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In this paper, we employ PCA and t-SNE analyses to gain deeper insights into the behavior of entangled and non-entangled mixing operators within the Quantum Approximate Optimization Algorithm (QAOA) at various depths. We utilize a dataset containing optimized parameters generated for max-cut problems with cyclic and complete configurations. This dataset encompasses the resulting RZ, RX, and RY parameters for QAOA models at different depths (1L, 2L, and 3L) with or without an entanglement stage within the mixing operator. Our findings reveal distinct behaviors when processing the different parameters with PCA and t-SNE. Specifically, most of the entangled QAOA models demonstrate an enhanced capacity to preserve information in the mapping, along with a greater level of correlated information detectable by PCA and t-SNE. Analyzing the overall mapping results, a clear differentiation emerges between entangled and non-entangled models. This distinction is quantified numerically through explained variance in PCA and Kullback-Leibler divergence (post-optimization) in t-SNE. These disparities are also visually evident in the mapping data produced by both methods, with certain entangled QAOA models displaying clustering effects in both visualization techniques.
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In this study, we investigate the position and momentum Shannon entropy, denoted as Sx and Sp, respectively, in the context of the fractional Schrödinger equation (FSE) for a hyperbolic double well potential (HDWP). We explore various values of the fractional derivative represented by k in our analysis. Our findings reveal intriguing behavior concerning the localization properties of the position entropy density, ρs(x), and the momentum entropy density, ρs(p), for low-lying states. Specifically, as the fractional derivative k decreases, ρs(x) becomes more localized, whereas ρs(p) becomes more delocalized. Moreover, we observe that as the derivative k decreases, the position entropy Sx decreases, while the momentum entropy Sp increases. In particular, the sum of these entropies consistently increases with decreasing fractional derivative k. It is noteworthy that, despite the increase in position Shannon entropy Sx and the decrease in momentum Shannon entropy Sp with an increase in the depth u of the HDWP, the Beckner-Bialynicki-Birula-Mycielski (BBM) inequality relation remains satisfied. Furthermore, we examine the Fisher entropy and its dependence on the depth u of the HDWP and the fractional derivative k. Our results indicate that the Fisher entropy increases as the depth u of the HDWP is increased and the fractional derivative k is decreased.
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In this work, we investigate the Shannon entropy of four recently proposed hyperbolic potentials through studying position and momentum entropies. Our analysis reveals that the wave functions of the single-well potentials U0,3 exhibit greater localization compared to the double-well potentials U1,2. This difference in localization arises from the depths of the single- and double-well potentials. Specifically, we observe that the position entropy density shows higher localization for the single-well potentials, while their momentum probability density becomes more delocalized. Conversely, the double-well potentials demonstrate the opposite behavior, with position entropy density being less localized and momentum probability density showing increased localization. Notably, our study also involves examining the Bialynicki-Birula and Mycielski (BBM) inequality, where we find that the Shannon entropies still satisfy this inequality for varying depths u¯. An intriguing observation is that the sum of position and momentum entropies increases with the variable u¯ for potentials U1,2,3, while for U0, the sum decreases with u¯. Additionally, the sum of the cases U0 and U3 almost remains constant within the relative value 0.01 as u¯ increases. Our study provides valuable insights into the Shannon entropy behavior for these hyperbolic potentials, shedding light on their localization characteristics and their relation to the potential depths. Finally, we extend our analysis to the Fisher entropy F¯x and find that it increases with the depth u¯ of the potential wells but F¯p decreases with the depth.
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According to the single-mode approximation applied to two different mo des, each associated with different uniformly accelerating reference frames, we present analytical expression of the Minkowski states for both the ground and first excited states. Applying such an approximation, we study the entanglement property of Bell and Greenberger-Horne-Zeilinger (GHZ) states formed by such states. The corresponding entanglement properties are described by studying negativity and von Neumann entropy. The degree of entanglement will be degraded when the acceleration parameters increase. We find that the greater the number of particles in the entangled system, the more stable the system that is studied by the von Neumann entropy. The present results will be reduced to those in the case of the uniformly accelerating reference frame.
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This work presents a quantum associative memory (Alpha-Beta HQAM) that uses the Hamming distance for pattern recovery. The proposal combines the Alpha-Beta associative memory, which reduces the dimensionality of patterns, with a quantum subroutine to calculate the Hamming distance in the recovery phase. Furthermore, patterns are initially stored in the memory as a quantum superposition in order to take advantage of its properties. Experiments testing the memory's viability and performance were implemented using IBM's Qiskit library.
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In this work, we study the quantum information entropies for two different types of hyperbolic single potential wells. We first study the behaviors of the moving particle subject to two different hyperbolic potential wells through focusing on their wave functions. The shapes of these hyperbolic potentials are similar, but we notice that their momentum entropy densities change along with the width of each potential and the magnitude of position entropy density decreases when the momentum entropy magnitude increases. On the other hand, we illustrate the behaviors of their position and momentum entropy densities. Finally, we show the variation of position and momentum entropies Sx and Sp with the change of the potential well depth u and verify that their sum still satisfies the BBM inequality relation.
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In this work we have studied the Shannon information entropy for two hyperbolic single-well potentials in the fractional Schrödinger equation (the fractional derivative number (0
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A Gram-stain-negative, rod-shaped and facultatively anaerobic strain, designated CG51T, was isolated from marine sediment collected from a coastal area in Weihai, PR China. Strain CG51T grew at 4-37 °C (optimum, 28-30 °C), with 1.0-6.0â% (w/v) NaCl (2.0-3.0â%) and at pH 6.0-8.5 (pH 7.0-7.5). The predominant fatty acids were iso-C15â:â0, anteiso-C15â:â0 and iso-C14â:â0. Major polar lipids included an unidentified lipid and a phospholipid. The respiratory quinone was MK-7 and the genomic DNA G+C content was 35.9 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences placed strain CG51T in the genus Labilibacter with the close relatives being Labilibacter marinus Y11T and Labilibacter aurantiacus HQYD1T, exhibiting 96.5 and 96.3â% 16S rRNA pairwise similarity, values which are clearly below the 98.7â% threshold value recommended for species demarcation. Based on the phylogenetic, physiological, chemotaxonomic and genetic data, strain CG51T represents a novel species within the genus Labilibacter, for which the name Labilibacter sediminis sp. nov. is proposed. The type strain is CG51T (=MCCC 1K03739T=JCM 33138T).
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Bacteroidetes/clasificación , Sedimentos Geológicos/microbiología , Filogenia , Agua de Mar/microbiología , Técnicas de Tipificación Bacteriana , Bacteroidetes/aislamiento & purificación , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMEN
A facultatively anaerobic and Gram-negative bacterium, designated strain PLHSC7-2T, was isolated from the gut of sea cucumber Apostichopusjaponicus that had been collected from the coastal area of Yantai, China. The cells were rod-shaped and motile by means of polar flagella. The novel isolate grew optimally at 28-30 °C, in the presence of 2.0-3.0â% (w/v) NaCl and at pH 7.0-7.5. The sole respiratory quinone was Q-8 and the major fatty acids were summed feature 3 (C16â:â1ω7c and/or C16â:â1ω6c), C16â:â0 and C17â:â0. The predominant polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain PLHSC7-2T was phylogenetically affiliated with the genus Motilimonas, and exhibited sequence similarity of 96.2â% toMotilimonas eburnea YH6T. The DNA G+C content was 45.5 mol%. On the basis of phenotypic , phylogenetic and genetic distinctiveness, strain PLHSC7-2T (=MCCC 1K03522T=KCTC 62589T) was classified as a novel species within the genus Motilimonas, for which the name Motilimonas pumila sp. nov. is proposed.
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Gammaproteobacteria/clasificación , Filogenia , Stichopus/microbiología , Animales , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Gammaproteobacteria/aislamiento & purificación , Fosfolípidos/química , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Selenoprotein S (SelS) is a transmembrane protein that is expressed in the liver, skeletal muscle, adipose tissue, pancreatic islets, kidney, and blood vessels. In addition to its transmembrane localization, SelS is also secreted from hepatoma HepG2 cells (but not L6 skeletal muscle cells, 3T3-L1 adipocytes, Min6 pancreatic ß cells and human embryonic kidney 293 cells) and has been detected in the serum of some human subjects, with a detection rate of 31.1 %. These findings prove that serum SelS is secreted by hepatocytes. However, whether vascularly expressed SelS can be secreted has not been reported. Transmembrane SelS has been suggested to play different roles in the pathogenesis and progression of diabetes mellitus (DM) and atherosclerosis (AS), but the association of secreted SelS with DM and macroangiopathy remains unclear. RESEARCH DESIGN AND METHODS: Supernatants were collected from human umbilical vein endothelial cells (HUVECs), human aortic vascular smooth muscle cells (HA/VSMCs) and human hepatoma HepG2 cells that were untransfected or transfected with the indicated plasmid and concentrated for western blotting. Serum samples were collected from 158 human subjects with or without type 2 DM (T2DM) and/or AS. Serum SelS levels were measured using an enzyme-linked immunosorbent assay. RESULTS: Secreted SelS was only detected in the supernatants of hepatoma HepG2 cells. The SelS detection rate among the 158 human serum samples was 100 %, and the average SelS level was 64.81 ng/dl. The serum SelS level in the isolated DM subjects was lower than the level in the healthy control subjects (52.66 ± 20.53 vs 70.40 ± 21.38 ng/dl). The serum SelS levels in the DM complicated with SAS subjects (67.73 ± 21.41 ng/dl) and AS subjects (71.69 ± 27.00 ng/dl) were significantly increased compared with the serum SelS level in the isolated DM subjects. There was a positive interaction effect between T2DM and AS on the serum SelS level (P = 0.002). Spearman correlation analysis showed that the serum SelS level was negatively correlated with fasting plasma glucose. CONCLUSIONS: Vascular endothelial and vascular smooth muscle cells could not secrete SelS. Serum SelS was primarily secreted by hepatocytes. SelS was universally detected in human serum samples, and the serum SelS level was associated with T2DM and its macrovascular complications. Thus, regulating liver and serum SelS levels might become a new strategy for the prevention and treatment of DM and its macrovascular complications.
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Aterosclerosis/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de la Membrana/metabolismo , Selenoproteínas/metabolismo , Tejido Adiposo/metabolismo , Adulto , Anciano , Aterosclerosis/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Islotes Pancreáticos/metabolismo , Hígado/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
The present paper reported the differential scanning calorimetry-thermogravimetry curves and the infrared (IR) absorption spectrometry under the temperature program analyzed by the combined simultaneous thermal analysis-IR spectrometer. The gas products of coal were identified by the IR spectrometry. This paper emphasized on the combustion at high temperature-IR absorption method, a convenient and accurate method, which measures the content of sulfur in coal indirectly through the determination of the content of sulfur dioxide in the mixed gas products by IR absorption. It was demonstrated, when the instrument was calibrated by varied pure compounds containing sulfur and certified reference materials (CRMs) for coal, that there was a large deviation in the measured sulfur contents. It indicates that the difference in chemical speciations of sulfur between CRMs and the analyte results in a systematic error. The time-IR absorption curve was utilized to analyze the composition of sulfur at low temperatures and high temperatures and then the sulfur content of coal sample was determined by using a CRM for coal with a close composition of sulfur. Therefore, the systematic error due to the difference in chemical speciations of sulfur between the CRM and analyte was eliminated. On the other hand, in this combustion at high temperature-IR absorption method, the mass of CRM and analyte were adjusted to assure the sulfur mass equal and then the CRM and the analyte were measured alternately. This single-point calibration method reduced the effect of the drift of the IR detector and improved the repeatability of results, compared with the conventional multi-point calibration method using the calibration curves of signal intensity vs sulfur mass. The sulfur content results and their standard deviations of an anthracite coal and a bituminous coal with a low sulfur content determined by this modified method were 0.345% (0.004%) and 0.372% (0.008%), respectively. The uncertainty (U, k =2) of sulfur contents of two coal samples was evaluated to be 0.019% and 0.021%, respectively. Two main modifications, namely the calibration using the coal CRM with a similar composition of low-temperature sulfur and high temperature sulfur, and the single-point calibration alternating CRM and analyte, endow the combustion at high temperature-IR absorption method with an accuracy obviously better than that of the ASTM method. Therefore, this modified method has a well potential in the analysis of sulfur content.
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This work introduces a quantum subroutine for computing the distance between two patterns and integrates it into two quantum versions of the kNN classifier algorithm: one proposed by Schuld et al. and the other proposed by Quezada et al. Notably, our proposed subroutine is tailored to be memory-efficient, requiring fewer qubits for data encoding, while maintaining the overall complexity for both QkNN versions. This research focuses on comparing the performance of the two quantum kNN algorithms using the original Hamming distance with qubit-encoded features and our proposed subroutine, which computes the distance using amplitude-encoded features. Results obtained from analyzing thirteen different datasets (Iris, Seeds, Raisin, Mine, Cryotherapy, Data Bank Authentication, Caesarian, Wine, Haberman, Transfusion, Immunotherapy, Balance Scale, and Glass) show that both algorithms benefit from the proposed subroutine, achieving at least a 50% reduction in the number of required qubits, while maintaining a similar overall performance. For Shuld's algorithm, the performance improved in Cryotherapy (68.89% accuracy compared to 64.44%) and Balance Scale (85.33% F1 score compared to 78.89%), was worse in Iris (86.0% accuracy compared to 95.33%) and Raisin (77.67% accuracy compared to 81.56%), and remained similar in the remaining nine datasets. While for Quezada's algorithm, the performance improved in Caesarian (68.89% F1 score compared to 58.22%), Haberman (69.94% F1 score compared to 62.31%) and Immunotherapy (76.88% F1 score compared to 69.67%), was worse in Iris (82.67% accuracy compared to 95.33%), Balance Scale (77.97% F1 score compared to 69.21%) and Glass (40.04% F1 score compared to 28.79%), and remained similar in the remaining seven datasets.
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Background: Surgery is the primary treatment for locally advanced thyroid cancer. For some cases, R0/R1 resection could not be achieved at initial diagnosis and neoadjuvant treatment would be an option. Anlotinib is a multitarget tyrosine kinase inhibitor, which demonstrated antitumor activity in radioiodine-refractory differentiated thyroid cancer and medullary thyroid cancer. We aimed to evaluate the efficacy and safety of anlotinib in locally advanced thyroid cancer in the neoadjuvant setting. Methods: This single-arm phase II study investigated the efficacy and safety of anlotinib (12 mg orally daily, 2 weeks on/1 week off) for 2-6 cycles in patients with locally advanced thyroid cancer in the neoadjuvant setting. The key eligibility criteria included age 14-80 years old; locally advanced thyroid cancer that would benefit from surgery, and at least one measurable lesion. Operable patients received surgery after neoadjuvant treatment. The primary endpoint was objective response rate (ORR). Results: A total of 13 patients were enrolled and received an average of 3.5 cycles of anlotinib treatment. The ORR of anlotinib was 76.9% (95% confidence interval: 46.2-95.0%). The R0/R1 resection rate in the intent-to-treat population was 61.5% and in the per-protocol population was 72.7%. The median time to response was 61.5 days, and the disease control rate at 18 weeks was 92.3%. No patients had blood transfusion or tracheotomy. Most adverse events (AEs) were grade 1 or 2 and tended to discontinue when neoadjuvant treatment ceased. Common AEs of all grades were hypertension (76.9%), hypertriglyceridemia (69.2%), proteinuria (53.8%), thyrotropin increase (53.8%), cholesterol elevation (53.8%), and hand-foot syndrome (38.5%). Conclusions: Anlotinib demonstrated antitumor activity in the neoadjuvant treatment and the majority of patients achieved R0/R1 resection. AEs were consistent with the known anlotinib AE profile. These results suggest that anlotinib neoadjuvant treatment represents a new option for locally advanced thyroid cancer. Clinical Trial Registration Number: NCT04309136.
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Antineoplásicos/uso terapéutico , Indoles/uso terapéutico , Quinolinas/uso terapéutico , Neoplasias de la Tiroides/terapia , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disección del Cuello , Terapia Neoadyuvante , TiroidectomíaRESUMEN
The exact solutions to a one-dimensional harmonic oscillator plus a non-polynomial interaction aâ x 2 + bâ x 2/(1 + câ x 2) (a > 0, c > 0) are given by the confluent Heun functions H c (α, ß, γ, δ, η;z). The minimum value of the potential well is calculated as V min ( x ) = - ( a + | b | - 2 a | b | ) / c at x = ± [ ( | b | / a - 1 ) / c ] 1 / 2 (|b| > a) for the double-well case (b < 0). We illustrate the wave functions through varying the potential parameters a, b, c and show that they are pulled back to the origin when the potential parameter b increases for given values of a and c. However, we find that the wave peaks are concave to the origin as the parameter |b| is increased.
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OBJECTIVE: Compared with Occident's data, the incidence of Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinomas (OPSCCs) had been reported as relatively low in Mainland China. The objective of this study was to report the integrated prevalence of HPV and Epstein-Barr virus (EBV), and further evaluate the different behaviors of HPV-positive and -negative OPSCCs in eastern China. METHODS: In a cohort of 170 nonmetastatic OPSCCs treated from January 2007 to July 2019, p16 protein expression, HPV genotypes, and Epstein-Barr virus-encoded RNA (EBER) were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). The clinical and pathologic findings were further collected and analyzed to comprehensively reveal the behaviors of Chinese OPSCCs. RESULTS: Out of the 170 tumor tissues evaluated, 57.6% (98) samples had positive p16 expressions. A total of 65.1% (99/152) samples had positive HPV genotypes, besides HPV16 (92/152), HPV11, 18, 33, 53, and 58 were also detected. The positive rate of EBER was 7.2% (9/124), and the co-infection rate of EBV/HPV was 4.0%. Related to the unequal distributions of p16 expression, HPV-related tumors arisen from tonsillar and non-tonsillar accounted for 68.8% (75/109) and 37.7% (23/61) of their cases, respectively (P < .001). With a median follow-up time of 13.1 months, significant survival advantages of HPV-related OSPCC were observed; 1-year OS, PFS, RFS, and MFS were 83.2% vs 96.7% (P < .001), 71.6% vs 96.2% (P < .001), 77.7% vs 96.2% (P = .002), and 90.4% vs 100.0% (P = .024) in p16-negative and -positive cases, respectively. CONCLUSIONS: The relative percent of HPV-positive OPSCCs in this study is close to the positive rate in many Western countries and a strong predilection was discovered for the tonsillar. The EBV infection and co-infection of HPV/EBV were largely low. The prognosis of HPV-positive OSPCCs was more favorable than its negative counterpart.
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Coinfección , Infecciones por Virus de Epstein-Barr/epidemiología , Herpesvirus Humano 4/genética , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , ARN Viral/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Neoplasias Tonsilares/virología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , China/epidemiología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/virología , Femenino , Genotipo , Interacciones Huésped-Patógeno , Humanos , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Prevalencia , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/epidemiología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias Tonsilares/diagnóstico , Neoplasias Tonsilares/epidemiología , Neoplasias Tonsilares/terapia , Adulto JovenRESUMEN
Heterostructures with a rich phase boundary are attractive for surface-mediated microwave absorption (MA) materials. However, understanding the MA mechanisms behind the heterogeneous interface remains a challenge. Herein, a phosphine (PH3) vapor-assisted phase and structure engineering strategy was proposed to construct three-dimensional (3D) porous Ni12P5/Ni2P heterostructures as microwave absorbers and explore the role of the heterointerface in MA performance. The results indicated that the heterogeneous interface between Ni12P5 and Ni2P not only creates sufficient lattice defects for inducing dipolar polarization but also triggers uneven spatial charge distribution for enhancing interface polarization. Furthermore, the porous structure and proper component could provide an abundant heterogeneous interface to strengthen the above polarization relaxation process, thereby greatly optimizing the electromagnetic parameters and improving the MA performance. Profited by 3D porous heterostructure design, P400 could achieve the maximum reflection loss of -50.06 dB and an absorption bandwidth of 3.30 GHz with an ultrathin thickness of 1.20 mm. Furthermore, simulation results confirmed its superior ability (14.97 dB m2 at 90°) to reduce the radar cross section in practical applications. This finding may shed light on the understanding and design of advanced heterogeneous MA materials.
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Benefits of subdividing small-differentiated thyroid carcinoma (sDTC) by tumor size are controversial. We conducted a meta-analysis to investigate whether tumor size is associated with prognosis of sDTC. PubMed and Web of Science databases were searched from their inception to September 2018. The identified studies according to the inclusion/exclusion criteria were analyzed using fixed/random-effects models. Data were calculated and results of the meta-analysis were expressed as odd ratio (OR). sDTC was classified as S1 (≤1 cm) and S2 (>1 cm and ≤2 cm). A systematic analysis was performed to compare the difference of recurrence, survival and clinicopathological factors between the two subgroups of sDTC (S1 vs. S2). A total of 21 studies published between 2004 and 2017 enrolling 219,291 patients were included. Findings showed that, S2 was associated with higher recurrence risk compared with S1 (OR=1.575, 95% CI=1.428-1.738; P<0.05). There was no statistical difference in survival between S1 and S2, but significant statistical heterogeneity (OR=1.160, 95% CI=0.810-1.662; P=0.448; I2=75.8%). Meta-regression analysis revealed publication year potentially caused the heterogeneity (P<0.05). Comparison of small papillary thyroid carcinoma alone agreed with the results of sDTC. T1b increased the risk of recurrence (OR=1.520; 95% CI=1.072-2.155; P<0.05) and death (OR=1.504; 95% CI 1.353-1.672; P<0.05) compared with T1a. S2 associated with extrathyroidal extension (OR=2.575; 95% CI=1.603-4.135; P<0.05), bilaterality (OR=2.278; 95% CI=1.905-2.723; P<0.05), vascular invasion (OR=4.494; 95% CI=2.812-7.183; P<0.05) and lymph node metastases (OR=1.12; 95% CI=1.10-1.14; P<0.05). Our analysis suggested it is necessary to subdivide sDTC into S1 and S2 owing to their different effects on prognosis, especially recurrence.
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Differentiated thyroid cancer (DTC) is associated with the highest propensity for lymph node metastases, given the significant morbidity associated with sacrificing the spinal accessory nerve, surgeons increasingly looked to minimizing functional deficits while maintaining oncologic outcome. We have detailed the technique of a selective neck dissection with more attention to preserving the cervical sensory nerves since 1999 in Fudan University Shanghai Cancer Center. We found that the radical dissection with preservation of the cutaneous branches including the great auricular nerve, the less occipital nerve and the supraclavicular nerve can maximally decrease the complications of paresthesia and dysesthesia postoperatively in the lower neck, the shoulders and the area around the ear in DTC cases when indications were allowed. As long as the principles of cancer surgery are strictly followed, our approach guarantees radical tumor removal and exhibit more functional preservation.
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In response to mild ischemic stress, the brain elicits endogenous survival mechanisms to protect cells against a subsequent lethal ischemic stress, referred to as ischemic tolerance. The molecular signals that mediate this protection are thought to involve the expression and activation of multiple kinases, including protein kinase C (PKC). Here we demonstrate that epsilonPKC mediates cerebral ischemic tolerance in vivo. Systemic delivery of psiepsilonRACK, an epsilonPKC-selective peptide activator, confers neuroprotection against a subsequent cerebral ischemic event when delivered immediately prior to stroke. In addition, activation of epsilonPKC by psiepsilonRACK treatment decreases vascular tone in vivo, as demonstrated by a reduction in microvascular cerebral blood flow. Here we demonstrate the role of acute and transient epsilonPKC in early cerebral tolerance in vivo and suggest that extra-parenchymal mechanisms, such as vasoconstriction, may contribute to the conferred protection.
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Isquemia Encefálica , Proteína Quinasa C-epsilon/fisiología , Daño por Reperfusión/metabolismo , Animales , Circulación Cerebrovascular/efectos de los fármacos , Activación Enzimática , Inducción Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Masculino , Técnicas de Cultivo de Órganos , Péptidos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/prevención & control , Factores de TiempoRESUMEN
Verteporfin, a FDA approved second-generation photosensitizer, has been demonstrated to have anticancer activity in various tumors, but not including papillary thyroid cancer (PTC). In current pre-clinical pilot study, we investigate the effect of verteporfin on proliferation, apoptosis, cell cycle and tumor growth of PTC. Our results indicate verteporfin attenuates cell proliferation, arrests cell cycle in G2/S phase and induces apoptosis of PTC cells. Moreover, treatment of verteporfin dramatically suppresses tumor growth from PTC cells in xenograft mouse model. We further illustrate that exposure to MEK inhibitor U0126 inactivates phosphorylation of ERK1/2 and MEK in verteporfin-treated PTC cells. These data suggest verteporfin exhibits inhibitory effect on PTC cells proliferation and cell cycle partially via ERK1/2 signalling pathway, which strongly encourages the further application of verteporfin in the treatment against PTC.