Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).

Probe-based confocal laser endomicroscopy for evaluating high-altitude pulmonary edema in canines.

Background: Real-time assessment of high-altitude pulmonary edema (HAPE) remains a challenge. Probe-based confocal laser microscopy (pCLE) allows a real-time in vivo visualization of the alveoli. This study aimed to develop a new non-invasive method for analyzing microscopic images in a canine model of HAPE using pCLE. Materials and methods: This was a prospective, controlled animal study in adult male beagle dogs randomized to control and HAPE groups. The HAPE group was exposed to a high altitude of 6000 m for 48 h. The blood gas levels, lung morphological changes, infectious factors, and lung wet-to-dry ratio were analyzed in different groups. The pCLE images were described based on the volume air index (VAI), which applies an integral over specific signal intensities. Results: The lung wet-to-dry weight ratio and injury scores in the HAPE group were significantly increased compared with those of the control group. The levels of infectious factors interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 were significantly increased in the HAPE group compared with those in the control group. VAI was significantly decreased in the HAPE group. Conclusion: pCLE is a potential adjudicative bronchoscopic imaging technique for assessing HAPE. VAI may be acquired from quantitative parameters in the analysis of images.

Deletions of singular U1 snRNA gene significantly interfere with transcription and 3'-end mRNA formation.

Small nuclear RNAs (snRNAs) are structural and functional cores of the spliceosome. In metazoan genomes, each snRNA has multiple copies/variants, up to hundreds in mammals. However, the expressions and functions of each copy/variant in one organism have not been systematically studied. Focus on U1 snRNA genes, we investigated all five copies in Drosophila melanogaster using two series of constructed strains. Analyses of transgenic flies that each have a U1 promoter-driven gfp revealed that U1:21D is the major and ubiquitously expressed copy, and the other four copies have specificities in developmental stages and tissues. Mutant strains that each have a precisely deleted copy of U1-gene exhibited various extents of defects in fly morphology or mobility, especially deletion of U1:82Eb. Interestingly, splicing was changed at limited levels in the deletion strains, while large amounts of differentially-expressed genes and alternative polyadenylation events were identified, showing preferences in the down-regulation of genes with 1-2 introns and selection of proximal sites for 3'-end polyadenylation. In vitro assays suggested that Drosophila U1 variants pulled down fewer SmD2 proteins compared to the canonical U1. This study demonstrates that all five U1-genes in Drosophila have physiological functions in development and play regulatory roles in transcription and 3'-end formation.

Regiodivergent and Stereoselective Synthesis of Highly Substituted 1,3-Dienes via Arylative Acyloxy Migration of Propargyl Esters.

We report the first catalyst-controlled regiodivergent method that enables the synthesis of structurally diverse 1,2,3,4-tetrasubstituted conjugated dienes with excellent regio- and stereochemical outcomes from the same set of readily available propargyl esters and diaryliodonium salts. In this diene chemistry, the in situ generated, highly electrophilic aryl-CuIII complex serves not only as a π-Lewis acid catalyst for alkyne activation/acyloxy migration but also as an aryl electrophile equivalent. The competitive arylative 1,2- and 1,3-acyloxy migration patterns are exquisitely dictated by Cu and Au/Cu relay catalyses, respectively, providing a modular and attractive approach to traditionally inaccessible tetrasubstituted 1,3-dienes in a regiodivergent manner. Finally, the synthetic utility of this method is demonstrated by further synthetic derivatization of 1,3-dienes into an array of useful compounds.

Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF-κB and Nrf2/HO-1/GPX4 pathways to reduce inflammation and ferroptosis.

Acute liver failure (ALF) is an inflammation-mediated hepatocyte death process associated with ferroptosis. Avicularin (AL), a Chinese herbal medicine, exerts anti-inflammatory and antioxidative effects. However, the protective effect of AL and the mechanism on ALF have not been reported. Our in vivo results suggest that AL significantly alleviated lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced hepatic pathological injury, liver enzymes, inflammatory cytokines, reactive oxygen species and iron levels and increased the antioxidant enzyme activities (malondialdehyde and glutathione). Our further in vitro experiments demonstrated that AL suppressed inflammatory response in LPS-stimulated RAW 264.7 cells via blocking the toll-like receptor 4 (TLR4)/myeloid differentiation protein-88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. Moreover, AL attenuated ferroptosis in D-GalN-induced HepG2 cells by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway. Therefore, AL can alleviate inflammatory response and ferroptosis in LPS/D-GalN-induced ALF, and its protective effects are associated with blocking TLR4/MyD88/NF-κB pathway and activating Nrf2/HO-1/GPX4 pathway. Moreover, AL is a promising therapeutic option for ALF and should be clinically explored.

Manganese-Catalyzed Redox-Neutral Thiolation of Alkyl Halides with Thioformates.

Transition metal-catalyzed C-S cross-coupling has emerged as an important strategy to furnish thioethers; however, the dominant utilization of noble metal catalysts as well as the construction of challenging C(sp3 )-S bonds by transition metal-catalysis remain highly problematic. Earth-abundant manganese has gathered increasing interest as an attractive catalyst for new reaction development; nevertheless, C(sp3 )-S cross-coupling reaction by manganese catalysis has not been reported. Herein, we disclose a highly efficient manganese-catalyzed redox-neutral thiolation of a broad range of alkyl halides with thioformates as practical sulfuration agents. Strategically, employing easily synthesized thioformates as thiyl radical precursors allows access to various aryl and alkyl thioethers in good to excellent yields. Notably, this redox-neutral method avoids the utilization of strong bases, external ligands, forcing reaction conditions, and stoichiometric manganese, thus presenting apparent advantages, such as broad substrate scope, excellent functional group compatibility, and mild reaction conditions. Finally, the utilities of this method are also illustrated by downstream transformations and late-stage thiolation of structurally complex natural products and pharmaceuticals.

Establishing a predictive model for tumor mutation burden status based on CT radiomics and clinical features of non-small cell lung cancer patients.

Background: Tumor mutation burden (TMB) is one of the biomarkers for efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Due to the potential of radiomic signatures to identify microscopic genetic and molecular differences, thus radiomics is considered a suitable tool for judging the TMB status probably. In this paper, the radiomics method was applied to analyze the TMB status of NSCLC patients, so as to construct a prediction model for distinguishing between TMB-high and TMB-low status. Methods: A total of 189 NSCLC patients with TMB detection result were retrospectively included between 30 November 2016 and 1 January 2021, and were divided into two groups: TMB-high (≥10/Mb, 46 patients) and TMB-low (<10/Mb, 143 patients). Some clinical features related to TMB status were screened out in 14 clinical features and 2,446 radiomic features were extracted. All patients were randomly divided into a training set (n=132) and a validation set (n=57). Univariate analysis and least absolute shrinkage and selection operator (LASSO) were used for radiomics feature screening. A clinical model, radiomics model, and nomogram were constructed with the above screened features and compared. Decision curve analysis (DCA) was used to evaluate the clinical value of the established models. Results: Two clinical features (smoking history, pathological type) and 10 radiomics features were significantly correlated with the TMB status. The prediction efficiency of the intra-tumoral model was better than that of the peritumoral model (AUC: 0.819 vs. 0.816; accuracy: 0.773 vs. 0.632, specificity: 0.767 vs. 0.558). The efficacy of the prediction model based on radiomic features was significantly better than that of the clinical model (AUC: 0.822 vs. 0.683; specificity: 0.786 vs. 0.643). The nomogram, established by combining smoking history, pathologic type, and rad-score, showed the best diagnostic efficacy (AUC =0.844) and had potential clinical value in assessing the TMB status of NSCLC. Conclusions: The radiomics model based on CT images of NSCLC patients performed well in distinguishing the status of TMB-high and TMB-low, and the nomogram could provide additional information on the timing and regimen of immunotherapy.

Sex-lethal regulates back-splicing and generation of the sex-differentially expressed circular RNAs.

Conversely to canonical splicing, back-splicing connects the upstream 3' splice site (SS) with a downstream 5'SS and generates exonic circular RNAs (circRNAs) that are widely identified and have regulatory functions in eukaryotic gene expression. However, sex-specific back-splicing in Drosophila has not been investigated and its regulation remains unclear. Here, we performed multiple RNA analyses of a variety sex-specific Drosophila samples and identified over ten thousand circular RNAs, in which hundreds are sex-differentially and -specifically back-spliced. Intriguingly, we found that expression of SXL, an RNA-binding protein encoded by Sex-lethal (Sxl), the master Drosophila sex-determination gene that is only spliced into functional proteins in females, promoted back-splicing of many female-differential circRNAs in the male S2 cells, whereas expression of a SXL mutant (SXLRRM) did not promote those events. Using a monoclonal antibody, we further obtained the transcriptome-wide RNA-binding sites of SXL through PAR-CLIP. After splicing assay of mini-genes with mutations in the SXL-binding sites, we revealed that SXL-binding on flanking exons and introns of pre-mRNAs facilitates back-splicing, whereas SXL-binding on the circRNA exons inhibits back-splicing. This study provides strong evidence that SXL has a regulatory role in back-splicing to generate sex-specific and -differential circRNAs, as well as in the initiation of sex-determination cascade through canonical forward-splicing.

Effect of decay behavior of information on disease dissemination in multiplex network.

The diseases dissemination always brings serious problems in the economy and livelihood issues. It is necessary to study the law of disease dissemination from multiple dimensions. Information quality about disease prevention has a great impact on the dissemination of disease, that is because only the real information can inhibit the dissemination of disease. In fact, the dissemination of information involves the decay of the amount of real information and the information quality becomes poor gradually, which will affect the individual's attitude and behavior towards disease. In order to study the influence of the decay behavior of information on disease dissemination, in the paper, an interaction model between information and disease dissemination is established to describe the effect of the decay behavior of information on the coupled dynamics of process in multiplex network. According to the mean-field theory, the threshold condition of disease dissemination is derived. Finally, through theoretical analysis and numerical simulation, some results can be obtained. The results show that decay behavior is a factor that greatly affects the disease dissemination and can change the final size of disease dissemination. The larger the decay constant, the smaller final size of disease dissemination. In the process of information dissemination, emphasizing key information can reduce the impact of decay behavior.

The impact of the self-recognition ability and physical quality on coupled negative information-behavior-epidemic dynamics in multiplex networks.

In recent years, as the COVID-19 global pandemic evolves, many unprecedented new patterns of epidemic transmission continue to emerge. Reducing the impact of negative information diffusion, calling for individuals to adopt immunization behaviors, and decreasing the infection risk are of great importance to maintain public health and safety. In this paper, we construct a coupled negative information-behavior-epidemic dynamics model by considering the influence of the individual's self-recognition ability and physical quality in multiplex networks. We introduce the Heaviside step function to explore the effect of decision-adoption process on the transmission for each layer, and assume the heterogeneity of the self-recognition ability and physical quality obey the Gaussian distribution. Then, we use the microscopic Markov chain approach (MMCA) to describe the dynamic process and derive the epidemic threshold. Our findings suggest that increasing the clarification strength of mass media and enhancing individuals' self-recognition ability can facilitate the control of the epidemic. And, increasing physical quality can delay the epidemic outbreak and leads to suppress the scale of epidemic transmission. Moreover, the heterogeneity of the individuals in the information diffusion layer leads to a two-stage phase transition, while it leads to a continuous phase transition in the epidemic layer. Our results can provide favorable references for managers in controlling negative information, urging immunization behaviors and suppressing epidemics.

Directed Asymmetric Nickel-Catalyzed Reductive 1,2-Diarylation of Electronically Unactivated Alkenes.

Transition-metal catalyzed intermolecular 1,2-diarylation of electronically unactivated alkenes has emerged as an extensive research topic in organic synthesis. However, most examples are mainly limited to terminal alkenes. Furthermore, transition-metal catalyzed asymmetric 1,2-diarylation of unactivated alkenes still remains unsolved and is a formidable challenge. Herein, we describe a highly efficient directed nickel-catalyzed reductive 1,2-diarylation of unactivated internal alkenes with high diastereoselectivities. More importantly, our further effort towards enantioselective 1,2-diarylation of the unactivated terminal and challenging internal alkenes is achieved, furnishing various polyarylalkanes featuring benzylic stereocenters in high yields and with good to high enantioselectivities and high diastereoselectivities. Interestingly, the generation of cationic Ni-catalyst by adding alkali metal fluoride is the key to increased efficiency of this enantioselective reaction.

Advances in the diagnosis and treatment of gallbladder carcinoma / 临床肝胆病杂志

Gallbladder carcinoma is a common malignant tumor of the biliary system characterized by poor specificity of early symptoms， a high degree of malignancy， and rapid progression， and it is difficult to make an early diagnosis. Gallstones and gallbladder polyps are considered the most common risk factors for gallbladder carcinoma. Ultrasound is the preferred examination， while CT， MRI， and PET also have their own advantages. There is a lack of radical treatment methods for gallbladder carcinoma， and surgical operation remains the preferred treatment method for gallbladder carcinoma； however， due to the rapid progression of this disease， most patients have lost the opportunity for surgery at the time of diagnosis. A combination of various treatment modalities， such as radiochemotherapy， targeted therapy， and immunotherapy， has improved the prognosis of patients to a certain extent， but with an unsatisfactory long-term therapeutic effect. Therefore， it is of particular importance to give priority to prevention rather than treatment and emphasize early identification and treatment.

Endobronchial valve therapy for patients with advanced emphysema. A report from a tertiary care center in China.

OBJECTIVES: To assess the efficiency and safety of endobronchial valve (EBV) treatment in Chinese patients. METHODS: A retrospective analysis was performed in patients with chronic obstructive pulmonary disease who underwent EBV implantation in our hospital between October 2010 and January 2017. All patients were confirmed with no collateral ventilation (CV-) or with low airflow (LF) in the treated lobe. Pulmonary function parameters, the 6-minute walk distance (6MWD), the modified Medical Research Council (mMRC), as well as adverse events in the follow-up period were recorded. RESULTS: Thirty-eight advanced emphysema patients received EBV implantation. Significant improvements were found in forced expiratory volume in 1 second (FEV1)(FEV1: +0.12 L), 6MWD (+64.9 m), and mMRC (-0.5 points). A total of 55.3% and 65.8% of subjects met the score for the minimal clinically important difference in FEV1 and 6MWD, respectively. FEV1 improved more significantly in the CV- group than in the LF group. Pneumothorax or death did not occur during the follow-up period. CONCLUSION: Endobronchial valve treatment in patients with advanced emphysema and CV- provides clinically meaningful benefits with a low incidence of pneumothorax. The efficiency and safety of EBV therapy are acceptable in China.

Nickel-Catalyzed Enantioselective Coupling of Acid Chlorides with α-Bromobenzoates: An Asymmetric Acyloin Synthesis.

The reaction of common acyl-metal species (acyl anion) with aldehydes to furnish acyloins has received much less attention and specifically was restricted to using preformed stoichiometric acyl-metal reagents. Moreover, the (catalytic) enantioselective variants remain unexplored, and the asymmetric synthesis of chiral acyloins has met significant challenges in organic synthesis. Here, we uncover the highly enantioselective coupling of acid chlorides with α-bromobenzoates by nickel catalysis for producing enantioenriched protected α-hydroxy ketones (acyloins, >60 examples) with high enantioselectivities (up to 99% ee). The successful execution of this enantioselective coupling protocol enables the formation of a key ketyl radical from α-bromoalkyl benzoate in situ generated from corresponding aldehyde and acyl bromide, which finally is captured by chiral acyl-Ni species catalytically in situ formed from acyl chlorides, thus avoiding the use of preformed acyl-metal reagents. The synthetic utility of this chemistry is demonstrated in the downstream synthetic elaboration toward a diverse set of synthetically valuable chiral building blocks and biologically active compounds.

Development and application of a novel model to predict the risk of non-alcoholic fatty liver disease among lean pre-diabetics with normal blood lipid levels.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been associated with type 2 diabetes, but its relationship with pre-diabetes is still unknown. This study aims to determine whether pre-diabetes is associated with NAFLD, followed by establishing a NAFLD predictive nomogram for lean Chinese pre-diabetics with normal blood lipids. METHODS: Datasets from 3 previous studies, 1 (2774 pre-diabetics with normal blood lipids for training, 925 for validation), 2 (546 for longitudinal internal validation, post-5-year follow-up), and 3 (501 from another institution for external validation), were used. Kaplan-Meier determined cumulative NAFLD hazard, and least absolute shrinkage and selection operator regression analysis uncovered its risk factors. Multivariate logistic regression analysis constructed the nomogram, followed by validation with receiver operating characteristic curve, calibration plot, and decision curve analyses. RESULTS: NAFLD incidence increased with diabetes progression, and pre-diabetics had higher cumulative risk versus non-diabetics, even for lean individuals with normal blood lipids. Six risk factors were identified: body mass index, total cholesterol, alanine aminotransferase:aspartate aminotransferase, triglyceride:high density lipoprotein cholesterol, fasting blood glucose and γ-glutamyl-transferase. The nomogram yielded areas under the curve of 0.808, 0.785, 0.796 and 0.832, for respectively, training, validation, longitudinal internal validation, and external validation, which, along with calibration curve values of p = 0.794, 0.875, 0.854 and 0.810 for those 4 datasets and decision curve analyses, validated its clinical utility. CONCLUSIONS: Lean pre-diabetic Chinese with normal blood lipids have higher NAFLD risk versus non-diabetics. The nomogram is able to predict NAFLD among such individuals, with high discrimination, enabling its use for early detection and intervention.

The combination of serum oligosaccharide chain (G-test), alpha-fetoprotein, and aspartate aminotransferase to alanine aminotransferase ratio provides the optimal diagnostic value for early detection of hepatocellular carcinoma.

BACKGROUND: The purpose of this study was to compare the diagnostic value of serum oligosaccharide chain (G-test), alpha-fetoprotein (AFP) and aspartic aminotransferase to alanine aminotransferase ratios (AAR), both alone and in combination, for predicting hepatocellular carcinoma (HCC) onset. METHODS: Between Januarys 2020-2022, 152 subjects admitted to the First Affiliated Hospital of Nanchang University was enrolled in this study, of which 77 had HCC, 18 chronic hepatitis (CH), 37 liver cirrhosis (LC) and 20 were healthy. Data for patient characteristics were collected, and differences between groups were analyzed by either Mann-Whitney U or χ2 tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of AFP, G-test, and AAR for HCC. RESULTS: G-test, AFP, and AAR were all found to have close correlations with HCC among the different patient groups, with G-test being the most predictive for HCC among healthy and CL patients, as represented by respective areas under the curve (AUC) of 0.953 and 0.792 (P < 0.001). By contrast, AAR had the greatest diagnostic ability for HCC among CH patients (AUC = 0.850; P < 0.001). However, the combination of all 3 biomarkers obtained the most optimal results for predicting HCC onset, in terms of predictive capability for all 3 non-HCC patient groups, yielding AUCs of 0.958, 0.898, and 0.808 (P < 0.001) for, respectively, healthy, CH, and LC patients. Additionally, AFP had higher specificity, but lower sensitivity, with increased threshold values, as the recommended threshold of AFP ≥ 400 ng/mL yielded a missed diagnosis rate of 72.7%. For AFP-negative HCC (AFP-NHCC) patients, G-test alone had the greatest diagnostic capability (AUC = 0.855; P < 0.001), sensitivity (83.8%), and specificity (87.5%). CONCLUSION: G-test has the greatest diagnostic capability for HCC and AFP-NHCC, with high sensitivity and specificity, among healthy and LC patients. However, AAR had the highest diagnostic capability and sensitivity for HCC in CH. Overall, though, the combination of G-test, AFP and AAR provided the most optimal outcomes for predicting HCC onset, no matter the patient pre-conditions.