Accurate measurement of Soret coefficients in binary hydrocarbons mixtures based on composite methods.

The Soret effect is a significant factor in various scenarios, with thermodiffusion in binary systems serving as a common method for the study. Most research focuses rarely on the distribution characteristics of components in diffusion systems; and Soret coefficients in the porous media could not be obtained by typical methods based on the thermodiffusion column, which are particularly important in the field of oil and gas development. Moreover, experiments on ground conditions have struggled to determine the Soret coefficient accurately due to the convective effect caused by gravity differentiation. The thermodiffusion behavior of n-pentane (C5) and n-heptane (C7) binary mixtures in both bulk and porous media conditions have been investigated, aiming to provide corrected coefficients that mitigate the influence of gravity using theoretical derivation. A new method was proposed to calculate the Soret coefficients in this work by establishing a model based on gas chromatography technology. Dynamic variation of component concentration along the path was studied, and the corresponding Soret coefficients were calculated and analyzed in parallel. The results indicate that the concentration and temperature exhibit a logarithmic relationship with the distance from the heat source. The Soret coefficient values obtained from measurements in porous media are closer to the theoretically corrected values, which do not account for gravity effects. Additionally, as the permeability decreases, the counteracting effect of porous media on convection becomes more pronounced. Therefore, it presents a novel method for accurately measuring the Soret coefficient that ignores convection to some extent.

HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing.

Hepatocellular carcinoma (HCC) acquires an immunosuppressive microenvironment, leading to unbeneficial therapeutic outcomes. Hyaluronan-mediated motility receptor (HMMR) plays a crucial role in tumor progression. Here, we found that aberrant expression of HMMR could be a predictive biomarker for the immune suppressive microenvironment of HCC, but the mechanism remains unclear. We established an HMMR-/- liver cancer mouse model to elucidate the HMMR-mediated mechanism of the dysregulated "don't eat me" signal. HMMR knockout inhibited liver cancer growth and induced phagocytosis. HMMRhigh liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMRhighCD47high expression showed a worse prognosis than those with HMMRlowCD47low expression. HMMR formed a complex with FAK/SRC in the cytoplasm to activate NF-κB signaling, which could be independent of membrane interaction with CD44. Notably, targeting HMMR could enhance anti-PD-1 treatment efficiency by recruiting CD8+ T cells. Overall, our data revealed a regulatory mechanism of the "don't eat me" signal and knockdown of HMMR for enhancing anti-PD-1 treatment.

The complete degradation of 1,2-dichloroethane in Escherichia coli by metabolic engineering.

1,2-Dichloroethane (1,2-DCA), a widely utilized chemical intermediate and organic solvent in industry, frequently enters the environment due to accidental leaks and mishandling during application processes. Thus, the in-situ remediation of contaminated sites has become increasingly urgent. However, traditional remediation methods are inefficient and costly, while bioremediation presents a green, efficient, and non-secondary polluting alternative. In this study, an engineered strain capable of completely degrading 1,2-DCA was constructed. We introduced six exogenous genes of the 1,2-DCA degradation pathway into E. coli and confirmed their normal transcription and efficient expression in this engineered strain through qRT-PCR and proteomics. The degradation experiments showed that the strain completely degraded 2 mM 1,2-DCA within 12 h. Furthermore, the results of isotope tracing verified that the final degradation product, malic acid, entered the tricarboxylic acid cycle (TCA) of E. coli and was ultimately fully metabolized. Also, morphological changes in the engineered strain and control strain exposed to 1,2-DCA were observed under SEM, and the results revealed that the engineered strain is more tolerant to 1,2-DCA than the control strain. In conclusion, this study paved a new way for humanity to deal with the increasingly complex environmental challenges.

Multilocus Phylogeny and Characterization of Five Undescribed Aquatic Carnivorous Fungi (Orbiliomycetes).

The diversity of nematode-trapping fungi (NTF) holds significant theoretical and practical implications in the study of adaptive evolution and the bio-control of harmful nematodes. However, compared to terrestrial ecosystems, research on aquatic NTF is still in its early stages. During a survey of NTF in six watersheds in Yunnan Province, China, we isolated 10 taxa from freshwater sediment. Subsequent identification based on morphological and multigene (ITS, TEF1-α, and RPB2) phylogenetic analyses inferred they belong to five new species within Arthrobotrys. This paper provides a detailed description of these five novel species (Arthrobotrys cibiensis, A. heihuiensis, A. jinshaensis, A. yangbiensis, and A. yangjiangensis), contributing novel insights for further research into the diversity of NTF and providing new material for the biological control of aquatic harmful nematodes. Additionally, future research directions concerning aquatic NTF are also discussed.

Creation of Environmentally Friendly Super "Dinitrotoluene Scavenger" Plants.

Pervasive environmental contamination due to the uncontrolled dispersal of 2,4-dinitrotoluene (2,4-DNT) represents a substantial global health risk, demanding urgent intervention for the removal of this detrimental compound from affected sites and the promotion of ecological restoration. Conventional methodologies, however, are energy-intensive, susceptible to secondary pollution, and may inadvertently increase carbon emissions. In this study, a 2,4-DNT degradation module is designed, assembled, and validated in rice plants. Consequently, the modified rice plants acquire the ability to counteract the phytotoxicity of 2,4-DNT. The most significant finding of this study is that these modified rice plants can completely degrade 2,4-DNT into innocuous substances and subsequently introduce them into the tricarboxylic acid cycle. Further, research reveals that the modified rice plants enable the rapid phytoremediation of 2,4-DNT-contaminated soil. This innovative, eco-friendly phytoremediation approach for dinitrotoluene-contaminated soil and water demonstrates significant potential across diverse regions, substantially contributing to carbon neutrality and sustainable development objectives by repurposing carbon and energy from organic contaminants.

Metabolic engineering of Escherichia coli for 2,4-dinitrotoluene degradation.

2,4-Dinitrotoluene (2,4-DNT) as a common industrial waste has been massively discharged into the environment with industrial wastewater. Due to its refractory degradation, high toxicity, and bioaccumulation, 2,4-DNT pollution has become increasingly serious. Compared with the currently available physical and chemical methods, in situ bioremediation is considered as an economical and environmentally friendly approach to remove toxic compounds from contaminated environment. In this study, we relocated a complete degradation pathway of 2,4-DNT into Escherichia coli to degrade 2,4-DNT completely. Eight genes from Burkholderia sp. strain were re-synthesized by PCR-based two-step DNA synthesis method and introduced into E. coli. Degradation experiments revealed that the transformant was able to degrade 2,4-DNT completely in 12 h when the 2,4-DNT concentration reached 3 mM. The organic acids in the tricarboxylic acid cycle were detected to prove the degradation of 2,4-DNT through the artificial degradation pathway. The results proved that 2,4-DNT could be completely degraded by the engineered bacteria. In this study, the complete degradation pathway of 2,4-DNT was constructed in E. coli for the first time using synthetic biology techniques. This research provides theoretical and experimental bases for the actual treatment of 2,4-DNT, and lays a technical foundation for the bioremediation of organic pollutants.

Effect of Discharge Voltage on the Microstructure of Graphene/PEKK Composite Samples by Electromagnetic Powder Molding.

The light weight, electrical conductivity, environmental friendliness, and high mechanical properties of graphene/PEKK composites make them popular in biomedical, electronic component and aerospace fields. However, the compaction density and carbonization of the specimen influence the microstructure and conductivity of the graphene/PEKK composite prepared by in situ polymerization, so electromagnetic-assisted molding was used to manufacture products to avoid carbonization and enhance the compaction density. The effects of different discharge voltages on the microstructure of the formed graphene/PEKK specimens were compared. Increasing the discharge voltage will lead to a closer distribution of flake graphene in the matrix to improve the compaction density, mechanical performance and conductivity. At the same time, the numerical analysis model was validated by comparison with the compaction density of the experimental results. Based on this research, the stress/strain distribution on the specimen was obtained with increasing discharge voltages.

Effect of betanin synthesis on photosynthesis and tyrosine metabolism in transgenic carrot.

BACKGROUND: Betalain is a natural pigment with important nutritional value and broad application prospects. Previously, we produced betanin biosynthesis transgenic carrots via expressing optimized genes CYP76AD1S, cDOPA5GTS and DODA1S. Betanin can accumulate throughout the whole transgenic carrots. But the effects of betanin accumulation on the metabolism of transgenic plants and whether it produces unexpected effects are still unclear. RESULTS: The accumulation of betanin in leaves can significantly improve its antioxidant capacity and induce a decrease of chlorophyll content. Transcriptome and metabolomics analysis showed that 14.0% of genes and 33.1% of metabolites were significantly different, and metabolic pathways related to photosynthesis and tyrosine metabolism were markedly altered. Combined analysis showed that phenylpropane biosynthesis pathway significantly enriched the differentially expressed genes and significantly altered metabolites. CONCLUSIONS: Results showed that the metabolic status was significantly altered between transgenic and non-transgenic carrots, especially the photosynthesis and tyrosine metabolism. The extra consumption of tyrosine and accumulation of betanin might be the leading causes.

Morphological and Phylogenetic Characterization of Five Novel Nematode-Trapping Fungi (Orbiliomycetes) from Yunnan, China.

Nematode-trapping fungi are widely studied due to their unique morphological structure, survival strategy, and potential value in the biological control of harmful nematodes. During the identification of carnivorous fungi preserved in our laboratory, five novel nematode-trapping fungi were established and placed in the genera Arthrobotrys and Drehslerella based on morphological and multigene (ITS, TEF, and RPB2) phylogenetic analyses. A. hengjiangensis sp. nov. and A. weixiensis sp. nov. are characterized by producing adhesive networks to catch nematodes. Dr. pengdangensis sp. nov., Dr. tianchiensis sp. nov., and Dr. yunlongensis sp. nov. are characterized by producing constricting rings. Morphological descriptions, illustrations, taxonomic notes, and phylogenetic analysis are provided for all new taxa; a key for Drechslerella species is listed; and some deficiencies in the taxonomy and evolution study of nematode-trapping fungi are also discussed herein.

Elevated NOX4 promotes tumorigenesis and acquired EGFR-TKIs resistance via enhancing IL-8/PD-L1 signaling in NSCLC.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been widely used for human non-small-cell lung cancer (NSCLC) treatment. However, acquired resistance to EGFR-TKIs is the major barrier of treatment success, and new resistance mechanism remains to be elucidated. In this study, we found that elevated NADPH oxidase 4 (NOX4) expression was associated with acquired EGFR-TKIs resistance. Gefitinib is the first-generation FDA-approved EGFR-TKI, and osimertinib is the third-generation FDA-approved EGFR-TKI. We demonstrated that NOX4 knockdown in the EGFR-TKI resistant cells enabled the cells to become sensitive to gefitinib and osimertinib treatment, while forced expression of NOX4 in the sensitive parental cells was sufficient to induce resistance to gefitinib and osimertinib in the cells. To elucidate the mechanism of NOX4 upregulation in increasing TKIs resistance, we found that knockdown of NOX4 significantly down-regulated the expression of transcription factor YY1. YY1 bound directly to the promoter region of IL-8 to transcriptionally activate IL-8 expression. Interestingly, knockdown of NOX4 and IL-8 decreased programmed death ligand 1 (PD-L1) expression, which provide new insight on TKIs resistance and immune escape. We found that patients with higher NOX4 and IL-8 expression levels showed a shorter survival time compared to those with lower NOX4 and IL-8 expression levels in response to the anti-PD-L1 therapy. Knockdown of NOX4, YY1 or IL-8 alone inhibited angiogenesis and tumor growth. Furthermore, the combination of NOX4 inhibitor GKT137831 and gefitinib had synergistic effect to inhibit cell proliferation and tumor growth and to increase cellular apoptosis. These findings demonstrated that NOX4 and YY1 were essential for mediating the acquired EGFR-TKIs resistance. IL-8 and PD-L1 are two downstream targets of NOX4 to regulate TKIs resistance and immunotherapy. These molecules may be used as potential new biomarkers and therapeutic targets for overcoming TKIs resistance in the future.

Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma.

Neoadjuvant chemoimmunotherapy (NACI) has shown promise in the treatment of resectable esophageal squamous cell carcinoma (ESCC). The microbiomes of patients can impact therapy response, and previous studies have demonstrated that intestinal microbiota influences cancer immunotherapy by activating gut immunity. Here, we investigated the effects of intratumoral microbiota on the response of patients with ESCC to NACI. Intratumoral microbiota signatures of ß-diversity were disparate and predicted the treatment efficiency of NACI. The enrichment of Streptococcus positively correlated with GrzB+ and CD8+ T-cell infiltration in tumor tissues. The abundance of Streptococcus could predict prolonged disease-free survival in ESCC. Single-cell RNA sequencing demonstrated that responders displayed a higher proportion of CD8+ effector memory T cells but a lower proportion of CD4+ regulatory T cells. Mice that underwent fecal microbial transplantation or intestinal colonization with Streptococcus from responders showed enrichment of Streptococcus in tumor tissues, elevated tumor-infiltrating CD8+ T cells, and a favorable response to anti-PD-1 treatment. Collectively, this study suggests that intratumoral Streptococcus signatures could predict NACI response and sheds light on the potential clinical utility of intratumoral microbiota for cancer immunotherapy. SIGNIFICANCE: Analysis of intratumoral microbiota in patients with esophageal cancer identifies a microbiota signature that is associated with chemoimmunotherapy response and reveals that Streptococcus induces a favorable response by stimulating CD8+ T-cell infiltration. See related commentary by Sfanos, p. 2985.

Released dsDNA-triggered inflammasomes serve as intestinal radioprotective targets.

Objectives: Intestinal mucositis is the major side effect during abdominal or pelvic radiotherapy, but the underlying immunogen remains to be further characterised and few radioprotective agents are available. This study investigated the role of dsDNA-triggered inflammasomes in intestinal mucositis during radiotherapy. Methods: Pro-inflammatory cytokines were detected by ELISA. Radiation-induced intestinal injury in mice was analyzed by means of survival curves, body weight, HE staining of intestines, and intestinal barrier integrity. Western blot, immunofluorescence staining, co-immunoprecipitation assay and flow cytometry were used to investigate the regulatory role of dsDNA on inflammasomes. Results: Here, we show that a high level of IL-1ß and IL-18 is associated with diarrhoea in colorectal cancer (CRC) patients during radiotherapy, which accounts for intestinal radiotoxicity. Subsequently, we found that the dose-dependently released dsDNA from the intestinal epithelial cells (IECs) serves as the potential immunogenic molecule for radiation-induced intestinal mucositis. Our results further indicate that the released dsDNA transfers into the macrophages in an HMGB1/RAGE-dependent manner and then triggers absent in melanoma 2 (AIM2) inflammasome activation and the IL-1ß and IL-18 secretion. Finally, we show that the FDA-approved disulfiram (DSF), a newly identified inflammasome inhibitor, could mitigate intestinal radiotoxicity by controlling inflammasome. Conclusion: These findings indicate that the extracellular self-dsDNA released from the irradiated IECs is a potential immunogen to stimulate immune cells and trigger the subsequent intestinal mucositis, while blunting the dsDNA-triggered inflammasome in macrophages may represent an exciting therapeutic strategy for side effects control during abdominal radiotherapy.

Squamous cell lung carcinoma with gastrointestinal metastasis: a case report and review of literature.

Squamous cell lung carcinoma (LUSC) originates from squamous cells and has a high rate of metastasis and recurrence. The lack of effective genetic targets and specific therapies has resulted in a poor prognosis for patients with LUSC. Gastrointestinal metastasis of LUSC is a rare occurrence in clinical practice. Patients with gastrointestinal metastasis usually have worse overall survival and the process of diagnosis is more complicated than those with metastasis elsewhere. What's more, there are no helpful guidelines for treating patients with a clinically confirmed diagnosis of gastrointestinal metastasis, which means the treatment method is limited. Here, we review the clinical features, diagnosis, and treatment of LUSC patients with gastrointestinal metastasis and report a rare case of LUSC accompanied by gastrointestinal metastasis. The patient was admitted to the hospital with coughing and hemoptysis. A tumor was found in his lung, and lesions were initially controlled with standard treatment. The patient's tumor re-occurred again shortly for which treatment was lacking. Without effective treatment methods, the disease was difficult to control. Our learnings from the case demonstrate that LUSC metastasizes to secondary lymphoid organs of the gastrointestinal tract, usually with a poor prognosis.

Arthrobotrys blastospora sp. nov. (Orbiliomycetes): A Living Fossil Displaying Morphological Traits of Mesozoic Carnivorous Fungi.

The evolution of carnivorous fungi in deep time is still poorly understood as their fossil record is scarce. The approximately 100-million-year-old Cretaceous Palaeoanellus dimorphus is the earliest fossil of carnivorous fungi ever discovered. However, its accuracy and ancestral position has been widely questioned because no similar species have been found in modern ecosystems. During a survey of carnivorous fungi in Yunnan, China, two fungal isolates strongly morphologically resembling P. dimorphus were discovered and identified as a new species of Arthrobotrys (Orbiliaceae, Orbiliomycetes), a modern genus of carnivorous fungi. Phylogenetically, Arthrobotrys blastospora sp. nov. forms a sister lineage to A. oligospora. A. blastospora catches nematodes with adhesive networks and produces yeast-like blastospores. This character combination is absent in all other previously known modern carnivorous fungi but is strikingly similar to the Cretaceous P. dimorphus. In this paper, we describe A. blastospora in detail and discuss its relationship to P. dimorphus.

Complete biodegradation of the oldest organic herbicide 2,4-Dichlorophenoxyacetic acid by engineering Escherichia coli.

After nearly 80 years of extensive application, the oldest organic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has caused many problems of environmental pollution and ecological deterioration. Bioremediation is an ideal method for pollutant treatment. However, difficult screening and preparation of efficient degradation bacteria have largely hindered its application in 2,4-D remediation. We have created a novel engineering Escherichia coli with a reconstructed complete degradation pathway of 2,4-D to solve the problem of screening highly efficient degradation bacteria in this study. The results of fluorescence quantitative PCR demonstrated that all nine genes in the degradation pathway were successfully expressed in the engineered strain. The engineered strains can quickly and completely degrade 0.5 mM 2, 4-D within 6 h. Inspiring, the engineered strains grew with 2,4-D as the sole carbon source. By using the isotope tracing method, the metabolites of 2,4-D were found incorporated into the tricarboxylic acid cycle in the engineering strain. Scanning electron microscopy showed that 2,4-D had less damage on the engineered bacteria than the wild-type strain. Engineered strain can also rapidly and completely remedy 2,4-D pollution in natural water and soil. Assembling the metabolic pathways of pollutants through synthetic biology was an effective method to create pollutant-degrading bacteria for bioremediation.

Downstaging and Conversation Strategy for Advanced Hepatocellular Carcinoma with Portal Vein Branch Tumor Thrombus: TACE, 125I Seed Implantation, and RFA for Hepatocellular Carcinoma with Portal Vein Branch Tumor Thrombus.

Background and Objectives: Trans-arterial chemoembolization (TACE) combined with 125I seed implantation is an effective treatment modality for hepatocellular carcinoma (HCC) with a portal vein tumor thrombus (PVTT). However, there are no reports on the effectiveness of radiofrequency ablation (RFA) after downstaging in such patients. This study aimed to investigate the efficacy and safety of TACE in combination with 125I seed implantation and RFA for the treatment of HCC complicated by PVTT. Methods: 49 patients diagnosed with HCC with PVTT between February 2015 and December 2016 were included. All patients were clinically or pathologically diagnosed with advanced HCC, intrahepatic lesions ≤3, and a single tumor diameter ≤70 mm, total diameter ≤100 mm. PVTT was limited to the unilateral portal vein branches. All the patients were treated with TACE combined with PVTT 125I seed implantation. The size and activity of intrahepatic lesions and PVTT were evaluated using enhanced magnetic resonance imaging 3 months after treatment, and other indicators were combined to determine the success of downstaging. Results: A total of 31 patients were successfully downstaged, while 18 patients did not achieve downstaging owing to the progression of intrahepatic lesions or PVTT activity/progression, the success rate of the downstaging was 63.27%. All 31 patients with successful downstaging underwent RFA for intrahepatic lesions. The 1-, 2-, and 3-year survival rates were 90.3%, 80.6%, and 48.4%, respectively. The median overall survival was 36 months (95% CI: 24.7-47.3). Conclusion: 125I seed implantation in combination with TACE can effectively inactivate PVTT and achieve downstaging. Furthermore, the addition of RFA can significantly improve patient survival.

Genetic engineering of complex feed enzymes into barley seed for direct utilization in animal feedstuff.

Currently, feed enzymes are primarily obtained through fermentation of fungi, bacteria, and other microorganisms. Although the manufacturing technology for feed enzymes has evolved rapidly, the activities of these enzymes decline during the granulating process and the cost of application has increased over time. An alternative approach is the use of genetically modified plants containing complex feed enzymes for direct utilization in animal feedstuff. We co-expressed three commonly used feed enzymes (phytase, ß-glucanase, and xylanase) in barley seeds using the Agrobacterium-mediated transformation method and generated a new barley germplasm. The results showed that these enzymes were stable and had no effect on the development of the seeds. Supplementation of the basal diet of laying hens with only 8% of enzyme-containing seeds decreased the quantities of indigestible carbohydrates, improved the availability of phosphorus, and reduced the impact of animal production on the environment to an extent similar to directly adding exogenous enzymes to the feed. Feeding enzyme-containing seeds to layers significantly increased the strength of the eggshell and the weight of the eggs by 10.0%-11.3% and 5.6%-7.7% respectively. The intestinal microbiota obtained from layers fed with enzyme-containing seeds was altered compared to controls and was dominated by Alispes and Rikenella. Therefore, the transgenic barley seeds produced in this study can be used as an ideal feedstuff for use in animal feed.

Design and application analysis of public health emergency training based on instructional system design model / 中华医学教育探索杂志

Objective:In order to improve the staff's ability to deal with public health emergencies, a third-class hospital in Beijing has made efforts to improve the emergency response ability of all staff members to achieve zero infection, and to carry out vocational training and assessment of all staff.Methods:The instructional system design (ISD) model system is used to design the training course. The online learning, electronic examination paper assessment and on-site training of people in the hospital were analyzed by Excel and SPSS 22.0.Results:After training, the average scores of trainees increased from 84 points to 100 points, and the average answering time was shortened from 308 s to 179 s. There were differences in the assessment scores before and after training for personnel with different professional titles, and there were differences in the assessment scores before and after training for personnel between different departments.Conclusion:In case of public health emergency, it is necessary to train and assess the whole staff. The application of ISD model is helpful to make training plan quickly. The application of online learning assessment is the first effective way of emergency training.

Prospective study of TACE combined with sorafenib vs TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma with portal vein tumor thrombus and arterioportal fistulas.

Purpose: To compare the efficacy of TACE combined with sorafenib and TACE combined with 125I seed implantation in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) combined with arterioportal fistulas (APFs), and discuss the efficacy and safety of TACE combined with 125I seed implantation. Patients and methods: Between January 2017 and December 2018, the clinical data of patients with HCC complicated with PVTT and APFs who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, First Affiliated Hospital of Zhengzhou University, and Henan Provincial People's Hospital were prospectively collected. The patients were divided into the TACE+sorafenib (TACE-S) group based on their treatment willingness. There were 26 and 32 patients in the TACE-S and TACE-125I groups, respectively. Both groups of patients underwent APFs occlusion during TACE therapy. The embolization effect of APFs was observed and recorded in the two groups, the efficacy of intrahepatic lesions and PVTT was evaluated, and the effects of different treatment methods on the efficacy were analysed. Results: All patients completed the 3 months follow-up. The improvement rates of APFs in TACE-S and TACE-125I groups were 30.77% (8/26) and 68.75% (22/32), respectively, and difference was statistically significant (χ2 = 8.287, P=0.004). The median survival time of TACE-S and TACE-125I groups was 8.00 months and 12.8 months, respectively (χ2 = 7.106, P=0.008). Multivariate analysis showed that the PVTT subtype (IIa/IIb) and treatment method (TACE-S or TACE-125I) were independent factors affecting the recanalization of APFs in patients (P<0.05). Conclusion: For patients with HCC with PVTT and APFs, TACE combined with 125I seed implantation can effectively treat portal vein tumor thrombus, thereby reducing the recanalization of APFs and prolonging the survival time of patients.

Transarterial chemoembolization combined with apatinib with or without PD-1 inhibitors in BCLC stage C hepatocellular carcinoma: A multicenter retrospective study.

Objective: We evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with apatinib plus PD-1 inhibitors (TACE-AP) compared with TACE combined with apatinib (TACE-A) in patients with advanced hepatocellular carcinoma (HCC) and to explore the prognostic factors affecting patient survival. Methods: Data from patients with unresectable HCC who received TACE-AP or TACE-A from December 2018 to June 2021 were collected retrospectively. The main outcome of the study was overall survival (OS) and prognostic factors affecting survival, while the secondary outcomes were progression-free survival (PFS), the objective response rate (ORR), and treatment-related adverse events (TRAEs). Propensity score matching (PSM) analysis was used to reduce patient selection bias, and the random survival forest (RF) model was employed to explore prognostic factors affecting patient survival. Results: We enrolled 216 patients, including 148 and 68 patients in the TACE-A and TACE-AP groups, respectively. A total of 59 pairs of patients were matched using PSM analysis. Before and after PSM, the OS, PFS, and ORR in the TACE-AP group were significantly higher than in the TACE-A group (before, OS: 22.5 months vs. 12.8 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 63.2% vs. 34.5%, P < 0.001; after, OS: 22.5 months vs. 12.0 months, P < 0.001; PFS: 6.7 months vs. 4.3 months, P < 0.001; ORR: 62.7% vs. 30.5%, P = 0.003). Multivariate Cox regression and RF models before and after PSM analysis revealed that the main prognostic factors affecting survival were tumor number, portal vein tumor thrombus (PVTT) invasion, alpha-fetoprotein (AFP) levels, total bilirubin (TBIL) level, and treatment. There was no significant difference in TRAEs between the two groups (P > 0.05). Conclusion: Compared with TACE-A, TACE-AP significantly improved OS, PFS, and ORR in patients with advanced HCC. The number of tumors, PVTT invasion, AFP levels, TBIL level, and treatment were significant prognostic factors associated with patient survival. All observed TRAEs were mild and controllable.