Prognostic value of desmoplastic stromal reaction,tumor budding and tumor-stroma ratio in stage II colorectal cancer

BackgroundExisting high-risk factors are insufficient to accurately predict the postoperative recurrence risk of stage II colorectal cancer (CRC). The discovery of additional prognostic markers may be the key to improving the current status of stage II CRC treatment. The present study aimed to evaluate the relationship among desmoplastic reaction (DR), tumor budding (TBd), the tumor-stroma ratio (TSR) and their prognostic value for relapse-free survival (RFS).MethodsIn this study, 207 patients with histologically confirmed stage II CRC from January 2012 to August 2018 were retrospectively reviewed from a single center; the cohort was divided into subgroups based on low or high TSR, and low, intermediate or high DR and TBd. Kaplan–Meier curve analysis and log-rank test were applied to examine RFS among subgroups. Univariate and multivariate Cox proportional hazards analyses were used to identify independent factors associated with RFS, and a nomogram was subsequently developed.ResultsAbnormal CA242, CEA, T4 stage, presence of hypertension, internal obstruction or perforation (IOP), lymphovascular or/and perineural invasion (PNI), number of nodes examined less than 12, low-frequency microsatellite instability (MSI-L), higher Ki-67 and immature DR were associated with a lower RFS. In multivariable analysis, DR (HR =2.111; 95% CI: 1.184–3.766; P=0.011), LVI (HR =1.919; 95% CI: 1.004–3.669; P=0.049) and PNI (HR =2.724; 95% CI: 1.362–5.448; P=0.005) were prognostic factors for RFS. On this basis, a nomogram that integrated DR and clinicopathologic predictors for predicting RFS passed the calibration and had an area under the curve of 0.826.ConclusionsThe prognostic significance of DR outperformed TBd and TSR, therefore, we recommend adding DR as a biomarker in routine pathological reports. The novel nomogram combining these factors may be used as a reliable and effective tool for the prediction of RFS in stage II CRC, thus helping optimize therapeutic regimens under cooperation of oncologists and surgeons. Further multicentric studies are required for validation of this novel, simple and cost-effective prognostic model.     

Selection of endpoints in breast cancer clinical trials: a qualitative study of key trial stakeholders

Clinical trial endpoints are fundamental for evaluating the safety and efficacy of cancer therapies, yet it is not well understood how they are selected or the role of stakeholder groups in deciding endpoints. This study aimed to explore how clinical trial endpoints are selected in breast cancer trials of anti-cancer drugs through semi structured interviews with purposively selected stakeholders involved in breast cancer clinical trials (clinicians, consumers, pharmaceutical company representatives, and members of drug regulatory agencies). Participants were asked to describe the process of selecting trial endpoints. Interviews were transcribed verbatim and analysed using inductive thematic analysis supported by NVivo software. Saturation of the main themes was reached and the final sample included 25 participants from 14 countries (9 clinicians, 7 consumers, 5 members of regulatory agencies, 4 pharmaceutical company representatives). Pharmaceutical companies were almost always identified as the main decision maker. While most consumers and pharmaceutical company representatives felt clinicians and consumers influenced trial design, some clinicians and regulators reported consumers and clinicians had little influence. Factors identified as important considerations in determining trial endpoints included the main goal of the trial, established standardised endpoints, resources, and the investigational agent studied. All pharmaceutical advisors reported that meeting the requirements for regulatory approval was the major factor considered. Clinical trial endpoint selection is largely decided by the pharmaceutical industry, driven by requirements for regulatory approval. Given the limited influence from clinicians and consumers, guidance by regulatory agencies will be important for future inclusion of novel endpoints in clinical trials.     

Research on the Properties and Mechanism of Carbon Nanotubes Reinforced Low-Carbon Ecological Cement-Based Materials

SAC (sulfoaluminate cement) has become a research hotspot as a low-carbon ecological cement. In addition, multi-walled carbon nanotubes have good thermal, mechanical, and electrical properties and can serve as excellent nano-reinforced cement-based fillers. This study explored the dispersion of carbon nanotubes (CNTs) and researched the effect of CNTs on the mechanical properties, hydration process, hydration products, and microstructure of SAC paste, and the mechanism of CNT-enhanced SAC paste was revealed. The results showed that the mechanical properties of SAC paste were significantly improved after the addition of CNTs. When the CNT content was 0.05%, 0.1%, and 0.15%, the compressive strength after 28 d was increased by 13.2%, 18.3%, and 22.5%, respectively; compared with the C0 group (without CNTs), the flexural strength increased by 8.2%, 11.3%, and 14.4%, respectively. The addition of CNTs accelerated the hydration process of SAC paste. Due to the adsorption effect and nucleation effect of CNTs, more hydration products were generated, filling the matrix’s pores and improving its compactness. The mechanism of CNTs enhanced SAC paste was revealed. CNTs and hydration products co-filled the pores, including AFt (ettringite) and AH₃ (gibbsite). CNTs improve the mechanical properties of SAC paste through filling, bridging, crack bending, deflection, pulling out, and pulling off.     

Effects of Boride Orientation and Si Content on High-Temperature Oxidation Resistance of Directionally Solidified Fe–B Alloys

In this work, the as-cast directionally solidified (DS) Fe–B alloys with various Si contents and different boride orientation were designed and fabricated, and the as-cast microstructures and static oxidation behaviors of the DS Fe–B alloys were investigated extensively. The as-cast microstructure of the DS Fe–B alloys consists of the well-oriented Fe₂B columnar grains and α-Fe, which are strongly refined by Si addition. The oxidation interface of the scales in the DS Fe–B alloy with 3.50 wt.% Si demonstrates an obvious saw-tooth shaped structure and is embedded into the alternating distributed columnar layer structures of the DS Fe–B alloy with oriented Fe₂B and α-Fe matrix, which is beneficial to improve the anti-peeling performance of the oxide film compared with lower amounts of Si addition in DS Fe–B alloys with oriented Fe₂B [002] orientation parallel to the oxidation direction (i.e., oxidation diffusion direction, labeled as Fe₂B_// sample). In the DS Fe–B alloys with oriented Fe₂B [002] orientation vertical to the oxidation direction (i.e., labeled as Fe₂B_⊥ sample), due to the blocking and barrier effect of laminated-structure boride, Si is mainly enriched in the lower part of the oxide film to form a dense SiO₂ thin layer adhered to layered boride. As a result, the internal SiO₂ thin layer plays an obstructed and shielded role in oxidation of the substrate, which hinders the further internal diffusion of oxygen ions and improves the anti-oxidation performance of the Fe₂B_⊥ sample, making the average anti-oxidation performance better than that of the Fe₂B_// sample.     

Effect of Ball Burnishing Pressure on Surface Roughness by Low Plasticity Burnishing Inconel 718 Pre-Turned Surface

The low plasticity burnished surface roughness is significantly affected by the low plasticity burnishing (LPB) parameters. This research proposed the analytical prediction model to predict the LPBed surface roughness and optimal LPB pressure based on Hertz contact mechanics and the slip-line field theory. In this study, the surface formatted process was divided into the smoothing stage (SS) and the indentation stage (IS). The smoothing mechanism of SS and the deterioration mechanism of IS were analyzed theoretically. The analytical prediction model for the LPBed surface roughness was proposed based on Hertz contact mechanics and slip-line field theory. The proposed analytical prediction model was validated by the LPBed surface roughness of AISI 1042, and the error of the analytically predicted results was less than 13.3%. After validation, the proposed model was applied to predict the LPBed surface roughness of Inconel 718. The single-factor experiments were conducted. The error between the proposed model prediction results and experimental results was less than 7% for the LPBed surface roughness of Inconel 718. The optimal LPB pressure interval was calculated to be [12.2 MPa, 17.5 MPa], corresponding to the experimental one as [12 MPa, 18 MPa]. It indicated that the proposed model could accurately predict the LPBed surface roughness and conduct the LPB processing.     

A Study on the Preparation and Cavitation Erosion Mechanism of Polyether Polyurethane Coating

Polyurethane elastomers are anticipated to be applied in the field of cavitation erosion (CE) resistance, but their protection and damage mechanisms are not clear, which greatly restricts their further development. In this article, five polyether polyurethanes (PU_x) with different crosslinking densities were prepared. Their mechanical properties, thermal properties, water absorption, surface morphology and chemical structure before and after CE tests were compared with ESEM, OM, TG-DSC, FTIR and XPS in detail. The results showed that with an increase in crosslinking density, the tensile strength of PU_x increased first and then decreased, elongation at break and water absorption reduced gradually and thermal decomposition temperature and adhesion strength increased steadily. During the CE process, cavitation load aggravated the degree of microphase separation and made brittle hard segments concentrate on the coating surface; meanwhile, cavitation heat accelerated hydrolysis, pyrolysis, oxidation and the fracture of molecular chains. As a result, the mechano-thermal coupling intensified the formation and propagation of fatigue cracks, which should be the fundamental reason for the CE damage of polyurethane elastomer. PU_0.4 exhibited the best CE resistance among the five coatings thanks to its good comprehensive properties and may find potential applications on the surface of hydraulic components.     

Investigation of the Neutralizing Behaviors of Cement-Based Materials Using a New pH Indicator Formulated from February Orchid Petals

Investigation of the neutralizing behavior of concrete is essential, as it can help reveal the durability properties of concrete structures. In this paper, anthocyanin extracted from February orchid (F. orchid) petals was used to characterize the neutralized (carbonated, leached, and sulfate-attacked) regions of cement-based materials. The durability of F. orchid indicator was evaluated through comparison between discoloring behaviors of fresh and aged F. orchid indicators, and the capability of the new indicator in neutralization characterization was then verified by combining indicator (phenolphthalein, malachite green, indigo carmine, or thymolphthalein) spray, X-ray computed tomography (CT), and the X-ray attenuation method (XRAM). The result in the present study showed that, with a lower color intensity as compared to phenolphthalein/thymolphthalein, F. orchid indicator was less preferable in studying carbonation but a better choice in characterizing leaching and sulfate attack of cement-based materials. In addition, a sharp carbonation front was revealed in the present study, suggesting that the carbonation process in this study was controlled mainly by diffusion. For leaching and sulfate attack, the broader fronts revealed suggested that both processes were co-controlled by diffusion and reaction. The current work serves as a ‘leap’ toward the application of natural pigments in analyzing the durability of concrete structures.     

The Damage Performance of Uncarbonated Limestone Cement Pastes Partially Exposed to Na2SO4 Solution

Pore structure and composition of cement paste are the main two factors in controlling the sulfate attack on concrete, but the influence of carbonization on pore structure and composition is often ignored in sulfate attack. Therefore, will the damage performance of concrete partially exposed to sulfate solution be different avoiding the alterations of pore structure and composition due to carbonation? In this paper, the cement pastes were partially immersed in 5 wt. % sodium sulfate solution, with N₂ as protective gas to avoid carbonation (20 ± 1°C, RH 65 ± 5%). Pore structures of cements were changed by introducing different contents of limestone powders (0 wt. %, 10 wt. %, 20 wt. %, and 30 wt. %) into cement pastes. The damage performance of the specimens was studied by ¹H NMR, XRD and SEM. The results showed that the immersion zone of pure cement paste under N₂ atmosphere remained intact while serious damage occurred in the evaporation zone. However, the damage of cement + limestone powders pastes appeared in the immersion zone rather than in the evaporation zone and cement pastes containing more limestone were more severely damaged. Compositional analysis suggested that the damage of the evaporation zone or the immersion zone was solely caused by chemical attack where substantial amount of gypsums and ettringites were filled in the pore volumes. Introduction of limestone powders led to the increase of the pore sizes and porosity of cement pastes, causing the damage occurred in the immersion zone not in the evaporation zone.     

A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants.