Significant association between high neutrophil-lymphocyte ratio and poor prognosis in patients with hepatocellular carcinoma: a systematic review and meta-analysis

ObjectiveWhether neutrophil-lymphocyte ratio (NLR) is an applicative predictor of poor prognosis in patients with hepatocellular carcinoma (HCC) remains controversial. In response to the current conflicting data, this meta-analysis was conducted to gain a comprehensive and systematic understanding of prognostic value of NLR in HCC.MethodsSeveral English databases, including PubMed, EMBASE, and the Cochrane Library, with an update date of February 25, 2023, were systematically searched. We set the inclusion criteria to include randomized controlled trial (RCT) studies that reported the prognostic value of serum NLR levels in patients with HCC receiving treatment. Both the combined ratio (OR) and the diagnosis ratio (DOR) were used to assess the prognostic performance of NLR. Additionally, we completed the risk of bias assessment by Cochrane Risk of Bias Assessment Tool.ResultsThis meta-analysis ultimately included 16 studies with a total of 4654 patients with HCC. The results showed that high baseline NLR was significantly associated with poor prognosis or recurrence of HCC. The sensitivity of 0.67 (95% confidence interval [CI]. 0.59-0.73); specificity of 0.723 (95% CI: 0.64-0.78) and DOR of 5.0 (95% CI: 4.0-7.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLHR) were calculated with the results of 2.4 (95% CI: 1.9-3.0) and 0.46 (95% CI: 0.39-0.56), respectively. In addition, area under the curve (AUC) of the summary receiver operating characteristic (SROC) reflecting prognostic accuracy was calculated to be 0.75 (95% CI: 0.71-0.78). The results of subgroup analysis suggested that high NLR was an effective predictive factor of poor prognosis in HCC in mainland China as well as in the northern region.ConclusionOur findings suggest that high baseline NLR is an excellent predictor of poor prognosis or relapse in patients with HCC, especially those from high-incidence East Asian populations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023440640

Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL-5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL

The Fip1-like1 (FIP1L1)–platelet-derived growth factor receptor alpha (PDGFRA) (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5 cytokine participation. In this study, we investigate the mechanism of F/P in collaboration with IL-5 in CEL. The results showed that Lyn, a key effector in the IL-5-motivated eosinophil production, is extensively activated in F/P-positive CEL cells. Lyn can associate and phosphorylate IL-5 receptor α (IL-5RA) in F/P-positive cells. Moreover, the activation of Lyn and IL-5R kinase were strengthened when the cells were stimulated by IL-5. Lyn inhibition in F/P-positive CEL cells attenuated cellular proliferation, induced apoptosis, and blocked cell migration and major basic protein (MBP) release. We identified the FIP1L1-PDGFRA/JAK2/Lyn/Akt complex in the F/P-expressing cells which can be disrupted by dual inhibition of JAK2 and Lyn, repressing cell proliferation in both EOL-1(F/P-positive human eosinophilic cell line) and imatinib-resistance (IR) cells. Altogether, our data demonstrate that Lyn is a vital downstream kinase activated by F/P converged with IL-5 signals in CEL cells. Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL

Nonlinear dynamic seismic response of container crane based on contact friction theory

To evaluate the dynamic behavior of a container crane under seismic loads accurately, the contact state between the wheels and the rails or the ground that significantly affect the seismic response of the structure must be considered elaborately. This paper proposes a modeling method based on the theory of contact and friction for simulating the nonlinear seismic response of large and flexible structure for a jumbo movable container crane, including the contact problem regarding the wheels attached to the bottom of its legs and the rails on which they ride. These models are used to perform extensive dynamic time-history analysis in order to find out their nonlinear dynamic behavior under various excitation modes. It is found that the presented numerical modeling method simulates the nonlinear seismic response of a container crane quite well. Notably, it can verify and expand our understanding of the seismic behaviors by evaluating response performance for other large seaport cranes

Interval optimization design of a submersible surface ship form considering the uncertainty of surrogate model

The integrated design of the ship form is a key issue in the design of submersible surface ship (SSS). In the simulation-based design (SBD) framework, lack of sample data leads to uncertainty in the surrogate model. In this paper, first, a hull cross-section shape modification technology, the self-fusion method, was used to change the ship form, and a fourth-order response surface model was introduced to establish surrogate model of hydrodynamic performance. Second, total resistance in the surface condition and one at a diving depth of 0.48 m were selected as the optimization targets. Third, an automated computing platform was developed to integrate the modules to improve computing efficiency and accuracy. Finally, to explore the adaptability of the ship form scheme, the interval optimization analysis method was introduced into uncertainty optimization. Among them, the interval variable was the surrogate model accuracy, and the targets were the minimum median and the minimum radius of the weighted resistance of cross-domain cases. A two-layer nested optimization system was chosen. Results show that resistance of the optimal SSS was reduced. The interval optimization results were compared with the deterministic optimization results, and thefeasibility of hull shape interval optimization was verified

Circular RNAs in cancer: an emerging key player

Abstract Circular RNAs (circRNAs) are a class of endogendous RNAs that form a covalently closed continuous loop and exist extensively in mammalian cells. Majority of circRNAs are conserved across species and often show tissue/developmental stage-specific expression. CircRNAs were first thought to be the result of splicing error; however, subsequent research shows that circRNAs can function as microRNA (miRNA) sponges and regulate splicing and transcription. Emerging evidence shows that circRNAs possess closely associated with human diseases, especially cancers, and may serve as better biomarkers. After miRNA and long noncoding RNA (lncRNA), circRNAs are becoming a new hotspot in the field of RNA of cancer. Here, we review biogenesis and metabolism of circRNAs, their functions, and potential roles in cancer

Vibration source model estimation and state specificity perception of a rotor structure

Rotor structures in abnormal states will create non-stationary vibration sources, these non-stationary features are often ignored by traditional signal processing algorithms, thereby the determination of rotor running states is affected. A new state specificity perception method based on kernel density function estimation combined with higher moments feature extraction and multi-class support vector machine is proposed. Firstly, for rotors with non-stationary vibration source, kernel density estimation algorithm is used to estimate the probability density model, which fully considers band broadening features of non-stationary signals. Then higher order moments of non-stationary vibration source model are calculated, the values are assembled to state mark vectors. Finally, the multi-class support vector machine is used to classify the state mark vectors. Three types of abnormal states are set on cascade rotor system for experiments, acceleration data is collected and the state specificity perception process is carried out. All abnormal states are identified successfully. High accuracy proves the effectiveness of Kernel Density Estimation-Support Vector Machine (KDE-SVM) method. The proposed specificity extraction and perception method provides new ideas for running structure condition monitoring

Circadian gene ARNTL initiates circGUCY1A2 transcription to suppress non-small cell lung cancer progression via miR-200c-3p/PTEN signaling

Abstract Background As a subclass of endogenous stable noncoding RNAs, circular RNAs are beginning to be appreciated for their potential as tumor therapeutics. However, the functions and mechanisms by which circRNAs exert protective functions in non-small cell lung cancer (NSCLC) remain largely elusive. Methods The prognostic role of circGUCY1A2 was explored in lung adenocarcinoma specimens. The overexpressed and knockdown plasmids were used to evaluate the effect of circGUCY1A2 on NSCLC cell proliferation and apoptosis efficacy. Luciferase reporter system is used to prove that circGUCY1A2 could bind to miRNA. Chip-PCR was used to prove that circGUCY1A2 could be initiated by transcription factors ARNTL. Subcutaneous tumorigenicity grafts models were established to validate findings in vivo. Results The expression of circGUCY1A2 were significantly reduced (P < 0.001) and negatively correlated with tumor size (P < 0.05) in non-small cell lung cancer (NSCLC). CircGUCY1A2 upregulation promoted apoptosis and inhibits cell proliferation and growth of subcutaneous tumorigenicity grafts in nude mice (P < 0.01). In addition, intra-tumor injection of pLCDH-circGUCY1A2 inhibited tumor growth in patient-derived NSCLC xenograft models (PDX). Mechanism studies showed that circGUCY1A2 could act as a sponge to competitively bind miR-200c-3p, promote PTEN expression, and thereby inhibit PI3K/AKT pathway. In addition, we found that the circadian gene ARNTL, which was reduced in NSCLC and prolonged the overall survival of patients, could bind to the promoter of circGUCY1A2, thereby increasing its expression. Conclusions This study is an original demonstration that ARNTL can inhibit the development of lung adenocarcinoma through the circGUCY1A2/miR-200c-3p/PTEN axis, and this finding provides potential targets and therapeutic approaches for the treatment of lung adenocarcinoma