Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-𝜠B pathway.

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 µM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

Dibenzocyclooctadiene lignans from Kadsura coccinea alleviate APAP-induced hepatotoxicity via oxidative stress inhibition and activating the Nrf2 pathway in vitro.

Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1-5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1-68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 µM. The structure-activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway.

New Cadinane Sesquiterpenes from the Stems of Kadsura heteroclita.

As part of our continual efforts to exploit 'Tujia Ethnomedicine' for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6α,9α,15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (-)-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4-7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 µM on isolated human polymorphonuclear cells or neutrophils.

An ultrasensitive and simple method for alkaline phosphatase assay and targeted natural compound screening in vitro.

As an essential phosphate group hydrolase, alkaline phosphatase (ALP), whose level in serum is correlated with bone disease, liver dysfunction, and cancer, could be used as a biomarker for clinical diagnosis and biomedical studies. Hence, developing a convenient and sensitive method for ALP assay has importance in disease diagnosis, drug treatment, and prognosis assessment. In this work, using a hairpin DNA strand as the substrate, we developed an ultrasensitive and simple fluorescence method for quantitative ALP assay based on the binding difference of reduced graphene oxide (rGO) with different DNA strands coupled with λ exonuclease (λ exo) cleavage. Under the optimal conditions, the limit of detection (LOD) of ALP is estimated to be 0.01 U/L with the linear region from 0.5 U/L to 70 U/L. Furthermore, the proposed assay was used to detect ALP in complicated cell-free extracts and evaluate the inhibitory effects of two well-known inhibitors of ALP activity. Finally, the method was used to investigate the effect of natural compounds on ALP activity and five compounds with different inhibitory capability were screened. In summary, we propose that the new method for ALP assay can be applied for therapeutic drug monitoring (TDM) and high-throughput compound screening in combination with multiwell plate technology.

Lignans from the bark of Zanthoxylum simulans.

Investigation on the EtOAc extract of the bark of Zanthoxylum simulans led to the isolation of four new lignans including zanthoxylumin A (1), zanthoxylumin B (2), ( - )-magnolin (3), and ( - )-pinoresinol-di-3,3-dimethylallyl ether (4). Their structures were established by comprehensive analysis of the spectral data, especially 1D and 2D NMR spectra.

Distinct Changes in Metabolic Profile and Sensory Quality with Different Varieties of Chrysanthemum (Juhua) Tea Measured by LC-MS-Based Untargeted Metabolomics and Electronic Tongue.

Chrysanthemum tea, a typical health tea with the same origin as medicine and food, is famous for its unique health benefits and flavor. The taste and sensory quality of chrysanthemum (Juhua) tea are mainly determined by secondary metabolites. Therefore, the present research adopted untargeted metabolomics combined with an electronic tongue system to analyze the correlation between the metabolite profiles and taste characteristics of different varieties of chrysanthemum tea. The results of sensory evaluation showed that there were significant differences in the sensory qualities of five different varieties of chrysanthemum tea, especially bitterness and astringency. The results of principal component analysis (PCA) indicated that there were significant metabolic differences among the five chrysanthemum teas. A total of 1775 metabolites were identified by using untargeted metabolomics based on UPLC-Q-TOF/MS analysis. According to the variable importance in projection (VIP) values of the orthogonal projections to latent structures discriminant analysis (OPLS-DA), 143 VIP metabolites were found to be responsible for metabolic changes between Huangju and Jinsi Huangju tea; among them, 13 metabolites were identified as the key metabolites of the differences in sensory quality between them. Kaempferol, luteolin, genistein, and some quinic acid derivatives were correlated with the "astringency" attributes. In contrast, l-(-)-3 phenyllactic acid and L-malic acid were found to be responsible for the "bitterness" and "umami" attributes in chrysanthemum tea. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the flavonoid and flavonol biosynthesis pathways had important effects on the sensory quality of chrysanthemum tea. These findings provide the theoretical basis for understanding the characteristic metabolites that contribute to the distinctive sensory qualities of chrysanthemum tea.

An Efficient Workflow for Quality Control Marker Screening and Metabolite Discovery in Dietary Herbs by LC-Orbitrap-MS/MS and Chemometric Methods: A Case Study of Chrysanthemum Flowers.

LC-MS is widely utilized in identifying and tracing plant-derived food varieties but quality control markers screening and accurate identification remain challenging. The adulteration and confusion of Chrysanthemum flowers highlight the need for robust quality control markers. This study established an efficient workflow by integrating UHPLC-Orbitrap-MS/MS with Compound Discoverer and chemometrics. This workflow enabled the systematic screening of 21 markers from 10,540 molecular features, which effectively discriminated Chrysanthemum flowers of different species and cultivars. The workflow incorporated targeted and untargeted methods by employing diagnostic product ions, fragmentation patterns, mzCloud, mzVault, and in-house databases to identify 206 compounds in the flowers, including 17 screened markers. This approach improved identification accuracy by reducing false positives, eliminating in-source fragmentation interference, and incorporating partial verification utilizing our established compound bank. Practically, this workflow can be instrumental in quality control, geolocation determination, and varietal tracing of Chrysanthemum flowers, offering prospective use in other plant-derived foods.

Flavonoidal alkaloids: Emerging targets for drug discovery from Nature's bounty.

This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field.

Nanomedicines targeting activated immune cells and effector cells for rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and inflammatory cellular infiltration. Functional cells in the RA microenvironment (RAM) are composed of activated immune cells and effector cells. Activated immune cells, including macrophages, neutrophils, and T cells, can induce RA. Effector cells, including synoviocytes, osteoclasts, and chondrocytes, receiving inflammatory stimuli, exacerbate RA. These functional cells, often associated with the upregulation of surface-specific receptor proteins and significant homing effects, can secrete pro-inflammatory factors and interfere with each other, thereby jointly promoting the progression of RA. Recently, some nanomedicines have alleviated RA by targeting and modulating functional cells with ligand modifications, while other nanoparticles whose surfaces are camouflaged by membranes or extracellular vesicles (EVs) of these functional cells target and attack the lesion site for RA treatment. When ligand-modified nanomaterials target specific functional cells to treat RA, the functional cells are subjected to attack, much like the intended targets. When functional cell membranes or EVs are modified onto nanomaterials to deliver drugs for RA treatment, functional cells become the attackers, similar to arrows. This study summarized how diversified functional cells serve as targets or arrows by engineered nanoparticles to treat RA. Moreover, the key challenges in preparing nanomaterials and their stability, long-term efficacy, safety, and future clinical patient compliance have been discussed here.

Stochastic bipedal dual-DNA walkers for fast and sensitive detection of apurinic/apyrimidinic endonuclease1 and inhibitor screening.

DNA walkers have emerged as a powerful tool in various biosensors, enabling the detection of low-abundance analytes with their precise programmability and efficient signal amplification capacity. However, many existing approaches are hampered by limited reaction kinetics. Herein, we designed a stochastic bipedal dual-DNA walkers (SBDW) that can traverse at high speed on AuNP-based three-dimensional (3D) tracks powered by Exo III. The SBDW exhibited superior reaction kinetics and are up to least 2.25 times faster than traditional DNA walkers, reaching a plateau within 40 min. This advancement allows for rapid and highly sensitive fluorescence detection of a significant base excision repair enzyme of APE1 with a detection limit of 0.001 U/mL. In comparison to traditional DNA walkers, this platform enables highly sensitive and specific APE1 assays in cell lysate and facilitates rapid and accurate screening of APE1 inhibitors. Given its rapid, sensitive, specific, and reliable analysis features, the strategy shows great promise in drug discovery and clinical diagnosis.

Pushing Forward the DNA Walkers in Connection with Tumor-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018-2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future.

[Study on chemical constituents of Zanthoxyli cortex's ethyl acetate extract].

OBJECTIVE: To study the chemical constituents of Zanthoxyli Cortex. METHODS: The chemical constituents were isolated and purified by silica gel and HP-20, MCI gel, Sephadex LH -20 column chromatography, RP-18 and PTLC. Their structures were elucidated by the analysis of spectral data and chemical properties. RESULTS: Ten compounds were isolated from EtOAc extract and their structures were identified as: asarinin (I), fargesin (II), eudesmin (III), (1R, 2R, 5R, 6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]-octane(IV), dimethoxysamin(V), rel-(1R,5R,6S)-6-(3,4-dimethoxyphen-yl)-3,7-dioxabicyclo-[3.3.0]-octan-2-one(VI), Magnone A(VII), beta-sitoste-rol( VIII), beta-armyrin(IX), beta-amyrone(X). CONCLUSION: These compounds isolated from Zanthoxyli Cortex's Ethyl acetate extract are all known compounds. Fargesin(II) and beta-amyrone(X) are isolated from Zanthoxyli Cortex for the first time.

Three new constituents from the Tujia ethnomedicine Swertia punicea Hemsl.

Three new constituents: 1,5R-dihydroxy-3,8S-dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3S,4R,16S,17R)-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3-O-ß-D-glucopyranoside (2), and new natural product (S)-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea. Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7, 9 and 14 showed antioxidant activities with IC50 values of 68.9, 50.8 and 48.2 µM, respectively.

A multi-center retrospective study on the efficacy and safety of regorafenib vs. regorafenib combined with PD-1 inhibitors as a second-line therapy in patients with advanced hepatocellular carcinoma.

Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the combination therapy of regorafenib and programmed death-1 (PD-1) inhibitors with regorafenib monotherapy as a second-line treatment for patients with advanced HCC. Methods: Our multicenter retrospective study evaluated consecutive patients with advanced HCC who received regorafenib plus PD-1 inhibitors or regorafenib alone as a later-line therapy from May 2019 to January 2022. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria, and safety was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: A total of 133 patients were included in the study (regardless of first-line treatment), including 94 who received regorafenib plus PD-1 inhibitors and 39 who received regorafenib. The regorafenib plus PD-1 inhibitors group had a significantly higher ORR (25.53% vs. 10.26%, P=0.015), higher DCR (87.23% vs. 66.67%, P=0.006), and longer PFS (median 9.0 vs. 4.0 months, P<0.0001) than the regorafenib group. Meanwhile, the median OS (mOS) did not differ between the regorafenib plus PD-1 and regorafenib monotherapy groups {mOS, 14.0 months [95% confidence interval (CI), 14.0-16.0 months] vs. 12.0 months (95% CI, 10.0-22.0 months)}. There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (71.79% vs. 78.72%, P=0.39) and the incidence of grade 3/4 serious adverse effects (5.13% vs. 18.09%, P=0.19) between the regorafenib monotherapy group and PD-1 inhibitors combination group. Conclusions: Compared with regorafenib alone, regorafenib combined with PD-1 inhibitors therapy increased PFS, ORR but did not improve OS, and can be used an option in second-line HCC therapy, regardless of first-line treatments. Regorafenib combined with PD-1 inhibitors is recommended as early as a second-line therapy to benefit patients. The combination regimen was as safe as regorafenib monotherapy for treatment of HCC in patients with compensated liver disease [Child-Turcotte-Pugh (CTP) A/B].

Vapor heat treatment against Planococcus lilacinus Cockerell (Hemiptera:Pseudococcidae) on dragon fruit.

BACKGROUND: The coffee mealybug Planococcus lilacinus Cockerell, is an invasive pest that infests dragon fruit [Selenicereus undatus (Haworth) D.R. Hunt], that may require a phytosanitary treatment to meet quarantine requirements. In this study, vapor heat treatment was conducted to disinfest P. lilacinus on dragon fruit and the quality of dragon fruit was evaluated thereafter. RESULTS: Adult female P. lilacinus was the most heat-tolerant stage at 47, 48 and 49 °C. The death kinetic model and probit model were used to predict LT99.9968 at the three temperatures. The treatment times predicted by the kinetic model that could effectively disinfest adult female P. lilacinus females were 120.84, 78.06 and 67.96 min at 47, 48 and 49 °C, respectively. In a confirmatory test of vapor heat treatment at 49 °C for 70 min, complete mortality was recorded for 33 195 adult females infesting 148 dragon fruits; thus, the efficacy level of disinfestation was 99.9910% at 95% confidence level. The quality of dragon fruit generally was not affected by heat treatment, fruit firmness was increased remarkably and respiration rate was significantly decreased. CONCLUSION: Our result indicates that vapor heat treatment at 49 °C for a duration of 70 min is an effective phytosanitary treatment for control of P. lilacinus on dragon fruit that minimally impacts fruit quality. © 2021 Society of Chemical Industry.

Genus Tetrastigma: A review of its folk uses, phytochemistry and pharmacology.

The genus Tetrastigma belongs to the Vitaceae family and contains over 100 species. This paper reviewed folk uses, chemical constituents, pharmacological activities, and clinical applications of the medicinal plants in the genus Tetrastigma. In addition, the paper also discussed the current problems for the further studies. Up to now, more than 240 compounds were reported from the genus Tetrastigma, covering 74 flavonoids, 14 terpenoids, 19 steroids, 21 phenylpropanoids, 14 alkaloids and others constituents. Among them, flavonoids are the major and the characteristic chemical constituents in this genus. Modern pharmacological studies and clinical practice showed that the extracts and chemical constituents of Tetrastigma species possessed wide pharmacological activities including antitumor, antioxidative, hepatoprotective, antiviral, anti-inflammatory, and analgesic activities. The information summarized in this paper provides valuable clues for new drug discovery and an incentive to expand the research of genus Tetrastigma.

Sesquiterpenes from Kadsura coccinea attenuate rheumatoid arthritis-related inflammation by inhibiting the NF-κB and JAK2/STAT3 signal pathways.

The roots of Kadsura coccinea is commonly used in Tujia ethnomedicine, named "heilaohu", having the effect of treating rheumatic arthritis (RA). Chemical investigation on the ethanol extract of heilaohu led to the isolation of one undescribed cuparane sesquiterpenoid, heilaohusesquiterpenoid A, one undescribed carotane sesquiterpenoids, heilaohusesquiterpenoid B, and eighteen sesquiterpene derivatives. Their structures were subsequently determined based on their 1D and 2D-NMR, HR-ESI-MS, and ECD spectroscopic data. Gaultheriadiolide was the most cytotoxic compound against the proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells with an IC50 value of 9.37 µM. In the same line, nine compounds exhibited significant inhibition effects against TNF-α and IL-6 release in the LPS-induced RAW264.7 cells with IC50 values ranging between 1.03 and 10.99 µM. The potential molecular mechanisms of the active compounds against RA were established through pharmacological network analysis based on the initial screening results. Experimental validation showed that gaultheriadiolide suppressed inflammation by inhibiting the NF-kB and JAK2/STAT3 pathways. This study enriches the structural diversity of sesquiterpenes in K. coccinea and lays a foundation for further anti-RA and anti-inflammatory studies.

Biomimetic Hybrid Membrane-Coated Xuetongsu Assisted with Laser Irradiation for Efficient Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a systemic autoimmune disease underlying a cascade of chronic inflammatory processes. Over the past decades, the response rate of effective RA treatments has remained scarce despite numerous advancements in the current therapeutic interventions, owing largely to the associated off-target adverse events and poor accumulation in the inflamed joints. Recently, there is a high interest in the development of targeted drug delivery system by using nanotechnology, as it can provide a handle to improve the therapy efficacy of RA. Here, multifunctional HA@RFM@PB@SE nanoparticles (HRPS NPs) are developed by loading schisanlactone E (SE, also called with xuetongsu), an anti-RA compound isolated from Tujia ethnomedicine xuetong, into Prussian blue nanoparticles (PB NPs) and further camouflage of RBC-RAFLS hybrid membrane with HA modification onto PB@SE NPs (PS NPs). We demonstrated that the modification of RFM makes PB NPs ideal decoys for targeting inflammatory mediators of arthritis due to the homing effects of the parental cells. Moreover, the encapsulation of RFM on the PB@SE NPs extended the blood circulation time and improved its targeting ability, which accordingly achieved optimal accumulation of SE in arthritic rat paws. In vitro and in vivo assay demonstrated the outstanding performance of HRPS NPs for synergistic chemo-/photothermal therapy of RA without side effects to healthy tissues. Molecular mechanism exploration indicated that the ultrastrong inhibition of synovial hyperplasia and bone destruction was partly via suppressing NF-κB signaling pathway and the expression of matrix metalloproteinases. In summary, the nanodrug delivery system showed controllable release behavior, targeted accumulation at arthritic sites and systemic regulation of immunity, hence improved therapeutic efficacy and clinical outcomes of the disease without attenuating safety.

Development and Validation of a nomogram for forecasting survival of alcohol related hepatocellular carcinoma patients.

Background: With the increasing incidence and prevalence of alcoholic liver disease, alcohol-related hepatocellular carcinoma has become a serious public health problem worthy of attention in China. However, there is currently no prognostic prediction model for alcohol-related hepatocellular carcinoma. Methods: The retrospective analysis research of alcohol related hepatocellular carcinoma patients was conducted from January 2010 to December 2014. Independent prognostic factors of alcohol related hepatocellular carcinoma were identified by Lasso regression and multivariate COX proportional model analysis, and the nomogram model was constructed. The reliability and accuracy of the model were assessed using the concordance index(C-Index), receiver operating characteristic (ROC) curve and calibration curve. Evaluate the clinical benefit and application value of the model through clinical decision curve analysis (DCA). The prognosis was assessed by the Kaplan-Meier (KM) survival curve. Results: In sum, 383 patients were included in our study. Patients were stochastically assigned to training cohort (n=271) and validation cohort (n=112) according to 7:3 ratio. The predictors included in the nomogram were splenectomy, platelet count (PLT), creatinine (CRE), Prealbumin (PA), mean erythrocyte hemoglobin concentration (MCHC), red blood cell distribution width (RDW) and TNM. Our nomogram demonstrated excellent discriminatory power (C-index) and good calibration at 1-year, 3-year and 5- year overall survival (OS). Compared to TNM and Child-Pugh model, the nomogram had better discriminative ability and higher accuracy. DCA showed high clinical benefit and application value of the model. Conclusion: The nomogram model we established can precisely forcasting the prognosis of alcohol related hepatocellular carcinoma patients, which would be helpful for the early warning of alcohol related hepatocellular carcinoma and predict prognosis in patients with alcoholic hepatocellular carcinoma.