Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China.

BACKGROUND: The region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China's Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China. METHODS: A total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach. RESULTS: Ranking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC. CONCLUSIONS: With Ningbo's strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Life-course obesity and heart failure: a two-sample Mendelian randomization study.

Heart failure is a multifaceted clinical syndrome, with obesity identified as a significant modifiable risk factor. This study employed a two-sample Mendelian randomization (MR) design, incorporating obesity data across life stages, to elucidate the causal link between obesity and heart failure. Data on heart failure from the 2023 Finngen database and genetic predictors of obesity from the IEU OpenGWAS project were analyzed using the IVW method, MR-Egger regression, weighted median, simple mode, weighted mode, and scatter plots. Heterogeneity was assessed with Cochran's Q test, and horizontal pleiotropy with MR-Egger intercept test. Sensitivity to single-nucleotide polymorphisms (SNPs) was tested via leave-one-out analysis, and funnel plots were utilized for visual inspection of horizontal pleiotropy. Statistical powers were also calculated. The MR analysis findings indicate a significant relationship between birth weight and the likelihood of developing heart failure (Odds Ratio [OR] 1.134, 95% Confidence Interval [CI] 1.033-1.245, P = 0.008). In addition, a heightened childhood BMI was found to be a significant predictor of heart failure risk (OR 1.307, 95% CI 1.144-1.494, P = 8.51E-05), as was childhood obesity (OR 1.123, 95% CI 1.074-1.173, P = 2.37E-07). Furthermore, adult BMI sex-combined exhibited a strong correlation with the risk of heart failure (OR 2.365, 95% CI 2.128-2.629, P = 1.91E-57). Sensitivity analyses provided further support for the reliability of these results, with no significant indication of horizontal pleiotropy observed. This study shows that obesity, including childhood obesity, is linked to a higher risk of heart failure. These findings highlight the urgent need for early weight management interventions in public health and clinical settings to reduce heart failure rates.

Ocotillol-Type Pseudoginsenoside-F11 Alleviates Lipopolysaccharide-Induced Acute Kidney Injury through Regulation of Macrophage Function by Suppressing the NF-κB/NLRP3/IL-1ß Signaling Pathway.

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. The inflammatory response is the fundamental pathologic alteration throughout AKI, regardless of the various causal factors. Macrophages are the main immune cells involved in the inflammatory microenvironment in AKI. Consequently, targeting macrophages might become a novel strategy for the treatment of AKI. In this study, we demonstrated that pseudoginsenoside-F11 (PF11), a distinctive component of Panax quinquefolius L., regulated macrophage function and protected renal tubular epithelial cells TCMK-1 from lipopolysaccharide (LPS) in vitro. PF11 also alleviated renal injuries in an LPS-induced AKI mouse model, decreased the levels of inflammatory cytokines, reduced macrophage inflammatory infiltration, and promoted the polarization of M1 macrophages to M2c macrophages with suppression of the nuclear factor-κB/NOD-like receptor thermal protein domain-associated protein 3/interleukin-1ß (NF-κB/NLRP3/IL-1ß) signaling pathway. To further investigate whether this nephroprotective effect of PF11 is mediated by macrophages, we performed macrophage depletion by injection of clodronate liposomes in mice. Macrophage depletion abolished PF11's ability to protect against LPS-induced kidney damage with downregulating the NF-κB/NLRP3/IL-1ß signaling pathway. In summary, this is the first study providing data on the efficacy and mechanism of PF11 in the treatment of AKI by regulating macrophage function.

Secreted Particle Information Transfer (SPIT) - A Cellular Platform for In Vivo Genetic Engineering.

A multitude of tools now exist that allow us to precisely manipulate the human genome in a myriad of different ways. However, successful delivery of these tools to the cells of human patients remains a major barrier to their clinical implementation. Here we introduce a new cellular approach for in vivo genetic engineering, Secreted Particle Information Transfer (SPIT) that utilizes human cells as delivery vectors for in vivo genetic engineering. We demonstrate the application of SPIT for cell-cell delivery of Cre recombinase and CRISPR-Cas9 enzymes, we show that genetic logic can be incorporated into SPIT and present the first demonstration of human cells as a delivery platform for in vivo genetic engineering in immunocompetent mice. We successfully applied SPIT to genetically modify multiple organs and tissue stem cells in vivo including the liver, spleen, intestines, peripheral blood, and bone marrow. We anticipate that by harnessing the large packaging capacity of a human cell's nucleus, the ability of human cells to engraft into patients' long term and the capacity of human cells for complex genetic programming, that SPIT will become a paradigm shifting approach for in vivo genetic engineering.

Evolving indications and surgical techniques for corneal transplantation at a tertiary eye care center in southern China.

BACKGROUND: This retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021. METHODS: The medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty. RESULTS: The total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002). CONCLUSIONS: The annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.

Risk prediction models for successful discontinuation in acute kidney injury undergoing continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is a commonly utilized treatment modality for individuals experiencing severe acute kidney injury (AKI). The objective of this research was to construct and assess prognostic models for the timely discontinuation of CRRT in critically ill AKI patients receiving this intervention. Data were collected retrospectively from the MIMIC-IV database (n = 758) for model development and from the intensive care unit (ICU) of Huzhou Central Hospital (n = 320) for model validation. Nine machine learning models were developed by utilizing LASSO regression to select features. In the training set, all models demonstrated an AUROC exceeding 0.75. In the validation set, the XGBoost model exhibited the highest AUROC of 0.798, leading to its selection as the optimal model for the development of an online calculator for clinical applications. The XGBoost model demonstrates significant predictive capabilities in determining the discontinuation of CRRT.

Caffeic acid ameliorates metabolic dysfunction-associated steatotic liver disease via alleviating oxidative damage and lipid accumulation in hepatocytes through activating Nrf2 via targeting Keap1.

Metabolic-associated steatotic liver disease (MASLD), known as non-alcoholic fatty liver disease (NAFLD) in the past, encompasses a range of liver pathological conditions marked by the excessive lipid accumulation. Consumption of coffee is closely associated with the reduced risk of MASLD. Caffeic acid (CA), a key active ingredient in coffee, exhibits notable hepatoprotective properties. This study aims to investigate the improvement of CA on MASLD and the engaged mechanism. Mice underwent a 12-week high-fat diet (HFD) regimen to induce MASLD, and liver pathology was assessed using hematoxylin-eosin (H&E) and oil red O (ORO) staining. Hepatic inflammation was evaluated by F4/80 and Ly6G immunohistochemistry (IHC) and myeloperoxidase (MPO) measurement. Pathways and transcription factors relevant to MASLD were analyzed by using microarray data from patients' livers. Oxidative damage was evaluated by detecting reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Co-immunoprecipitation (CoIP), cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) were used to validate the binding between CA and its target protein. CA significantly alleviated liver damage, steatosis and inflammatory injury, and reduced the elevated NAFLD activity score (NAS) in HFD-fed mice. Clinical data indicate that fatty acid metabolism and ROS generation are pivotal in MASLD progression. CA increased the expression of fibroblast growth factor 21 (FGF21), FGF receptor 1 (FGFR1) and ß-Klotho (KLB), and promoted fatty acid consumption. Additionally, CA mitigated oxidative stress injury and activated nuclear factor erythroid 2-related factor-2 (Nrf2). In primary hepatocytes isolated from Nrf2 knockout mice, CA's promotion on FGF21 release and inhibition on oxidative stress and lipotoxicity was disappeared. CA could directly bind to kelch-like ECH-associated protein 1 (Keap1) that is an Nrf2 inhibitor protein. This study suggests that CA alleviates MASLD by reducing hepatic lipid accumulation, lipotoxicity and oxidative damage through activating Nrf2 via binding to Keap1.

Comparative evaluation of two clinical sampling techniques for HPV detection in male genital sites: a randomized controlled study.

AIMS: The optimal sampling methods for detecting human papillomavirus (HPV) in male genital sites remain unclear. This study aimed to assess the performance, acceptability, and comfort of two sampling techniques for male genital HPV detection. METHODS AND RESULTS: A total of 490 men aged 18-45 were randomly assigned in a 1:1 ratio to undergo either the rub-brush (nail file followed by swab) or brush-only method (swab only) for sampling at external genitalia sites (PGS) and perineum/perianal (PA) sites. HPV distribution, specimen validity (ß-globin as a quality reference), and participant acceptability and comfort were evaluated between the two sampling methods. The brush-only method demonstrated non-inferiority in detecting 14 high-risk HPV types (16/18/31/33/35/39/45/51/52/56/58/59/66/68) compared to the rub-brush method in both PGS (18.9% vs. 16.9%) and PA (10.5% vs. 11.9%). Although no significant differences were observed in positive rates for other HPV types, the brush-only method had a significantly higher invalid rate in PA (8.5% vs. 1.5%). Approximately 85.0% of participants reported good acceptability and comfort with both sampling methods, regardless of anatomical sites. CONCLUSIONS: This study suggests comparable performance, acceptability and comfort between the two sampling techniques for HPV detection. However, the rub-brush method may offer an advantage in higher sample validity.

Advances in the selection and timing of postoperative radioiodine treatment in patients with differentiated thyroid carcinoma.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. Patients who receive systematic care typically have a better prognosis. RAI treatment plays a key role in eradicating any remaining thyroid lesions in DTC patients, hence decreasing the risk of distant metastases and cancer recurrence. As research continues to advance, RAI treatment is becoming more and more individualized. Because of the excellent prognosis for DTC patients, there is a relatively broad window for RAI treatment, making it easy to overlook when to receive RAI treatment. However, research on this issue can help patients with varying recurrence risk stratification make better decisions about when to begin RAI treatment following surgery, and physicians can schedule patients based on the severity of their disease. This will improve patient prognosis and lessen needless anxiety in addition to helping solve the problems of unjust healthcare resource distribution. In this review, we will mainly discuss the target population of RAI treatment as well as studies that examine the impact of RAI treatment timing on patient outcomes. In an effort to discourage DTC patients and physicians from selecting RAI therapy at random, we also review the possible negative effects of this treatment.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Structure, Property Optimization, and Adsorption Properties of N,N'-methylenebisacrylamide Cross-Linked Polyacrylic Acid Hydrogels under Different Curing Conditions.

In this study, polyacrylic acid hydrogels were prepared by modulating the cross-linking agent mass ratio using UV and heat curing methods. The structures and properties of the hydrogels were characterized and analyzed using Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis. The results showed that the mechanical properties of the hydrogels prepared through UV curing were better than those prepared through heat curing. The maximum mechanical tensile strength of 139 kPa was achieved at a cross-linking agent mass ratio of 3.85% with 20 min of UV curing, and the maximum mechanical compressive strength of 0.16 MPa was achieved at a cross-linking agent mass ratio of 2.91% with 20 min of UV curing. However, the hydrogels prepared by heat curing had a higher tensile strength than those prepared using the heat curing method. In addition, the thermally cured hydrogels had higher water absorption and adsorption properties. Moreover, the PAA hydrogels prepared at cross-linking agent mass ratios of 1.91 and 2.91% with 2 h of the heat curing method had the best swelling properties. Moreover, the increase in the cross-linker mass concentration led to a decrease in the pore size and porosity and to a more compact structure.

Large negative differential conductance and its transformation in a single radical molecule.

The discovery of negative differential conductance (NDC) in a single molecule and mechanism controlling this phenomenon are important for molecular electronics. We investigated the electronic properties of a typical radical molecule 3-carbamoyl-2,2,5,5-tetramethyl-3-pyrrolin-1-yloxy (CTPO) on an Au(111) surface using low-temperature scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy. Large NDC was observed in single CTPO molecules at the boundary of the crystal monolayer. The origin of observed NDC is revealed as the inelastic electron-phonon scattering during tunneling, and the strong spatial variation of the NDC over the single molecule illustrates the nature of the localized radical group. In addition, the NDC can be transformed into a positive differential conductance peak by tuning coupling strengths between different tunneling channels. An empirical multi-channel model has been developed to describe the competition between the valley-shaped NDC and peak-shaped positive differential conductance. The unique electronic property and giant conductance change observed in this radical molecule is valuable for designing novel molecular devices in the future.

[Effects of soil relative water content on growth characteristics of Armillaria spp. and seedling production of Gastrodia elata f. glauca].

The seedling survival rate, yield, and individual weight of Gastrodia elata is closely related to the soil relative water content(RWC) and the growth characteristics of the associated fungi Armillaria spp. This study explored the effects of the soil RWC on the growth characteristics of Armillaria spp. and the seedling production of G. elata f. glauca, aiming to provide guidance for breeding G. elata f. glauca and selecting elite strains of Armillaria. According to the growth characteristics on the medium for activation, thirty strains of Armillaria were classified into 4 clusters. Two strains with good growth indicators were selected from each cluster and cultiva-ted with immature tuber(Mima) and the branches of the broad-leaved trees in a water-controlled box. The results showed that the Armillaria clusters with uniaxial branches of rhizoid cords, such as clusters Ⅲ and Ⅳ, were excellent clusters in symbiosis with G. elata f. glauca. The soil RWC had significant effects on the growth characteristics of Armillaria strains and the seedling survival rate, yield, and individual weight of G. elata f. glauca. The growth characteristics of Armillaria strains and the seedling survival rate, yield, and individual weight of G. elata f. glauca in the case of the soil RWC being 75% were significantly better than those in the case of other soil RWC. Cultivating Mima with elite strains of Armillaria, together with branches of broad-leaved trees, in the greenhouses with the artificial control of the soil RWC, can achieve efficient seedling production and Mima utilization of G. elata f. glauca.

Divergent Synthesis of Enantioenriched Silicon-Stereogenic Benzyl-, Vinyl- and Borylsilanes via Asymmetric Aryl to Alkyl 1,5-Palladium Migration.

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

Analysis of the Volatile Components in Different Parts of Three Species of the Genus Amomum via Combined HS-SPME-GC-TOF-MS and Multivariate Statistical Analysis.

The study used headspace solid-phase microextraction coupled with gas chromatography-time-of-flight mass spectrometry (HS-SPME-GC-TOF-MS) to analyze volatile compounds in leaves and fruits of Amomum tsaoko, Amomum paratsaoko, and Amomum koenigii. The composition and aroma of distinct metabolites were analyzed using multivariate statistical methods. A total of 564 volatile compounds were identified from three species of the genus Amomum, which were further divided into nine categories: terpenoids, carboxylic acids, alcohols, hydrocarbons, aldehydes, ketones, phenols, ethers, and other compounds. Terpenoids and alcohols were the most abundant. The content and types of compounds vary in A. tsaoko, A. paratsaoko, and A. koenigii, so mixing or substituting them is not advisable. We selected 45 metabolites based on the criteria of the variable importance in projection values (VIP > 1.5) and one-way ANOVA (p < 0.05). The top 19 metabolites with the most significant VIP values were chosen. Interestingly, (Z)-2-decenal was only found in Amomum koenigii, while nitroethane and nonanal were only present in cultivated A. tsaoko. Additionally, linalool, cineole, and (D)-limonene were the main components affecting the aroma of three species of the genus Amomum. The volatile components identified in this study provide a theoretical basis for analyzing the unique flavor of A. tsaoko, A. paratsaoko, and A. koenigii.

Fabrication of Carbon Dots with Singlet Oxygen Generation and Their Potential Photodynamic Therapy Applications.

Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example, bioimaging, fluorescence sensing, and drug delivery, etc. Recently, it was found that, under light excitation, CDs can also be exploited as a novel photosensitizer to prepare reactive oxygen species (ROS), which expand their applications in the field of photodynamic therapy for cancer treatment. Nevertheless, the high cost and complex fabrication approach of CDs significantly limit their applications. To address this issue, bottom-up routes usually utilize sustainable and inexpensive carbon precursor as starting materials, employed N,N-dimethylformamide (DMF) or ethanol as an environmental-friendly solvent. Bottom-up approach was energy efficient, and the purification process was relatively simple by dialysis. Therefore, carbon dots (CDs) were facilely fabricated in a one-pot solvothermal process using 1-aminoanthraquinone as a precursor, and their application as photosensitizers for in vitro antitumor cells, especially photodynamic therapy (PDT) was established. Then the photophysical and nanoscale dimensions properties of the fabricated CDs were characterized via TEM, UV-visible, fluorescence, and FT-IR spectroscopy. The synthesized N-doped CDs can easily dissolve in water, possess very low biotoxicity, yellow-light emission (maximum peak at 587 nm). More importantly, PDT studies demonstrated that the obtained CDs possess a high singlet oxygen yield of 35%, and exhibit significant phototoxicity to cancer cells upon 635 nm laser irradiation. These studies highlight that N-doped CDs can be facilely synthesized from only one precursor, and are a potentially novel theranostic agent for in vivo PDT.

PKIB, a Novel Target for Cancer Therapy.

The serine-threonine kinase protein kinase A (PKA) is a cyclic AMP (cAMP)-dependent intracellular protein with multiple roles in cellular biology including metabolic and transcription regulation functions. The cAMP-dependent protein kinase inhibitor ß (PKIB) is one of three known endogenous protein kinase inhibitors of PKA. The role of PKIB is not yet fully understood. Hormonal signaling is correlated with increased PKIB expression through genetic regulation, and increasing PKIB expression is associated with decreased cancer patient prognosis. Additionally, PKIB impacts cancer cell behavior through two mechanisms; the first is the nuclear modulation of transcriptional activation and the second is the regulation of oncogenic AKT signaling. The limited research into PKIB indicates the oncogenic potential of PKIB in various cancers. However, some studies suggest a role of PKIB in non-cancerous disease states. This review aims to summarize the current literature and background of PKIB regarding cancer and related issues. In particular, we will focus on cancer development and therapeutic possibilities, which are of paramount interest in PKIB oncology research.

Corrigendum: Involvement of endoplasmic reticulum stress in trigeminal ganglion corneal neuron injury in dry eye disease.

[This corrects the article DOI: 10.3389/fnmol.2023.1083850.].

Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.

BACKGROUND: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. METHODS: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. RESULTS: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. CONCLUSIONS: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.