Neoadjuvant Chemotherapy with FOLFOX4 Regimen to Treat Advanced Gastric Cancer Improves Survival without Increasing Adverse Events: A Retrospective Cohort Study from a Chinese Center

Background/Aim. To evaluate the clinical efficacy of FOLFOX4 (5-fluomumcil/leucovorin combined and oxaliplatin) neoadjuvant chemotherapy for advanced gastric cancer (AGC). Patients and Methods. Fifty-eight AGC patients were enrolled in this retrospective cohort study, 23 in the neoadjuvant group and 35 in the adjuvant group. R0 resection, survival, and adverse events were compared. Results. The two groups were well-matched, with no significant differences in R0 resection rate (82.6% versus 82.0%) and number of lymph nodes dissection (16 (0–49) versus 13 (3–40)) between the two groups (P>0.05). The number of lymph node metastases in the neoadjuvant group (3 (0–14)) was significantly fewer than that in the adjuvant group (6 (0–27)) (P=0.04). The neoadjuvant group had significantly better median overall survival (29.0 versus 22.0 months) and 3-year survival rate (73.9% versus 40.0%) than the adjuvant group (P=0.013). The positive expression rate of Ki-67 in the neoadjuvant group (40.0%, 8/20) was lower than that in the adjuvant group (74.2%, 23/31; P=0.015). Conclusion. The FOLFOX4 neoadjuvant chemotherapy could improve survival without increasing adverse events in patients with AGC

Effect of deletion of the rgpA gene on selected virulence of Porphyromonas gingivalis

AbstractBackground/purposeThe most potent virulence factors of the periodontal pathogen Porphyromonas gingivalis are gingipains, three cysteine proteases (RgpA, RgpB, and Kgp) that bind and cleave a wide range of host proteins. Considerable proof indicates that RgpA contributes to the entire virulence of the organism and increases the risk of periodontal disease by disrupting the host immune defense and destroying the host tissue. However, the functional significance of this proteinase is incompletely understood. It is important to analyze the effect of arginine-specific gingipain A gene (rgpA) on selected virulence and physiological properties of P. gingivalis.Materials and methodsElectroporation and homologous recombination were used to construct an rgpA mutant of P. gingivalis ATCC33277. The mutant was verified by polymerase chain reaction and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Cell structures of the mutant were examined by transmission electron microscopy and homotypic biofilm formation was examined by confocal laser scanning microscopy.ResultsGene analysis revealed that the rgpA gene was deleted and replaced by a drug resistance gene marker. The defect of the gene resulted in a complete loss of RgpA proteinase, a reduction of out membrane vesicles and hemagglutination, and an increase in homotypic biofilm formation.ConclusionOur data indicate that an rgpA gene deficient strain of P. gingivalis is successfully isolated. RgpA may have a variety of physiological and pathological roles in P. gingivalis

5-(1H-Inden-2-yl)-1,3-benzodioxole

In the title compound, C16H12O2, the non-H atoms are coplanar with a mean r.m.s. deviation of 0.0260 (2) Å. The deviations of the bond angles from normal values at the indenyl junction C atom and the indenyl bridgehead C atom nearest the junction are imposed by the five-membered ring geometry. Due to conjugation, the single bond linking the two ring systems [1.455 (3) Å] is significantly shorter than the formal single bonds in the five-membered carbocyclic ring [1.500 (3) and 1.489 (3) Å]

Prevailing PA mutation K356R in avian influenza H9N2 virus increases mammalian replication and pathogenicity

Adaptation of the viral polymerase complex comprising PB1, PB2, and PA is necessary for efficient influenza A virus replication in new host species. We found that PA mutation K356R (PA-K356R) has become predominant since 2014 in avian H9N2 viruses in China as with seasonal human H1N1 viruses. The same mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses whose six internal gene segments are derived from the H9N2 virus. We further demonstrated the mammalian adaptive functionality of the PA-K356R mutation. Avian H9N2 virus with the PA-K356R mutation in human A549 cells showed increased nuclear accumulation of PA and increased viral polymerase activity that resulted in elevated levels of viral transcription and virus output. The same mutant virus in mice also enhanced virus replication and caused lethal infection. In addition, combined mutation of PA-K356R and PB2-E627K, a well-known mammalian adaptive marker, in the H9N2 virus showed further cooperative increases in virus production and severity of infection in vitro and in vivo. In summary, PA-K356R behaves as a novel mammalian tropism mutation, which, along with other mutations such as PB2-E627K, might render avian H9N2 viruses adapted for human infection

Polymer flooding – Does Microscopic Displacement Efficiency Matter?

Polymer flooding is an enhanced oil recovery (EOR) technique that aims to enhance the stability of the flood front in order to increase sweep efficiency and thereby increase hydrocarbon recovery. Polymer flooding studies often focus on large-scale sweep efficiency and neglect the impact of the pore-scale displacement efficiency of the multi-phase flow. This work explores the pore-scale behavior of water vs polymer flooding, and examines the impact of rock surface wettability on the microscopic displacement efficiency using digital rock physics. In this study, a micro-CT image of a sandstone rock sample was numerically simulated for both water and polymer flooding under oil-wet and water-wet conditions. All simulations were performed at a capillary number of 1E-5, corresponding to a capillary dominated flow regime. Results of the four two-phase flow imbibition simulations are analyzed with respect to displacement character, water phase break-through, viscous/capillary fingering, and trapped oil. In the water-wet scenario, differences between water flood and polymer flood are small, with the flood front giving a piston-like displacement and breakthrough occurring at about 0.4 pore volume (PV) for both types of injected fluid. On the other hand, for the oil-wet scenario, water flood and polymer flood show significant differences. In the water flood, fingering occurs and much of the oil is bypassed early on, whereas the polymer flood displaces more oil and thereby provides better microscopic sweep efficiency throughout the flood and especially around breakthrough. Overall the results for this rock sample indicate that water flood and polymer flood provide similar recovery for a water-wet condition, while the reduced mobility ratio of polymer flood gives significantly improved recovery for an oil-wet condition by avoiding the onset of microscopic (pore-scale) fingering that occurs in the water flood. This study suggests that depending on the rock-fluid conditions, the use of polymer can impact microscopic sweep efficiency, in addition to the well-known effect on macroscopic sweep behavior.La inyección de polímeros es una técnica de recobro mejorado de petróleo (EOR) que tiene como objetivo mejorar la estabilidad del frente de inyección para aumentar la eficiencia del desplazamiento de hidrocarburos y, por lo tanto, incrementar el factor de recobro. Lo estudios de inyección de polímeros a menudo se centran en la eficiencia del desplazamiento a gran escala e ignoran el impacto de los mecanismos de desplazamiento a escala microscópica, y rara vez evalúan la variabilidad de parámetros de flujo multifásico en el medio poroso. Este trabajo explora el comportamiento del agua contra la inyección de polímeros en el medio poroso, y examina el impacto de la humectabilidad de la superficie de la roca en la eficiencia de desplazamiento microscópico, utilizando tomografía computarizada de rayos X en muestras de roca. En este estudio, se simuló numéricamente una imagen de microtomografía computarizada de una muestra de roca arenisca, para un proceso de inyección de agua y polímeros en condiciones de mojabilidad al aceite y al agua. Todas las simulaciones se realizaron a un número capilar de 1E-5, correspondiente a un régimen de flujo dominado por fuerzas capilares y que es típico del flujo en yacimientos de hidrocarburos. Los resultados de las cuatro simulaciones de imbibición de flujo de dos fases se analizan con respecto al carácter desplazante, el avance de la fase acuosa, la digitación viscosa y capilar, y el aceite atrapado. En el escenario de mojabilidad al agua, las diferencias entre la inyección de agua y la inyección de polímeros son pequeñas, dado que el frente de inyección produce un  desplazamiento en forma de pistón y un avance que se produce a aproximadamente 0,4 volúmenes porosos para ambos tipos de fluido inyectado. Por otro lado, para el escenario de mojabilidad al petróleo, la inyección de agua y la inyección de polímeros muestran diferencias significativas. En la inyección de agua, se produce digitación y gran parte del petróleo se pasa por alto al principio; mientras que la inyección de polímeros desplaza más aceite y, por lo tanto, proporciona una mejor eficiencia de desplazamiento microscópico durante la inyección, especialmente alrededor de la ruptura. En general, los resultados para esta muestra de roca indican que la inyección de agua y la inyección de polímeros proporcionan un efecto de recobro similar para una condición de mojabilidad al agua, mientras que la relación de movilidad reducida de la inyección de polímeros proporciona un efecto de recobro significativamente mejorado para una condición de mojabilidad al aceite, al evitar la aparición de digitación microscópica (a escala de poro) que se produce en la inyección de agua. Este estudio sugiere que, dependiendo de las condiciones roca-fluido, el uso del polímero puede impactar la eficiencia de desplazamiento microscópico, además del efecto conocido sobre el comportamiento del desplazamiento macroscópico

Silica-Lipid Hybrid Microparticles as Efficient Vehicles for Enhanced Stability and Bioaccessibility of Curcumin

Kurkumin je aktivni sastojak koji ima višestruku ulogu, no njegova je uporaba ograničena zbog slabe topljivosti u vodi i stabilnosti, a time i slabe biološke raspoloživosti. Stoga je svrha ovoga rada bila osmisliti kako zaobići ta ograničenja. Postupkom emulgiranja dobivena je nanoemulzija s kurkuminom, a nakon toga sušenjem u vakuumu hibridne mikročestice nanoemulzije u silicijevom dioksidu. Udjel kurkumina u nanoemulziji bio je (0,30±0,02) %, a u mikročesticama (0,67±0,02) %. FTIR i XDR analizom utvrđeno je da je kurkumin u mikročesticama inkapsuliran u poroznom amorfnom silicijevom dioksidu. Antioksidacijska aktivnost kurkumina in vitro nije se smanjila nakon inkapsulacije. Simulacijom probave in vitro utvrđeno je da je biološka raspoloživost kurkumina u nanoemulziji i mikročesticama bila veća nego u kontrolnom uzorku. Stabilnost mikročestica ostala je ista tijekom 6 tjedana skladištenja u mraku pri temperaturama od 4, 25 i 40 °C. Osim toga, pokazalo se da su pri izlaganju svjetlosti, mikročestice imale bolju kemijsku stabilnost od nanoemulzije. Pri koncentraciji nanoemulzije manjoj od 45 μg/mL preživljavanje stanica bilo je veće od 80 %. Stoga možemo zaključiti da mikročestice mogu poslužiti kao nosači kurkumina te poboljšati njegovu topljivost, stabilnost pri izlaganju svjetlosti te biološku raspoloživost.Curcumin is an active ingredient with multiple functions, but its application is often restricted due to its poor water solubility, weak stability, and consequently low bioaccessibility. Based on this, the aim of this work is to develop a new vehicle to overcome these restrictions. Here we developed a curcumin-loaded nanoemulsion and then curcumin-loaded silica-lipid hybrid microparticles through emulsification and vacuum drying, respectively. The loading of curcumin in the nanoemulsion and microparticles was (0.30±0.02) and (0.67±0.02) %, respectively. FTIR and XRD analyses of microparticles revealed that curcumin was encapsulated in porous, amorphous silica. In vitro antioxidant activities showed that the encapsulation would not affect the antioxidant activity of curcumin. In vitro simulated digestion indicated that nanoemulsion and microparticles had higher curcumin bioaccessibility than the control group. The storage stability of microparticles remained the same during 6 weeks in the dark at 4, 25 and 40 °C. Moreover, the microparticles had a better chemical stability than nanoemulsion under the light. The cell viability was over 80 % when the concentration of nanocarriers was less than 45 μg/mL. Hence, the microparticles could be a promising means to load curcumin and improve its solubility, light stability and bioaccessibilit

Recommendation for a contouring method and atlas of organs at risk in nasopharyngeal carcinoma patients receiving intensity-modulated radiotherapy

Background and purpose To recommend contouring methods and atlas of organs at risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, in order to help reach a consensus on interpretations of OARs delineation. Methods and materials Two to four contouring methods for the middle ear, inner ear, temporal lobe, parotid gland and spinal cord were identified via systematic literature review; their volumes and dosimetric parameters were compared in 41 patients. Areas under the receiver operating characteristic curves for temporal lobe contouring were compared in 21 patients with unilateral temporal lobe necrosis (TLN). Results Various contouring methods for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead to different volumes and dosimetric parameters (P < 0.05). For TLN, D1 of PRV was the most relevant dosimetric parameter and 64 Gy was the critical point. We suggest contouring for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord. A CT-MRI fusion atlas comprising 33 OARs was developed. Conclusions Different dosimetric parameters may hinder the dosimetric research. The present recommendation and atlas, may help reach a consensus on subjective interpretation of OARs delineation to reduce inter-institutional differences in NPC patients. © 2013 Elsevier Ireland Ltd. All rights reserved.published_or_final_versio

Enhanced stability of M1 protein mediated by a phospho-resistant mutation promotes the replication of prevailing avian influenza virus in mammals

Avian influenza virus (AIV) can evolve multiple strategies to combat host antiviral defenses and establish efficient infectivity in mammals, including humans. H9N2 AIV and its reassortants (such as H5N6 and H7N9 viruses) pose an increasing threat to human health; however, the mechanisms involved in their increased virulence remain poorly understood. We previously reported that the M1 mutation T37A has become predominant among chicken H9N2 isolates in China. Here, we report that, since 2010, this mutation has also been found in the majority of human isolates of H9N2 AIV and its emerging reassortants. The T37A mutation of M1 protein enhances the replication of H9N2 AIVs in mice and in human cells. Interestingly, having A37 instead of T37 increases the M1 protein stability and resistance to proteasomal degradation. Moreover, T37 of the H9N2 M1 protein is phosphorylated by protein kinase G (PKG), and this phosphorylation induces the rapid degradation of M1 and reduces viral replication. Similar effects are also observed in the novel H5N6 virus. Additionally, ubiquitination at K187 contributes to M1-37T degradation and decreased replication of the virus harboring T37 in the M1 protein. The prevailing AIVs thereby evolve a phosphoresistant mutation in the M1 protein to avoid viral protein degradation by host factors, which is advantageous in terms of replication in mammalian hosts

Chiral edge waves in a dance-based human topological insulator

Topological insulators are insulators in the bulk but feature chiral energy propagation along the boundary. This property is topological in nature and therefore robust to disorder. Originally discovered in electronic materials, topologically protected boundary transport has since been observed in many other physical systems. Thus, it is natural to ask whether this phenomenon finds relevance in a broader context. We choreograph a dance in which a group of humans, arranged on a square grid, behave as a topological insulator. The dance features unidirectional flow of movement through dancers on the lattice edge. This effect persists when people are removed from the dance floor. Our work extends the applicability of wave physics to the performance arts