MHBase: A comprehensive database of short microhaplotypes for advancing forensic genetic analysis.

Microhaplotypes (MHs) were first recommended by Prof. Kidd for use in forensics because they can improve human identification, kinship analysis, mixture deconvolution, and ancestry prediction. Since their introduction, extensive research has demonstrated the advantages of MHs in forensic applications and provided useful data for different populations. Currently, two databases, ALFRED (ALlele FREquency Database) and MicroHapDB (MicroHaplotype DataBase), house the published MH information and population data. We previously constructed a single nucleotide polymorphism SNP-SNP MH database (D-SNPsDB) of MHs within 50 bp on the whole human genome for 26 populations integrating basic data such as physical genome positions, mapping of variant identifiers (rsIDs), allele frequencies, and basic variant information. Building upon the previous research, we further selected MHs containing at least two variants (SNPs and/or insertions/deletions [InDels]) within a short DNA fragment (≤ 50 bp) in 26 populations based on the 1000 Genomes Project dataset (Phase 3) to construct a more comprehensive database. Subsequently, we established a user-friendly website that allows users to search the MH database (MHBase) based on their research objectives and study population to find suitable loci and provides other functions such as querying reported loci, performing online calculations using the PHASE software, and calculating ancestral-related parameters. The loci in the database are classified as SNP-based MHs, which include only SNPs, and InDel-including MHs, which contain at least one InDel. Here, we provide a detailed overview of the MHBase and an analysis of shared loci at the global and continental levels, ancestral markers, the genetic distance within loci, and mapping with the genome annotation file. The website is an accessible and useful tool for researchers engaged in marker discovery, population studies, assay development, and panel design.

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches.

Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.

Characterization of posterior circulation blood perfusion in patients with different degrees of basilar artery tortuosity.

OBJECTIVE: The morphology of basilar artery (BA) may affect posterior circulation blood perfusion. We aimed to investigate whether different degrees of BA tortuosity could lead to the alterations of posterior circulation perfusion. METHODS: We collected 138 subjects with different BA tortuosity scores, including 32 cases of score 0, 45 cases of score 1, 43 cases of score 2, and 18 cases of score 3. A higher score represented a higher degree of BA tortuosity. Ordered logistic regression analysis was performed to investigate the risk factors for BA tortuosity. We quantitatively measured the cerebral blood flow (CBF) in eight posterior circulation brain regions using arterial spin labeling. SPSS 25.0 was used for statistical analysis. The correlation between the CBF and BA tortuosity was corrected by the Bonferroni method. The significance level was set at 0.006 (0.05/8). RESULTS: Hypertension (HR: 2.39; 95%CI: 1.23-4.71; P = 0.01) and vertebral artery dominance (HR: 2.38; 95%CI: 1.10-4.67; P = 0.03) were risk factors for BA tortuosity. CBF in occipital gray matter (R = -0.383, P < 0.001), occipital white matter (R = -0.377, P < 0.001), temporal gray matter (R = -0.292, P = 0.001), temporal white matter (R = -0.297, P < 0.001), and cerebellum (R = -0.328, P < 0.001) were negatively correlated with BA tortuosity degree. No significant correlation was found between the BA tortuosity degree and CBF in hippocampus (R = -0.208, P = 0.014), thalamus (R = -0.001, P = 0.988) and brainstem (R = -0.204, P = 0.016). CONCLUSIONS: BA tortuosity could affect posterior circulation blood perfusion. CBF was negatively correlated with BA tortuosity degree. The morphology of BA may serve as a biomarker for posterior circulation and the severity of posterior circulation ischemia.

Childhood maltreatment, parenting style and anxiety in Chinese youths: A case-control study.

BACKGROUND: Although evidence in supporting the associations between childhood maltreatment (CM), parenting style and anxiety in children and adolescents exists, few high-quality analytical epidemiological studies which focusing on clinically diagnosed anxiety disorders (AD) had been published. OBJECTIVE: The aim of this study was to further corroborate the associations between CM, parenting style, and AD in a large representative sample of Chinese children and adolescents. PARTICIPANTS AND SETTING: Study subjects were derived from the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a population-based cross-sectional program. METHODS: Individually matched case-control study design was adopted. Univariate and multivariate conditional binary logistic regression models were used to estimate the associations between CM, parenting style and AD. Dose-response trends were estimated using the Cochran-Armitage Chi-square test. A series of stratified analyses were conducted to explore effect modification on exposure-outcome association by some important features. RESULTS: Totally we screened out 202 cases and 404 matched controls, with an age mean of 14.43 years. Conditional logistic regression models revealed that EA and a higher level of parental over-protection were significantly associated with increased risk of AD, with adjusted ORs of 3.39 (95 % CI: 2.07-5.56) and 1.93 (95 % CI: 1.28-2.90). Stratified analysis identified noticeable effect modification by sex, age, and whether the only child in the family. CONCLUSIONS: Major findings of this study suggested that children and adolescents who had experienced EA or raised up by over-protective parents are at increased risk of AD. Targeted intervention measures should be developed and implemented for these high-risk youths.

Developmental validation of an mRNA kit: A 5-dye multiplex assay designed for body-fluid identification.

Identifying the sources of biosamples found at crime scenes is crucial for forensic investigations. Among the markers used for body fluid identification (BFI), mRNA has emerged as a well-studied marker because of its high specificity and remarkable stability. Despite this potential, commercially available mRNA kits specifically designed for BFI are lacking. Therefore, we developed an mRNA kit that includes 21 specific mRNA markers of body fluids, along with three housekeeping genes for BFI, to identify four forensic-relevant fluids (blood, semen, saliva, and vaginal fluids). In this study, we tested 451 single-body-fluid samples, validated the universality of the mRNA kit, and obtained a gene expression profile. We performed the validation studies in triplicates and determined the sensitivity, specificity, stability, precision, and repeatability of the mRNA kit. The sensitivity of the kit was found to be 0.1 ng. Our validation process involved the examination of 59 RNA mixtures, 60 body fluids mixtures, and 20 casework samples, which further established the reliability of the kit. Furthermore, we constructed five classifiers that can handle single-body fluids and mixtures using this kit. The classifiers output possibility values and identify the specific body fluids of interest. Our results showed the reliability and suitability of the BFI kit, and the Random Forest classifier performed the best, with 94% precision. In conclusion, we developed an mRNA kit for BFI which can be a promising tool for forensic practice.

Analysis of cantharidin-induced kidney injury and the protective mechanism of resveratrol in mice determined by liquid chromatography/mass spectrometry-based metabonomics.

Cantharidin (CTD) is the main active component in the traditional Chinese medicine Mylabris and an effective anti-tumor agent. However, it is relatively toxic and exhibits nephrotoxicity, which limits its clinical use. However, its toxic mechanism is not clear. The toxic effects of CTD exposure on the kidney and the protective effect of resveratrol (RES) were studied in a mouse model, by determination of serum biochemical and renal antioxidant indicators, histopathological and ultrastructural observation, and metabonomics. After CTD exposure, serum uric acid, creatinine, and tissue oxidative stress indicators increased, and the renal glomerular and tubular epithelial cells showed clear pathological damage. Ultrastructure observation revealed marked mitochondrial swelling, endoplasmic reticulum dilation, and the presence of autophagy lysosomes in glomerular epithelial cells. RES ameliorated the renal injury induced by CTD. Metabonomics analysis indicated that CTD can induce apoptosis and oxidative damage in kidney cells, mainly by disrupting sphingolipid and glutathione metabolism, increasing sphingosine and sphingomyelin levels, and decreasing glutathione levels. RES counteracts these effects by regulating renal cell proliferation, the inflammatory response, oxidative stress, and apoptosis, by improving the levels of phosphatidylcholine (PC), LysoPC, and lysophosphatidyl glycerol in the glycerophospholipid metabolism pathway, thereby reducing CTD-induced nephrotoxicity. The mechanisms of CTD-induced renal injury and the protective effect of RES were revealed by metabonomics, providing a basis for evaluating clinical treatment regimens to reduce CTD-induced nephrotoxicity.

Development of a coding SNP panel for tracking the origin of whole-exome sequencing samples.

Whole-exome sequencing (WES) is widely used to diagnose complex genetic diseases and rare conditions. The implementation of a robust and effective quality control system for sample identification and tracking throughout the WES process is essential. We established a multiplex panel that included 22 coding single-nucleotide polymorphism (cSNP) loci. The personal identification and paternity identification abilities of the panel were evaluated, and a preliminary validation of the practical feasibility of the panel was conducted in a clinical WES case. These results indicate that the cSNP panel could be a useful tool for sample tracking in WES.

Social poverty indicators with school bullying victimization: evidence from the global school-based student health survey (GSHS).

BACKGROUND: School bullying is prevalent in children and adolescents. Bullying victims are seen higher risk of negative psychological outcomes. Previously published studies suggested that social indicators may pose significant influence on bullying victimization. However, the association between social poverty and bullying victimization has not been exclusively discussed. METHODS: In this cross-sectional study, we analyzed the association between 6 commonly used social poverty indicators (Poverty Headcount Ratio, PHR; Poverty Gap, PG; Squared Poverty Gap, SPG; monthly household per capita income, PCI; Watts' Poverty Index, WPI; the Gini Index, Gini) and the prevalence of school bullying at country level by using the Global school-based Student Health Survey (GSHS) database. RESULTS: Altogether 16 countries were included into the final analysis, with school bullying victimization prevalence ranged from 12.9 to 47.5%. Bubble plots revealed statistically significant associations between the three indicators measuring absolute poverty level (PHR, PCI, WPI) and bullying victimization. Subsequently performed principal component regression indicated that, for all types of bullying victimization, the increase of absolute poverty level was related to elevated prevalence rates, and the association was particularly strong for verbal bullying victimization. CONCLUSIONS: Our study results may suggest that absolute social poverty is an important parameter for constructing and implementing school bullying victimization intervention strategies and measures.

Optimizing Analytical Thresholds for Low-Template DNA Analysis: Insights from Multi-Laboratory Negative Controls.

When analyzing challenging samples, such as low-template DNA, analysts aim to maximize information while minimizing noise, often by adjusting the analytical threshold (AT) for optimal results. A potential approach involves calculating the AT based on the baseline signal distribution in electrophoresis results. This study investigates the impact of reagent kits, testing quarters, environmental conditions, and amplification cycles on baseline signals using historical records and experimental data on low-template DNA. Variations in these aspects contribute to differences in baseline signal patterns. Analysts should remain vigilant regarding routine instrument maintenance and reagent replacement, as these may affect baseline signals. Prompt analysis of baseline status and tailored adjustments to ATs under specific laboratory conditions are advised. A comparative analysis of published methods for calculating the optimal AT from a negative signal distribution highlighted the efficiency of utilizing baseline signals to enhance forensic genetic analysis, with the exception of extremely low-template samples and high-amplification cycles. Moreover, a user-friendly program for real-time analysis was developed, enabling prompt adjustments to ATs based on negative control profiles. In conclusion, this study provides insights into baseline signals, aiming to enhance genetic analysis accuracy across diverse laboratories. Practical recommendations are offered for optimizing ATs in forensic DNA analysis.

Etanercept Combined with Glucocorticoid and Gamma Globulin for Treating Children with Toxic Epidermal Necrolysis: A Case Report.

Toxic epidermal necrolysis (TEN) is a type of drug eruption in dermatology emergencies that is rare in clinical practice but has a high mortality rate. The main causes are drug and viral infections. Unfortunately, no expert consensus on treating this disease exists, and a standard therapy is absent. Up to now, glucocorticoids combined with gamma globulin are commonly used in clinical practice, but their efficacy is highly controversial. This study reports on a 7-year-old girl with TEN who did not respond to traditional therapy, such as methylprednisolone combined with gamma globulin, but was finally cured with an additional low-dose etanercept. The results showed that etanercept therapy in paediatric TEN is safe, reliable and worth recommending.

Improving DNA mixtures analysis using compound markers composed of InDels and SNPs screened from the whole genome with next-generation sequencing.

Next-generation sequencing (NGS) allows for better identification of insertion and deletion polymorphisms (InDels) and their combination with adjacent single nucleotide polymorphisms (SNPs) to form compound markers. These markers can improve the polymorphism of microhaplotypes (MHs) within the same length range, and thus, boost the efficiency of DNA mixture analysis. In this study, we screened InDels and SNPs across the whole genome and selected highly polymorphic markers composed of InDels and/or SNPs within 300 bp. Further, we successfully developed and evaluated an NGS-based panel comprising 55 loci, of which 24 were composed of both SNPs and InDels. Analysis of 124 unrelated Southern Han Chinese revealed an average effective number of alleles (Ae ) of 7.52 for this panel. The cumulative power of discrimination and cumulative probability of exclusion values of the 55 loci were 1-2.37 × 10-73 and 1-1.19 × 10-28 , respectively. Additionally, this panel exhibited high allele detection rates of over 97% in each of the 21 artificial mixtures involving from two to six contributors at different mixing ratios. We used EuroForMix to calculate the likelihood ratio (LR) and evaluate the evidence strength provided by this panel, and it could assess evidence strength with LR, distinguishing real and noncontributors. In conclusion, our panel holds great potential for detecting and analyzing DNA mixtures in forensic applications, with the capability to enhance routine mixture analysis.

Cantharidin-induced toxic injury, oxidative stress, and autophagy attenuated by Astragalus polysaccharides in mouse testis.

Cantharidin (CTD) is a chemical constituent derived from Mylabris and has good antitumor effects, but its clinical use is restricted by its inherent toxicity. However, few researches have reported its reproductive toxicity and mechanisms. This study aims to assess CTD's toxicity on mouse testes and the protective effect of Astragalus polysaccharides (APS). Briefly, biochemical analysis, histopathology, transmission electron microscopy, immunohistochemistry, and Western blotting were used to evaluate the oxidative damage of mouse testicular tissue after exposure to CTD and treatment by APS. Our research suggests a dramatic decrease in testicular index and serum testosterone levels after CTD exposure. The testis showed obvious oxidative damage accompanied by an increase in mitochondrial autophagy, the Nfr2-Keap1 pathway was inhibited, and the blood-testis barrier was destroyed. Notably, these changes were significantly improved after APS treatment. The internal mechanisms of APS ameliorate CTD-induced testicular oxidative damage in mice may be closely connected to regulatory the Nrf2-Keap1 signaling pathway, restraining autophagy, and repairing the blood-testis barrier, providing theoretical support for further study on the reproductive toxicity mechanism of CTD and clinical treatments to ameliorate it.

GLP1R rs3765467 Polymorphism Is Associated with the Risk of Early Onset Type 2 Diabetes.

Objective: To investigate the relationship between glucagon-like peptide-1 receptor gene polymorphisms and susceptibility to early onset type 2 diabetes. Methods: Samples from 316 type 2 diabetes patients with early onset type 2 diabetes (n = 137) and late-onset type 2 diabetes (n = 179) and 145 nondiabetic individuals were analyzed. Multiplex PCR combined with resequencing Hi-Reseq technology was used to detect single nucleotide polymorphisms of the glucagon-like peptide-1 receptor gene, and the allele frequency, genotype distribution, and clinical parameters were analyzed between each diabetes subgroup and the control group. Results: Sixteen single nucleotide polymorphisms were identified in the exonic region of the glucagon-like peptide-1 receptor gene according to the minor allele frequency (MAF > 0.05) in the participants. Among these, the glucagon-like peptide-1 receptor rs3765467 (G⟶A) mutation was statistically associated with early onset type 2 diabetes. Compared with that of the GG carriers, carriers of genotype AA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. In the dominant model, the frequencies of the rs3765467 AA + GA genotype were significantly decreased in the early onset type 2 diabetes group, and carriers of genotype AA + GA at rs3765467 had a decreased risk of early onset type 2 diabetes after adjusting for sex and body mass index. Moreover, fasting C peptide levels were significantly higher in GA + AA genotype carriers than those in GG genotype carriers. Conclusion: The glucagon-like peptide 1 receptor rs3765467 polymorphism was significantly associated with age at type 2 diabetes diagnosis and thus may be used as a marker to screen and detect individuals at risk of developing early onset type 2 diabetes.

Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis.

BACKGROUND: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. METHODS: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). RESULTS: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. CONCLUSION: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.

Treatment Rates for Mental Disorders Among Children and Adolescents: A Systematic Review and Meta-Analysis.

Importance: Mental disorders among children and adolescents are global health concerns. Published studies have provided discordant results regarding treatment rates for mental disorders among youths. Objective: To estimate combined treatment rates for several common psychiatric disorders among children and adolescents. Data Sources: PubMed, Web of Science, PsycINFO, Scopus, and Embase were searched from database inception until September 23, 2022, and supplemented with hand-searching of reference lists. Study Selection: Included studies were those that used validated methods to report treatment rates for any mental disorder, depressive disorders, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and behavior disorders among children and adolescents. Data Extraction and Synthesis: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Two reviewers independently assessed study eligibility, extracted data, and scored quality. Studies with a Joanna Briggs Institute score of 5 or more were included in the meta-analysis. Treatment rates were pooled using random-effects models. Subgroup analyses were performed to investigate the association with treatment rates of factors, such as year of data collection, World Health Organization region, age, income level, timeframe of diagnosis, informant source, service type, sample origin, and internalizing or externalizing disorder. Main Outcomes and Measures: Treatment rates for mental disorders among children and adolescents were the main outcomes, measured as percentage estimates. Results: Forty studies were included in the analysis, comprising 310 584 children and adolescents, with boys accounting for 39% of participants (sex was not reported in 10 studies). The pooled treatment rate was 38% (95% CI, 30%-45%) for any mental disorder, 36% (95% CI, 29%-43%) for depressive disorders, 31% (95% CI, 21%-42%) for anxiety disorders, 58% (95% CI, 42%-73%) for ADHD, and 49% (95% CI, 35%-64%) for behavior disorders. Age, income level, and region were significantly associated with the combined treatment rates of mental disorders in children and adolescents. The treatment rate for depressive disorders was higher among adolescents than children (36% [95% CI, 25%-46%] vs 11% [95% CI, 0%-25%]), whereas the treatment rate for anxiety disorders was higher among children than adolescents (64% [95% CI, 52%-75%] vs 20% [95% CI, 9%-30%]). The treatment rate for any mental disorder in lower-middle income countries was 6% (95% CI, 2%-14%), in upper-middle income countries was 24% (95% CI, 2%-47%), and in high-income countries was 43% (95% CI, 35%-52%). For depressive disorders, treatment rates were higher in the Americas (40% [95% CI, 30%-51%]) than in Europe (28% [95% CI, 13%-43%]) and the Western Pacific region (6% [95% CI, 1%-16%]). Conclusions and Relevance: This study suggests that, in general, the treatment rates for mental disorders among children and adolescents were low, especially for depression and anxiety. Targeted intervention policies and effective measures should be designed and implemented to improve treatment rates of psychiatric disorders among youths.

Selenium Modification of Natural Products and Its Research Progress.

The selenization of natural products refers to the chemical modification method of artificially introducing selenium atoms into natural products to interact with the functional groups in the target molecule to form selenides. Nowadays, even though scientists in fields involving organic selenium compounds have achieved numerous results due to their continuous investment, few comprehensive and systematic summaries relating to their research results can be found. The present paper summarizes the selenization modification methods of several kinds of important natural products, such as polysaccharides, proteins/polypeptides, polyphenols, lipids, and cyclic compounds, as well as the basic principles or mechanisms of the selenizing methods. On this basis, this paper explored the future development trend of the research field relating to selenized natural products, and it is hoped to provide some suggestions for directional selenization modification and the application of natural active ingredients.

Assessment of early diabetic retinopathy severity using ultra-widefield Clarus versus conventional five-field and ultra-widefield Optos fundus imaging.

To compare early diabetic retinopathy (DR) severity level and the abilities in detecting early DR lesions among conventional five-field, ultrawide-field (UWF) Optos, and UWF Clarus fundus imaging methods. This was a single-center, prospective, clinic-based, and comparative study. In total, 157 consecutive patients with diabetes mellitus were enrolled in this study. All patients underwent comprehensive ophthalmological examinations. Following mydriasis, each eye was examined with conventional five-field, UWF Optos, and UWF Clarus fundus imaging methods. The initial UWF images were overlaid with a template mask that obscured the retina, which created a five-field view from UWF images (covered UWF images). The covered UWF images were then graded, after which the template mask was removed, and the original UWF images were also evaluated. All images were graded using the International Clinical DR severity scale. DR grades were compared and analyzed by weighted kappa statistics among the three fundus imaging methods. In total, 157 consecutive patients with diabetes (302 eyes) were enrolled in this study. Weighted kappa statistics for agreement were 0.471 (five-field vs. covered Optos), 0.809 (five-field vs. covered Clarus), 0.396 (covered Optos vs. covered Clarus), 0.463 (five-field vs. Optos), 0.521 (five-field vs. Clarus 133°), 0.500 (five-field vs. Clarus 200°), 0.323 (Optos vs. Clarus 133°), and 0.349 (Optos vs. Clarus 200°). The area under curve of covered Clarus images was higher than that of conventional five-field images at three different thresholds. Compared with conventional five-field and Optos fundus imaging methods, Clarus fundus imaging methods exhibited excellent performance in assessing early DR severity. Thus, Clarus fundus imaging methods were superior for early detection of DR.

Fibrinogen-to-albumin ratio predicts overall survival of hepatocellular carcinoma.

BACKGROUND: Fibrinogen-to-albumin ratio (FAR) has been found to be of prognostic significance for several types of malignant tumors. However, less is known about the association between FAR and survival outcomes in hepatocellular carcinoma (HCC) patients. AIM: To explore the association between FAR and prognosis and survival in patients with HCC. METHODS: A total of 366 histologically confirmed HCC patients diagnosed between 2013 and 2018 in a provincial cancer hospital in southwestern China were retrospectively selected. Relevant data were extracted from the hospital information system. The optimal cutoff for baseline serum FAR measured upon disease diagnosis was established using the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox proportional hazards models were used to determine the crude and adjusted associations between FAR and the overall survival (OS) of the HCC patients while controlling for various covariates. The restricted cubic spline (RCS) was applied to estimate the dose-response trend in the FAR-OS association. RESULTS: The optimal cutoff value for baseline FAR determined by the ROC was 0.081. Multivariate Cox proportional hazards model revealed that a lower baseline serum FAR level was associated with an adjusted hazard ratio of 2.43 (95% confidence interval: 1.87-3.15) in the OS of HCC patients, with identifiable dose-response trend in the RCS. Subgroup analysis showed that this FAR-OS association was more prominent in HCC patients with a lower baseline serum aspartate aminotransferase or carbohydrate antigen 125 level. CONCLUSION: Serum FAR is a prominent prognostic indicator for HCC. Intervention measures aimed at reducing FAR might result in survival benefit for HCC patients.