Aim: This study was to determine the roles of inflammatory cytokines in paraventricular nucleus (PVN) in modulating sympathetic activity, blood pressure and cardiac sympathetic afferent reflex ...(CSAR).
Methods: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats with bilateral sinoaortic denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of bradykinin (BK). The levels of inflammatory cytokines were measured with ELISA.
Results: The PVN microinjection of pro‐inflammatory cytokines (PIC), tumour necrosis factor (TNF)‐α or interleukin (IL)‐1β, increased the baseline MAP and RSNA, and enhanced the CSAR. Anti‐inflammatory cytokines (AIC), IL‐4 or IL‐13, in the PVN only increased the baseline MAP. In the rats pretreated with TNF‐α or IL‐1β but not in the rats pretreated with IL‐4 or IL‐13, sub‐response dose of angiotensin II caused significant increases in the MAP and RSNA and enhancement in the CSAR. AT1 receptor antagonist losartan in the PVN attenuated the effects of angiotensin II, TNF‐α and IL‐1β, but not the effects of IL‐4 and IL‐13. Stimulation of cardiac sympathetic afferents with epicardial application of BK increased the levels of TNF‐α, IL‐1β but not IL‐4 in the PVN.
Conclusion: TNF‐α or IL‐1β in the PVN increases blood pressure and sympathetic outflow and enhances the CSAR, which is partially dependent on the AT1 receptors, while IL‐4 or IL‐13 in the PVN only increases blood pressure. There is a synergetic effect of Ang II with TNF‐α or IL‐1β on blood pressure, sympathetic activity and CSAR.
Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, ...genetic origin, and clinical management remain controversial.
Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes.
The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0–11.2).
The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.
•The adenocarcinoma component and squamous cell carcinoma component of adenosquamous carcinoma share a common clonal origin.•High incidence of trunk EGFR and TP53 mutation were noted in adenosqumous cell carcinoma, while the overall genomic profile of adenosqumous cell carcinoma is more similar to adenocarcinoma than squmous cell carcinoma.•EGFR-TKIs should be the standard first-line therapy for advanced stage adenosquamous carcinoma with EGFR mutation.
It is difficult to accurately visualize internal structure and characterize progressive fracture process during rock failure due to the heterogeneous and opaque features of rock. This paper focuses ...on providing two methods, i.e., 3D printing (3DP) and 3D numerical modelling, to replicate internal defects and study the mechanical and fracture behaviours of rock in combination with X-ray computerized tomography (micro-CT). On one hand, Stereolithography 3DP combined with the X-ray micro-CT and 3D reconstruction techniques were applied to replicate natural volcanic rocks using 3DP resin. Uniaxial compression and Brazilian disc tests were, subsequently, performed to characterize and visualize the mechanical and fracture properties of the 3DP rock. On the other hand, the digital image processing technique was adopted to integrate the microstructures of the natural volcanic rock into the rock failure process analysis code (RFPA3D-digital) for characterizing the failure behaviour of rock under uniaxial compression and tension. The results showed that both the 3DP samples and the 3D numerical models can successfully replicate the internal defects and micro-structures identical to those of the natural prototype volcanic rock. The mechanical properties of the 3DP samples and the 3D numerical models, including compressive and tensile strength and the Poisson's ratio, and fracture properties are testified to be similar to those of the prototype rocks. Visualization analysis of the progressive fracture process demonstrated that the initial internal voids and cracks dominate the spatial fracture evolution and failure patterns within the rock. The proposed methods provide a promising means to quantify, replicate and visualize the pre-existing defects and mirco-structures, and to understand their influences on the mechanical and fracture behaviour of rock under different loading conditions, facilitating better understanding of failure mechanism of rocks.
SUMMARY
Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of ...creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.
Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing ...partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
The debris flow is one of the geological hazards; its occurrence is complex, fuzzy, and random. And it is affected by many indices; a new multi-index assessment method is proposed to analyze the risk ...level of debris flow based on the entropy weight-normal cloud model in Banshanmen gully. The index weight is calculated by using the entropy weight method. Then, the certainty degree of each index belonging to the corresponding cloud is obtained by using the cloud model. The final risk level of debris flow is determined according to the synthetic certainty degree. The conclusions are drawn that the method is feasible and accurate rate of risk estimation for debris flow is very high, so a new method and thoughts for the risk assessment of debris flow can be provided in the future.
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