Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

An efficient DNAzyme-locked leakless enzyme-free amplification system for alpha-foetoprotein detection in liver cancer and breast cancer.

Alpha-foetoprotein (AFP) is taken as a diagnostic tumor marker for the screening and diagnosis of cancer. Nucleic acid-based isothermal amplification strategies are emerging as a potential technology in early screening and clinical diagnosis of AFP. The leakages between hairpins dramatically increase the background and reduce the sensitivity. Thus, it is necessary to develop some strategies to reduce the leakage for isothermal amplification strategies. A DNAzyme-locked leakless enzyme-free amplification system was developed for AFP detection in liver cancer and breast cancer. AFP could open the apt-hairpin and initiate the catalytic hairpin assembly (CHA) reaction to produce a Y-shaped duplex. Two tails of a Y-shaped duplex cleaved the two kinds of leakless hairpins. Then, the third tail of the Y-shaped duplex catalyzed the second CHA between the cleaved leakless hairpins to recover the fluorescent intensity. The limit of detection reached 5 fg/mL by the two levels of signal amplifications. Importantly, the leakless hairpin design effectively reduced leakage between hairpins and weakened the background. In addition, it also showed a great promising potential for AFP detection in early screening and clinical diagnosis.

CircVIRMA enhances cell malignant behavior by governing the miR-452-5p/CREBRF pathway in cervical cancer.

Our current study aimed to investigate the role and mechanism of circVIRMA in cervical cancer (CC) progression. CircVIRMA, microRNA-452-5p (miR-452-5p) and CREB3 regulatory factor (CREBRF) mRNA levels were examined in CC via quantitative real-time PCR (qRT-PCR). The protein level of CREBRF in CC was checked by Western blot. Cell Counting Kit-8 (CCK-8), colony formation, 5-Ethynyl-2'-deoxyuridine (EdU) staining, cell cycle, flow cytometry and transwell assays were conducted to estimate the effects of circVIRMA on malignant phenotypes of CC tumors. Western blot was used to measure related marker protein levels. The interaction between miR-452-5p and circVIRMA or CREBRF was predicted by bioinformatics analysis and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Xenograft assay was used to assess the effect of circVIRMA on tumor growth in vivo. Immunohistochemistry (IHC) assay was performed to detect Ki-67 expression in tissues of mice. CircVIRMA and CREBRF levels were upregulated, while miR-452-5p was downregulated in CC tissues and cells. CircVIRMA silencing restrained CC cell proliferation, migration and invasion whereas induced apoptosis in vitro. In addition circVIRMA knockdown markedly attenuated xenograft tumor growth in vivo. circVIRMA was an efficient molecular sponge for miR-452-5p, and negatively regulated miR-452-5p expression. circVIRMA regulated CREBRF expression to modulate CC progression via miR-452-5p. MiR-452-5p downregulation reversed the effects of circVIRMA knockdown on CC progression. MiR-452-5p directly targeted CREBRF, and CREBRF overexpression partly restored the impact of miR-452-5p mimics on CC progression. circVIRMA mediated CC progression via regulating miR-452-5p/CREBRF axis, providing a novel therapeutic target for CC treatment.

Correction: Identification of serum prognostic marker miRNAs and construction of microRNA-mRNA networks of esophageal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].

Large rectangular cross-section tunnel undercrossing urban road by micro pipe jacking and joint assembly structure (MPJ & JAS) method in soft soils.

With the continuous construction of urban traffic roads, more and more new roads are cut off by existing roads to form "dead end roads". There is an urgent need for a trenchless method suitable for urban ultra-shallow overburden to build the undercrossing tunnel. To solve this problem, this paper proposed the micro pipe jacking and joint assembly structure (MPJ & JAS) method, which has the characteristics of shallow burial depth, low cost, short construction time, flexible cross-section setting and high space utilization. The MPJ & JAS method construct a large cross-section tunnel through assembling small cross-section elements, quite different from traditional methods. Therefore, this paper designed a CT-shaped integrated joint, the mechanical performance of which was verified and clarified by tensile test. The bending test and finite element (FE) analysis proved the reliability of MPJ & JAS tunnel structure, and confirmed the structure performances such as the failure models, crack behaviors, load-deflection response and stress-strain distribution. Moreover, the influences of the steel plate thickness, concrete strength and shear connector spacing were determined by the FE analysis. On the basis of test results and reasonable assumptions, a theoretical design method considering the influence of the CT-shaped integrated joint was proposed, which can effectively predict the bending strength of the MPJ & JAS tunnel structure with an error of less than 10%. Finally, in view of the characteristics of the MPJ & JAS method, the suitable micro pipe jacking machine, soil reinforcement measure, hydraulic traction construction technology, high-precision guidance system and concrete construction quality detection method based on the phased array ultrasonic imaging technology were developed, supporting the accurate and efficient construction of the MPJ & JAS tunnel.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

Drug-eluting bead transarterial chemoembolization (DEB-TACE) versus conventional transarterial chemoembolization (cTACE) in colorectal liver metastasis: Efficacy, safety, and prognostic factors.

OBJECTIVE: To comparatively evaluate drug-eluting bead transarterial chemoembolization (DEB-TACE) and conventional transarterial chemoembolization (cTACE) for efficacy, safety, and related prognostic factors in the treatment of colorectal liver metastasis (CRLM). MATERIALS AND METHODS: This study retrospectively analyzed 75 patients with CRLM-administered DEB-TACE (n = 36) or cTACE (n = 39) between January 2016 and December 2017. Local control, survival outcome, and complications were compared between the two groups. Univariate and multivariate analyses of prognostic factors affecting progression-free survival (PFS) and overall survival (OS) were performed. RESULTS: The median follow-up in the two groups was 10.5 months (range, 0.5-22). Median PFS and OS in the DEB-TACE group were 10.0 and 13.0 months, respectively, and 6.0 and 8.5 months in the cTACE group, respectively (P = 0.009 and P = 0.008). The 3-, 6-, and 12-month OS rates in the DEB-TACE group were 100.0%, 94.4%, and 55.6%, respectively, and 92.3%, 71.8%, and 35.9% in the cTACE group, respectively. The 3-month OS rate (P = 0.083) showed no significant difference between the two groups, but significant differences were found in the 6- and 12-month OS rates (P = 0.008 and P = 0.030). Univariate and multivariate survival analyses showed that treatment method, tumor size, and tumor number were independent prognostic factors affecting PFS and OS. CONCLUSION: DEB-TACE has advantages over cTACE in prolonging PFS and OS in patients with CRLM. Treatment method, tumor number, and tumor size are important prognostic factors affecting PFS and OS. However, further multicenter and prospective trials are needed to confirm a deeper comparison between DEB-TACE and cTACE in patients with CRLM.