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Abstract Background The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. Methods Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. Results A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. Conclusions NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Abstract Background and aims Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. Methods Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. Results Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765–0.894) and 0.729 (95%CI: 0.706–0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. Conclusion Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P < .05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P = .001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P = .016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival.

PurposeWe evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.Materials and methodsThe Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients.ResultsIn the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%).ConclusionThe Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

Background & aimsThe long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy.MethodsPatients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS).Result389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002).ConclusionMS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.

Abstract Background Patients with lung adenocarcinoma (LUAD) have high mortality rate and poor prognosis. The LUAD cells display increased aerobic glycolysis, which generates energy required for their survival and proliferation. Deregulation of Wnt/β-catenin signaling pathway induces the metabolism switching and oncogenesis in tumor cells. RING finger protein 115 (RNF115) is an E3 ligase for ubiquitin-mediated degradation. Although the oncogenic functions of RNF115 have been revealed in breast tumor cells, the effect of RNF115 on lung cancer is still not clear. Methods RNF115 expression and its correlation with the features of LUAD patients were analyzed by using public database and our own cohort. The functions of RNF115 in proliferation and energy metabolism in LUAD cells were explored by downregulating or upregulating RNF115 expression. Results We demonstrated that RNF115 was overexpressed in LUAD tissues and its expression was positively correlated with the poor overall survival of LUAD patients. Moreover, RNF115 overexpression inhibited LUAD cell apoptosis and promoted cellular proliferation and metabolism in LUAD cells. On the contrary, RNF115 knockdown displayed reverse effects. Furthermore, the underlying mechanism of the biological function of RNF115 in LUAD was through regulating Wnt/β-catenin pathway via ubiquitination of adenomatous polyposis coli (APC). Conclusion The current study reveals a close association between RNF115 expression and prognostic conditions in LUAD patients and the oncogenic roles of RNF115 in LUAD at the first time. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for lung cancer in future.

Chromia-forming ferritic stainless steel (FSS) is a highly promising interconnect material for application in solid oxide fuel cells. In this study, initial oxidation of chromium oxides was performed at 500–800 °C to understand the evolution of materials at an early stage. The structural variations in oxide scales were analyzed through scanning electron microscopy, energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), X-ray diffractometry (XRD), laser confocal microscopy (LSCM), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Surface electrochemical properties were investigated through electrochemical impedance spectroscopy to understand how the heat treatment temperature affected surface impedance. Treatment temperatures higher than 700 °C facilitate the diffusion of Cr and Mn, thus allowing ferritic spinels to form on the surface and leading to high electrical conductivity.

Traditional intelligent product design usually focuses on functional design, aiming to generate appropriate structures that would provide required functions. Design specifications are mainly formulized into technical descriptions or values that are related to certain functional or usability requirements. In today’s global market, to in-crease user satisfaction, the appearance design of a product become vital for users to make purchasing decisions. This is particularly true of today’s consumer products such as mobile phones, digital cameras, and other electronic products. In intelligent product appearance design, design specifications are merely described as basic geometric dimensions and types of surface materials. Additionally, the aesthetic considerations and emotional needs of product appearance are seldom discussed when establishing design specifications for product appearance design. In this regard, the objective of this study is to propose a design specification representation framework for intelligent product appearance design considering both emotional and aesthetic aspects. The framework be-gins to investigate user needs by acquiring user aesthetic experience. Based on the notion of aesthetic experience, a detailed representation model of appearance design specifications is provided for satisfying user emotional and aesthetic needs. Finally, a case study of the appearance design of digital cameras is provided to demonstrate the acquisition of user needs and establishment of design specifications based on the proposed framework.

With the prosperity of laser powder bed fusion (LPBF) technology, post-processing tends to be increasingly attractive in further improving the performance of the LPBFed parts. In this study, post-heat treatment and electroless plating were performed on the LPBFed 316L stainless steel to investigate the evolution of surface topography, mechanical property and corrosion behaviour. The results show that the as-built part features melt tracks and fine cellular substructures, which presents higher deformation resistance than the cast and recrystallized counterparts. The uniform amorphous Ni-P coating can significantly increase microhardness of as-built 316L stainless steel from ~300 to ~800 HV. In addition, the as-built parts with/without coatings have better corrosion resistance than the corresponding cast ones, which can be further improved through 450°C annealing. Moreover, the coatings can also prevent the localised corrosion effectively. Therefore, this study provides available post-processing methods for further improve the performance of LPBFed 316L stainless steel. [ABSTRACT FROM AUTHOR]

NGCs are considered as an alternative treatment method for treating peripheral nerve injuries in place of nerve autografts. Biomimicry, conductivity, and biodegradability are the properties expected of an ideal NGC. PCL/PAA NGCs with three different concentrations of PAA (2.5, 5 and 7.5%) were fabricated using EHD-jet 3D printing. The mechanical properties of the PCL/PAA NGCs mimic the native human nerve properties (ultimate tensile strength of 6.5 to 11.7 MPa) and the conductivity match that of the amphibian motor nerve fiber myelin sheath (10−6 S/cm). The in vitro degradation studies reveal that they are biodegradable and injury/site-specific biodegradability can be obtained by tuning the PCL/PAA concentration ratio. In addition, PAA being a polyanionic polymer has the potential to act as a cation-exchanger, mimicking the functions of the nerve cortical gel layer, thereby influencing the electrophysiological phenomena called nerve excitation and conduction. Neural differentiation studies with PC12 cells assessed by the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunocytochemistry showed enhanced gene expression with the presence of PAA. Our results suggest that the EHD-jet 3D printed porous conductive PCL/PAA NGCs has the potential to be used in the treatment of peripheral nerve injuries. Keywords: 3D printing, Tissue engineering scaffolds, Peripheral nerve injury, Nerve guide conduits, Electrohydrodynamic jet, Conductive scaffolds

Overlapping melting trajectories and partially-melted powders result in poor surface morphology and high surface roughness values (Ra = ~13.34 μm) of selective laser melted (SLMed) Ti6Al4V alloy. Secondary processing of SLMed components is thus an essential finishing operation to produce functional SLMed parts in precision engineering. This paper investigates the effects of laser scanning strategies (0°, 67.5° and 90° laser scanning schemes) and machining surfaces (top and front surfaces) on the machining performance of SLMed Ti6Al4V alloy in milling, compared with that of annealed ASTM B265 Ti6Al4V alloy. High degree of anisotropy of SLMed Ti6Al4V alloy is reflected in cutting force, surface morphology and surface roughness on different machining surfaces. The machining anisotropy is dominated by the anisotropy of microstructure and mechanical properties of SLMed Ti6Al4V alloy, where the anisotropy weakens following the sequence of 0°, 90° and 67.5° SLMed samples. It is verified that high cutting speed can improve machining anisotropy features of SLMed titanium alloy. The chip shape of SLMed Ti6Al4V alloy is a typical conical spiral chip, and the bending degree and length of chips produced by SLMed Ti6Al4V alloy are larger than those produced by annealed Ti6Al4V alloy.

This paper aims to improve the surface quality of 316L stainless steel parts manufactured by selective laser melting (SLM) using dry mechanical-electrochemical polishing (DMECP). DMECP is an advanced surface finishing method combining the advantages of both mechanical and electrochemical polishing techniques in a more environmentally friendly manner. In this paper, the SLM process-related defects causing poor surface quality are analysed first. The material removal mechanism of DMECP is investigated to continuously remove the oxide layers formed during polishing. Surface morphology and roughness evolution under different polishing conditions are characterised. The top surface roughness can be reduced by over 91% from 8.72 μm to 0.75 μm compared to side surface by over 93% from 12.10 to 0.80 μm. The material removal on the top surface is more efficient than that on the side surface under the same polishing condition. The secondary defects formed during polishing can be removed using mechanical polishing mode. The chemical element composition of the polished surface exhibits almost identical content to the initial 316L powders. Compared with the initial dark and rough surfaces, the results validate the capability of DMECP as an effective tool to improve the SLM surface quality and achieve a mirror finish.

Conductivity is a desirable property of an ideal nerve guide conduit (NGC) that is being considered for peripheral nerve regeneration. Most of the conductive polymers reported in use for fabrication of tissue engineering scaffolds such as polypyrrole (PPy), polyaniline, polythiophene, and poly(3,4-ethylenedioxythiophene) are non-biodegradable and possess weak mechanical properties to be fabricated into 3D structures. In this study, a biodegradable and conductive block copolymer of PPy and Polycaprolactone (PPy-b-PCL) was used to fabricate 3D porous NGCs using a novel electrohydrodynamic jet 3D printing process which offers superior control over fiber diameter, pore size, porosity, and fiber alignment. PCL/PPy scaffolds with three different concentrations of PPy-b-PCL (0.5, 1, and 2% v/v) were fabricated as a mesh (pore size 125 ± 15 μm) and the effect of incorporation of PPy-b-PCL on mechanical properties, biodegradability, and conductivity of the NGCs were studied. The mechanical properties of the scaffolds decreased with the addition of PPy-b-PCL which aided the ability to fabricate softer scaffolds that are closer to the properties of the native human peripheral nerve. With increasing concentrations of PPy-b-PCL, the scaffolds displayed a marked increase in conductivity (ranging from 0.28 to 1.15 mS/cm depending on concentration of PPy). Human embryonic stem cell-derived neural crest stem cells (hESC-NCSCs) were used to investigate the impact of PPy-b-PCL based conductive scaffolds on the growth and differentiation to peripheral neuronal cells. The hESC-NCSCs were able to attach and differentiate to peripheral neurons on PCL and PCL/PPy scaffolds, in particular the PCL/PPy (1% v/v) scaffolds supported higher growth of neural cells and a stronger maturation of hESC-NCSCs to peripheral neuronal cells. Overall, these results suggest that PPy-based conductive scaffolds have potential clinical value as cell-free or cell-laden NGCs for peripheral neuronal regeneration.

Bioelectricity has been a fundamental property of all living organisms. With electrical stimulation, living cells can interact with their microenvironments, which makes electrical stimulation highly beneficial for various biomedical applications. However, traditional electrical stimulation mainly relies on bulky and complex equipment, which may not be ideal due to the restriction of movement, limited battery lifetime, uncomfortable wearing, and potential unfriendly to the environment. The advent of triboelectric nanogenerators (TENGs) has helped to resolve the existing limitations. TENGs are effective energy harvesting systems that use a mix of triboelectrification and electrostatic induction to create electrical energy from kinetic energy. TENGs deliver self-powered electrical stimulation to bone cells for functional regulation or bone regeneration, serve as sensors to detect biological signals or movements, or act as a power source for other biomedical devices. TENGs can be employed in various applications, including enhancing bone regeneration, providing sensing function, slowing bone aging, and curing implant-related infections. The recent applications of TENGs in bone tissue engineering are reviewed, and the drawbacks of the TENGs are discussed. Finally, the existing challenges and future roadmap for developing TENGs are presented. [ABSTRACT FROM AUTHOR]

The prevalence of peripheral nerve injuries resulting in loss of motor function, sensory function, or both, is on the rise. Artificial Nerve Guide Conduits (NGCs) are considered an effective alternative treatment for autologous nerve grafts, which is the current gold-standard for treating peripheral nerve injuries. In this study, Polycaprolactone-based three-dimensional porous NGCs are fabricated using Electrohydrodynamic jet 3D printing (EHD-jetting) for the first time. The main advantage of this technique is that all the scaffold properties, namely fibre diameter, pore size, porosity, and fibre alignment, can be controlled by tuning the process parameters. In addition, EHD-jetting has the advantages of customizability, repeatability, and scalability. Scaffolds with five different pore sizes (125 to 550 μm) and porosities (65 to 88%) are fabricated and the effect of pore size on the mechanical properties is evaluated. In vitro degradation studies are carried out to investigate the degradation profile of the scaffolds and determine the influence of pore size on the degradation rate and mechanical properties at various degradation time points. Scaffolds with a pore size of 125 ± 15 μm meet the requirements of an optimal NGC structure with a porosity greater than 60%, mechanical properties closer to those of the native peripheral nerves, and an optimal degradation rate matching the nerve regeneration rate post-injury. The in vitro neural differentiation studies also corroborate the same results. Cell proliferation was highest in the scaffolds with a pore size of 125 ± 15 μm assessed by the PrestoBlue assay. The Reverse Transcription-Polymerase Chain Reaction (RT-PCR) results involving the three most important genes concerning neural differentiation, namely β3-tubulin, NF-H, and GAP-43, confirm that the scaffolds with a pore size of 125 ± 15 μm have the highest gene expression of all the other pore sizes and also outperform the electrospun Polycaprolactone (PCL) scaffold. The immunocytochemistry results, expressing the two important nerve proteins β3-tubulin and NF200, showed directional alignment of the neurite growth along the fibre direction in EHD-jet 3D printed scaffolds.