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Abstract Lenvatinib, a multitarget kinase inhibitor, has been proven to be effective in the treatment of advanced hepatocellular carcinoma. It has been previously demonstrated that tumour associated macrophages (TAMs) in tumour tissues can promote HCC growth, invasion and metastasis. Furthermore, lenvatinib has certain immunomodulatory effects on the treatment of HCC. However, the role of lenvatinib in macrophage polarization during HCC treatment has not been fully explored. In this study, we used a variety of experimental methods both in vitro and in vivo to investigate the effect of lenvatinib on TAMs during HCC progression. This study is the first to show that lenvatinib can alter macrophage polarization in both humans and mice. Moreover, macrophages treated with lenvatinib in vitro displayed enhanced classically activated macrophages (M1) activity and suppressed liver cancer cell proliferation, invasion, and migration. Furthermore, during the progression of M1 macrophage polarization induced by lenvatinib, STAT-1 was the main target transcription factor, and inhibiting STAT-1 activity reversed the effect of lenvatinib. Overall, the present study provides a theoretical basis for the immunomodulatory function of lenvatinib in the treatment of HCC.

An enclosed microgroove is a vital surface microstructure that is difficult to prepare on the surfaces of difficult-to-machine electrically conductive materials using conventional methods. Electrical discharge machining (EDM) is suitable for this task. It is obtained primarily through layer-by-layer scanning EDM with micro-column electrodes or reciprocating EDM with foil electrodes. However, owing to the small cross-sectional size of the electrodes, a stable machining process is challenging to achieve, which seriously reduces the machining efficiency. To solve these problems, this study proposed ultrasonic vibration-assisted EDM using a laminated electrode possessed strong anti-interference properties for enclosed microgrooves. The effects of ultrasonic vibration on the EDM of microgrooves with single foil and laminated electrodes were investigated. The results show that ultrasonic vibration could improve the machining efficiency of the two types of electrodes and significantly improve the profile quality of the microgrooves prepared using laminated electrodes. When the amplitude was 3 μm and the frequency was 30 kHz, the bottom sidewall corner radius of microgrooves machined by brass foils in laminated electrodes was 28 μm, the width, depth, and roughness of microgrooves machined by copper foils in laminated electrodes were approximately 78 μm, 229 μm and 0.7 μm, the material removal rate was 0.0072 mm3/min. Based on the optimized parameters, inverted “convex” microgrooves with fine consistency were successfully prepared using laminated electrodes on Ti–6Al–4V alloy surfaces. The machining time was reduced by 40% for each microgroove compared with using the single foil electrode. This study provides a new method for preparing complex microgrooves.

Electrode wear during electrical discharge machining (EDM) is inevitable, and tool electrodes of different materials exhibit different wear rates. Unlike a single-material tool electrode, for a laminated electrode consisting of various material foils (LE-VMF), the components suffer from significantly different amounts of wear and also influence each other in EDM, however, the form and cause of the wear are not clear. Thus, the LE-VMFs including symmetric and asymmetric LE-VMFs were prepared and used in EDM in this paper. The wear of foils in LE-VMFs and their mutual influence during the EDM process were investigated through experiments. The wear forms of a single foil electrode and a foil of the same material in the LE-VMF were also compared. The experimental results show that copper foil with a lower wear rate had a protective effect on an adjacent brass foil with a larger wear rate in the LE-VMF, while the protective effect of the brass foil in the symmetric LE-VMF was larger than that in the asymmetric LE-VMF. The closer the distance from the copper foil, the stronger was the protection effect and the smaller was the wear. In addition, the working surface of the brass foil in the LE-VMF did not show any concavity-like wear in the middle region of its thickness after EDM, as was the case for the single brass foil electrode, even if the thickness of the brass foil was greater than 150 μm.

Abstract Severe air pollution poses a significant threat to public safety and human health. Predicting future air quality conditions is crucial for implementing pollution control measures and guiding residents' activity choices. However, traditional single-module machine learning models suffer from long training times and low prediction accuracy. To improve the accuracy of air quality forecasting, this paper proposes a ISSA–LSTM model-based approach for predicting the air quality index (AQI). The model consists of three main components: random forest (RF) and mRMR, improved sparrow search algorithm (ISSA), and long short-term memory network (LSTM). Firstly, RF–mRMR is used to select the influential variables affecting AQI, thereby enhancing the model's performance. Next, ISSA algorithm is employed to optimize the hyperparameters of LSTM, further improving the model’s performance. Finally, LSTM model is utilized to predict AQI concentrations. Through comparative experiments, it is demonstrated that the ISSA–LSTM model outperforms other models in terms of RMSE and R2, exhibiting higher prediction accuracy. The model's predictive performance is validated across different time steps, demonstrating minimal prediction errors. Therefore, the ISSA–LSTM model is a viable and effective approach for accurately predicting AQI.

Objective: Our objective is to assess whether the outcome of intrahepatic unresectable or ablative hepatocellular carcinoma (HCC) could be improved by supplemental transarterial chemoembolization (TACE) following initial treatment of TACE with 3-dimensional conformal radiotherapy (3DCRT), compared to TACE followed by 3DCRT alone. Methods: We retrospectively analyzed intrahepatic unresectable or ablative HCC patients who underwent TACE, followed by 3DCRT with or without additional TACE, from June 2010 to December 2016 at our institution. Survival was assessed using the Kaplan-Meier method and compared with the log-rank test. Cox regression analyses were used to identify factors that influenced prognosis. Toxicity profiles were evaluated using CTCAE 4.0. Results: 27 patients received TACE with 3DCRT (TR group) and 11 received additional TACE following TACE and 3DCRT (sandwich group), respectively. The median intrahepatic progression-free survival (IPFS), progression-free survival (PFS), and overall survival (OS) in the TR group and sandwich group were 5.4 months vs. 17 months (P = 0.018), 5.4 months vs. 17 months (P = 0.008), and 13.5 months vs. 29.2 months (P = 0.011), respectively. Multivariate Cox regression demonstrated that TACE followed by radiotherapy alone had a shorter IPFS (HR: 2.516, 95% CI (1.136-5.570), P = 0.023) and PFS (HR: 2.637, 95% CI (1.182-5.880), P = 0.018) compared with the sandwich treatment. Hepatitis B virus reactivation occurred in 1 patient in the sandwich group. Myleosuppresion was considered a grade 3/4 adverse event. Conclusion: Unresectable or ablative HCC patients possibly benefit from the combination of TACE and 3DCRT followed by additional TACE therapy, compared with TACE followed by 3DCRT alone.

Abstract Background Hepatic arterioportal shunt (A-P shunt) is defined as the direct blood flow established between hepatic artery and portal venous system; it is frequently observed in patients with hepatocellular carcinoma (HCC). Clinically, it is important to diagnose HCC associated A-P shunts, as it may impact the treatment strategy of the patients. In the present study, we described the imaging findings of the HCC associated A-P shunts and discussed the treatments strategy of such patients. From the findings, we also discussed the potential cause of A-P shunts. Methods Clinical data of HCC patients (n = 560), admitted to the hospital between April 2012 to April 2014, were reviewed. Hepatic angiography was used to examine the presence of A-P shunts. Of the 137 patients with A-P shunts, grading of the A-P shunts was performed, and statistical analysis of the different grades of A-P shunts and clinical characteristics was performed. Results The hepatic angiography confirmed that 99 patients had typical A-P shunts (Grade 1–3), and 38 patients had atypical A-P shunts. Embolization was the main strategy used to treat A-P shunts, in which liquid embolic agents appeared to provide a better treatment outcome. The correlation analysis showed that the grading of portal vein tumor thrombus was significantly associated with the grading of A-P shunt (p =

In this paper, the model-based fuzzy control application for double-layer operation systems with uncertainty is addressed. Due to the multiple-time scales of complex industrial systems, as well as the inborn uncertainties of the system, the challenge of feedback control is presented. A new approach based on a class of fuzzy models with uncertainty fulfilling the condition of sector bound for the operation process system is proposed. First, a fuzzy model of the system is considered in terms of the system's described dynamical characteristics, and the PI fuzzy controller is then employed for the model, which will ensure controlled plant tracking set-points. Second, with different sampling rates, a dual-layer model combining PI fuzzy controller and dynamical fuzzy output feedback controller are presented. Third, the S-procedure is applied to derive the feedback controller, which can simultaneously guarantee the mean value of steady-state error between the realistic and target operational index is zero and the stability of the dual closed-loop control system is established. Finally, significant simulations have been executed to show the effectiveness of the proposed approach.

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer, and it is the second most common cancer-related mortality globally. The prognostic value of high mobility group box 1 (HMGB1) remains controversial. The purpose of this study is to conduct a meta-analysis and literature review to evaluate the association of HMGB1 expression with the prognosis of patients with HCC.MethodsA detailed literature search was made in Medline, Google Scholar and others for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, Hazard Ratio (HR) and mean difference with corresponding confidence intervals (CIs) were calculated and summarized respectively.Results10 relevant articles were included for this meta-analysis study. HMGB1 mRNA levels in HCC were significantly higher than those in normal (pConclusionsThe results of this meta-analysis suggest that HMGB1 mRNA and protein tissue levels in the patients with HCC are significantly higher than those in para-tumor and normal liver tissues respectively. Tissue HMGB1 overexpression is a potential biomarker for HCC diagnosis, and it is significantly associated with the prognosis of patients with HCC.

Hepatocellular carcinoma (HCC) is one of the most deadly tumors. Transarterial chemoembolization (TACE) is effective for unresectable HCC. In recent years, miRNAs have been proposed as novel diagnostic and prognostic tools for HCC. This study aimed to identify whether microRNAs (miRNAs) can serve as biomarkers to reliably predict outcome before HCC patients are treated with TACE.Eleven miRNAs (miR-, miR-19a, miR-101-3p, miR-199a-5p, miR-200a, miR-21, miR-214, miR-221, miR-222, miR-223 and miR-, -5p) were quantified by quantitative real-time PCR (qRT-PCR) in 136 HCC patients' serum before they received TACE therapy. Univariate and multivariate analysis were used to identify the prognostic value of clinical parameters and miRNAs. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prediction potency.The levels of some miRNAs were dramatically associated with clinicopathologic features regarding Child-Puge class, AFP, tumor size and satellite nodules. Univariate analysis revealed that miR-200a, miR-21, miR-122 and miR-224-5p were significantly associated with patients' survival. Multivariate analysis demonstrated that AFP, satellite nodules and miR-200a were the independent prognostic factors associated with survival in this cohort (p = 0.000, 0.001, 0.000, respectively). The probability of the prognostic accuracy of miR-200a was 81.64% (74.47% specificity and 88.76% sensitivity), which was higher than the classifier established by combination of AFP and satellite nodules (76.87% probability, 70.21% specificity and 69.66% sensitivity). Furthermore, the combination of AFP, satellite nodules and miR-200a demonstrated as a classifier for HCC prognosis, yielding a ROC curve area of 88.19% (93.62% specificity and 68.54% sensitivity).Our study indicated that serum miR-200a may prognosticate disease outcome in HCC patients with TACE therapy. Therefore, miR-200a can potentially guide individualized treatment for HCC patients with a high risk of TACE treatment failures.