was found on the forearm and the forehead in the age groups 36-50 (93.47 +/- 10.01 microg/cm(2)) and 51-70 years (9.16 +/- 1.95 microg/cm(2)), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13-35 (61.91 +/- 6.12 microg/cm(2)) and 51-70 years (7.54 +/- 2.55 microg/cm(2)). The forehead sebum content was higher in males aged 13-70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13-35 was higher than that in females (43.99 +/- 1.88 vs. 36.38 +/- 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm.
In a large Chinese cohort, the skin surface pH, sebum content and SC hydration vary with age, gender and body site.
To observe the efficacy of drug -coated balloon (DCB) in the treatment of long -segment arterial stenosis in lower extremity.
Were retrospectively analyzed in February 2017 to January 2018,the First ...Hospital Affiliated to China Medical University of vascular surgical treated 80 patients with lower limb sclerosis of arterial congee appearance (lesion length>10 cm), accept the DCB and stents (BMS) treatment, compared two groups of patients with preoperative and postoperative issue patency rate of target lesion, ABI, Rutherford, amputation rate and the change of clinical symptoms and quality of life.
There were 60 cases in DCB group,20 cases in BMS group and 80 cases in BMS group. The patency rate of DCB group was 83.33% and 75.00% at 6 and 12 months after operation. The patency rate was 85.00% and 65.00% in the BMS group at 6 and 12 months after surgery. ABI, walking distance, Rutherford grade and clinical symptoms were significantly improved in the two groups compared with those before surgery. During the oper
Abstract Background Few studies specifically focus on fatigue of (long-term) colorectal cancer (CRC) survivors or compare fatigue levels with a normative population. Association between surviving ...multiple primary cancers and fatigue is also explored. Methods Survivors diagnosed from 1998 to 2009 were identified from the Eindhoven Cancer Registry. In total, 3739 (79%) respondents and an age- and gender-matched normative population ( n = 338) completed questionnaires on fatigue and psychological distress. Results More survivors reported feeling fatigued than the normative population (39% versus 22%, p < 0.0001). Short-term survivors (<5 years post-diagnosis) had the highest mean fatigue scores compared with long-term survivors (⩾5 years post-diagnosis) or the normative population (21 ± 7 versus 20 ± 7 versus 18 ± 5, p < 0.0001, respectively). Having primary cancers prior to CRC was associated with more fatigue. Surgery + chemoradiation was independently associated with fatigue (odds ratio (OR): 1.63, 95% confidence interval (CI): 1.17–2.29, p = 0.004) as were anxiety (OR: 1.16, 95% CI: 1.12–1.19, p < 0.0001) and depressive symptoms (OR: 1.38, 95% CI: 1.33–1.43, p < 0.0001). Conclusions Fatigue is a significant problem, especially for short-term CRC survivors. The association between chemoradiation and fatigue suggests that patients could benefit from better information on treatment side-effects. When treating fatigue, clinical care should also focus on survivors’ psychological needs, especially survivors of multiple primary cancers.
Bulk nanocrystalline (NC) boron-doped refractory (VNbMoTaW)99B1 high entropy alloys (HEAs) were fabricated by mechanical alloying (MA) and high-pressure/high-temperature consolidation techniques. The ...consolidation was carried out between 800 and 1500 °C to examine the evolution of crystal phases, microstructure and mechanical performance. The bulk NC (VNbMoTaW)99B1 HEAs consolidated at 1350 °C are composed of a matrix with an average grain size of 43 nm and boride and carbide nanoprecipitates with an average particle size of 17 nm. The bulk NC (VNbMoTaW)99B1 HEAs exhibit ultrahigh hardness of 16.3 GPa (approx. triple that of their coarse-grained (CG) counterparts), an ultrahigh yield strength of 5.7 GPa (approx. five times that of their CG counterparts) under compression, and a total engineering strain of approx. 10%. The ultrahigh hardness and strength have four origins: solid solution, precipitation, grain boundary, and dislocation strengthening. The room-temperature resistivity of bulk NC (VNbMoTaW)99B1 is as high as ∼ 387 μΩ·cm, approx. five times that of their CG counterparts. This high resistivity can be related to the high volume fractions of grain boundaries and phase interfaces, the point defects and dislocations near grain boundaries, and the severe lattice distortions.
•Nanocrystalline boron-doped VNbMoTaW high-entropy alloy powders were prepared.•Bulk nanocrystalline VNbMoTaW alloys with boride nanoprecipitates were obtained.•The achieved alloys have an ultrahigh strength of 5.7 GPa and hardness of 16.3 GPa.•Grain boundary strengthening contributes 2.33 GPa to the ultrahigh strength.•The achieved alloys have an ultrahigh resistivity of 387 μΩ·cm.
V-based alloys such as V–4Cr–4Ti are one of the most promising candidate materials for fusion energy demonstration reactors, owing to their low activation and excellent resistance to neutron ...irradiation. However, conventional V-based alloys have poor high-temperature strength and creep resistance, resulting in a limited operating temperature window (400–700 °C). In this study, a series of low-activation VxFe65-xCr15Mn20 high-entropy alloys (HEAs) are designed and prepared by arc melting. Increasing the content of V of HEAs increases their nucleation rate during solidification, and thus decreases their grain size and increases their microhardness and strength. The yield strength of V50Fe15Cr15Mn20 HEA reaches 1189 MPa, which is mainly caused by the reduced grain size. The yield strength of V50Fe15Cr15Mn20 HEA between room temperature and 1000 °C is significantly higher than that of conventional V-based alloys. Such high high-temperature strength is explained by the high microstructural stability of the designed HEA. As a novel nuclear material, the present V50Fe15Cr15Mn20 HEA tested at a temperature of 900 °C still has a yield strength of 275 MPa, which is higher than that of conventional low-activation steels and V-based alloys.
•Low-activation vanadium-based high-entropy alloys are designed and prepared.•Vanadium-based high-entropy alloys exhibit superior strength.•High room-temperature strength is mainly caused by grain boundary strengthening.•High high-temperature strength is caused by suppressed growth of grain size.
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