Relaxin combined with transarterial chemoembolization achieved synergistic effects and inhibited liver cancer metastasis in a rabbit VX2 model.

OBJECTIVE: To explore the effect and mechanism of relaxin (RLX) in the growth and metastasis of livercancer after combination treatment with transarterial chemoembolization (TACE). MATERIALS AND METHODS: HCCLM3 and Huh-7 cells were adopted to evaluate the effect of tumor proliferation, migration, and invasion after RLX administration in vitro. The rabbit VX2 model was used to evaluate the biosafety, doxorubicin penetration, local tumor response, tumor metastasis, and survival benefit of RLX combined with TACE treatment. RESULTS: RLX did not affect the proliferation, migration, or invasion of HCCLM3 and Huh-7 cells, and the expression of E-cadherin and HIF-1α also remained unchanged while the MMP-9 protein was upregulated in vitro. In the rabbit VX2 model, compared to the normal saline group (NS), RLX group (RLX) and TACE mono-therapy group (TACE), the group that received TACE combined with RLX (TACE + RLX) showed an improved local tumor response and survival benefit. Furthermore, TACE combined with RLX was found to reduce tumor metastasis. This combination therapy reduced the fibrotic extracellular matrix in the tumor microenvironment, allowing for better penetration of doxorubicin, improved infiltration of CD8+ T cells and affected the secretion of cytokines. Additionally, RLX combined with TACE was able to decrease the expression of HIF-1α and PD-L1. The biosafety of TACE combined with RLX was also confirmed. CONCLUSION: RLX synergized with TACE by mitigating the fibrotic extracellular matrix and tumor hypoxic microenvironment, improving the therapeutic effect and inhibiting metastasis during the treatment of liver cancer.

oHSV2-mGM repolarizes TAMs and cooperates with αPD1 to reprogram the immune microenvironment of residual cancer after radiofrequency ablation.

BACKGROUND: Due to the size and location of the tumor, incomplete radiofrequency ablation (iRFA) of the target tumor inhibits tumor immunity. In this study, a murine herpes simplex virus (oHSV2-mGM) armed with granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed to explore its effect on innate and adaptive immunity during iRFA, and the inhibitory effect of programmed cell death-1 (PD1) on tumor. METHODS: We verified the polarization and activation of RAW264.7 cells mediated by oHSV2-mGM in vitro. Subsequently, we evaluated the efficacy of oHSV2-mGM alone and in combination with αPD1 in the treatment of residual tumors after iRFA in two mouse models. RNA-seq was used to characterize the changes of tumor microenvironment. RESULTS: oHSV2-mGM lysate effectively stimulated RAW264.7 cells to polarize into M1 cells and activated M1 phenotypic function. In the macrophage clearance experiment, oHSV2-mGM activated the immune response of tumor in mice. The results in vivo showed that oHSV2-mGM showed better anti-tumor effect in several mouse tumor models. Finally, oHSV2-mGM combined with PD1 antibody can further enhance the anti-tumor effect of oHSV2-mGM and improve the complete remission rate of tumor in mice. CONCLUSION: The application of oHSV2-mGM leads to the profound remodeling of the immune microenvironment of residual tumors. oHSV2-mGM also works in synergy with PD1 antibody to achieve complete remission of tumors that do not respond well to monotherapy at immune checkpoints. Our results support the feasibility of recombinant oncolytic virus in the treatment of residual tumors after iRFA, and propose a new strategy for oncolytic virus treatment of tumors.

Experimental demonstration of wavefront reconstruction and correction techniques for variable targets based on distorted grating and deep learning.

This research presents a practical approach for wavefront reconstruction and correction adaptable to variable targets, with the aim of constructing a high-precision, general extended target adaptive optical system. Firstly, we delve into the detailed design of a crucial component, the distorted grating, simplifying the optical system implementation while circumventing potential issues in traditional phase difference-based collection methods. Subsequently, normalized fine features (NFFs) and structure focus features (SFFs) which both are independent of the imaging target but corresponded precisely to the wavefront aberration are proposed. The two features provide a more accurate and robust characterization of the wavefront aberrations. Then, a Noise-to-Denoised Generative Adversarial Network (N2D-GAN) is employed for denoising real images. And a lightweight network, Attention Mechanism-based Efficient Network (AM-EffNet), is applied to achieve efficient and high-precision mapping between features and wavefronts. A prototype of object-independent adaptive optics system is demonstrated by experimental setup, and the effectiveness of this method in wavefront reconstruction for different imaging targets has been verified. This research holds significant relevance for engineering applications of adaptive optics, providing robust support for addressing challenges within practical systems.

Multi-line-of-sight Hartmann-Shack wavefront sensing based on image segmentation and K-means sorting.

Multi-line-of-sight wavefront sensing, crucial for next-generation astronomy and laser applications, often increases system complexity by adding sensors. This research introduces, to the best of our knowledge, a novel method for multi-line-of-sight Hartmann-Shack wavefront sensing by using a single sensor, addressing challenges in centroid estimation and classification under atmospheric turbulence. This method contrasts with existing techniques that rely on multiple sensors, thereby reducing system complexity. Innovations include combining edge detection and peak extraction for precise centroid calculation, improved k-means clustering for robust centroid classification, and a centroid filling algorithm for subapertures with light loss. The method's effectiveness was confirmed through simulations for a five-line-of-sight system and experimental setup for two-line and three-line-of-sight systems, demonstrating its potential in real atmospheric aberration correction conditions. Experimental findings indicate that, when implemented in a closed-loop configuration, the method significantly reduces wavefront residuals from 1 λ to 0.1 λ under authentic atmospheric turbulence conditions. Correspondingly, the quality of the far-field spot is enhanced by a factor of 2 to 4. These outcomes collectively highlight the method's robust capability in enhancing optical system performance in environments characterized by genuine atmospheric turbulence.

Performance of the neural network-based prediction model in closed-loop adaptive optics.

Adaptive optics (AO) technology is an effective means to compensate for atmospheric turbulence, but the inherent delay error of an AO system will cause the compensation phase of the deformable mirror (DM) to lag behind the actual distortion, which limits the correction performance of the AO technology. Therefore, the feed-forward prediction of atmospheric turbulence has important research value and application significance to offset the inherent time delay and improve the correction bandwidth of the AO system. However, most prediction algorithms are limited to an open-loop system, and the deployment and the application in the actual AO system are rarely reported, so its correction performance improvement has not been verified in practice. We report, to our knowledge, the first successful test of a deep learning-based spatiotemporal prediction model in an actual 3 km laser atmospheric transport AO system and compare it with the traditional closed-loop control methods, demonstrating that the AO system with the prediction model has higher correction performance.

Earthworm gut digestion drives the transfer behavior of antibiotic resistance genes in layers of extracellular polymeric substances during vermicomposting of dewatered sludge.

Gut digestion by earthworms (GDE) is a crucial step in vermicomposting, affecting the fate of antibiotic resistance genes (ARGs) in vermicompost sludge. The extracellular polymeric substance (EPS) matrix of sludge is an important space for ARG transfer. However, the effect of GDE on EPS-associated ARGs remains unclear. Therefore, this study explored the role of GDE in driving the transfer of ARGs within different EPS layers in sludge. For this, the changes in intracellular ARGs and EPS-associated ARGs in sludge were analyzed after 5 days of the GDE process. The results showed that after the GDE process, both nitrate and dissolved organic carbon significantly increased in all EPS layers of sludge, while the proteins and polysaccharides only enhanced in soluble and loosely bound EPS of sludge. In addition, a 7.0% decrease in bacterial diversity was recorded after the GDE process, with a functional bacterial community structure emerging. Moreover, the absolute abundance of total ARGs and mobile genetic elements decreased by 90.71% and 61.83%, respectively, after the GDE process. Intracellular ARGs decreased by 92.1%, while EPS-associated ARGs increased by 4.9%, indicative of intracellular ARG translocation into the EPS during the GDE process. Notably, the ARGs exhibited significant enrichment in both the soluble and loosely bound EPS, whereas they were reduced in the tightly bound EPS. The structural equation modeling revealed that the GDE process effectively mitigated the ARG dissemination risk by modulating both the EPS structure and microenvironment, with the organic structure representing a primary factor influencing ARGs in the EPS.

Effect of metformin on hepatocellular carcinoma patients with type II diabetes receiving transarterial chemoembolization: a multicenter retrospective cohort study.

BACKGROUND: Diabetes is prevalent among patients with hepatocellular carcinoma (HCC) and is associated with a poor prognosis. Although the hypoglycemic drug metformin has shown anti-tumor effects, its potential positive effect on patients with HCC and diabetes undergoing transarterial chemoembolization (TACE) remains unclear. Therefore, this study aimed to investigate the efficacy and safety of metformin in patients with HCC and type II diabetes who are receiving TACE. MATERIALS AND METHODS: This retrospective study involved 372 consecutive patients with HCC and type II diabetes across three medical centers between January 2014 and June 2021. All patients underwent TACE. Propensity score matching (PSM) was used to reduce selection bias. Cox proportional hazards regression was employed to compare all-cause death between the metformin and non-metformin groups, while competing risk regression was performed to assess cancer-specific death. RESULTS: Among 372 patients included in the study, 208 patients (177 male patients and 31 female patients) with mean age 59.6 (10.3) years received metformin and 164 patients (139 male patients and 25 female patients) with mean age 60.3 (10.0) years did not. Before PSM, patients with metformin had significantly longer median overall survival (mOS) and median progression-free survival (mPFS) than those without metformin (mOS: 34 months, 95% CI: 25.6-42.4 vs. 20 months, 95% CI: 15.3-24.7; P<0.001; mPFS: 11 months, 95% CI: 9.3-12.7 vs. 8 months, 95% CI: 5.9-10.1; P<0.001). Similar results were observed after PSM. Multivariate regression analysis indicated that metformin was associated with a reduced risk of all-cause mortality (HR: 0.589, 95% CI: 0.454-0.763; P<0.001) and tumor progression (HR: 0.667, 95% CI: 0.526-0.845; P=0.001) before PSM. After excluding deaths related to other factors, metformin continued to demonstrate a reduction in cancer-specific mortality risk among the patients. Subgroup analysis further revealed that patients using metformin had lower all-cause mortality risk and tumor progression risk than those without metformin in most subgroups. Adverse event evaluation suggested that metformin could lead to elevated nausea incidence. CONCLUSION: Metformin may confer survival benefits to patients with HCC and type II diabetes undergoing TACE. Metformin may simultaneously address multiple aspects of treatment in these patients.

Ultrasmall Metal TPZ Complexes with Deep Tumor Penetration for Enhancing Radiofrequency Ablation Therapy and Inducing Antitumor Immune Responses.

Radiofrequency ablation (RFA) is one of the most common minimally invasive techniques for the treatment of solid tumors, but residual malignant tissues or small satellite lesions after insufficient RFA (iRFA) are difficult to remove, often leading to metastasis and recurrence. Here, Fe-TPZ nanoparticles are designed by metal ion and (TPZ) ligand complexation for synergistic enhancement of RFA residual tumor therapy. Fe-TPZ nanoparticles are cleaved in the acidic microenvironment of the tumor to generate Fe2+ and TPZ. TPZ, an anoxia-dependent drug, is activated in residual tumors and generates free radicals to cause tumor cell death. Elevated Fe2+ undergoes a redox reaction with glutathione (GSH), inducing a strong Fenton effect and promoting the production of the highly toxic hydroxyl radical (•OH). In addition, the ROS/GSH imbalance induced by this treatment promotes immunogenic cell death (ICD), which triggers the release of damage-associated molecular patterns, macrophage polarization, and lymphocyte infiltration, thus triggering a systemic antitumor immune response and noteworthy prevention of tumor metastasis. Overall, this integrated treatment program driven by multiple microenvironment-dependent pathways overcomes the limitations of the RFA monotherapy approach and thus improves tumor prognosis. Furthermore, these findings aim to provide new research ideas for regulating the tumor immune microenvironment.

In situ anchored ternary hierarchical hybrid nickel@cobaltous sulfide on poly(3,4-ethylenedioxythiophene)-reduced graphene oxide for highly efficient non-enzymatic glucose sensing.

A ternary hierarchical hybrid Ni@CoxSy/poly(3,4-ethylenedioxythiophene)-reduced graphene oxide (Ni@CoxSy/PEDOT-rGO) is rationally designed and in situ facilely synthesized as electrocatalyst to construct a binder-free sensing platform for non-enzymatic glucose monitoring through traditional electrodeposition procedure. The as-prepared Ni@CoxSy/PEDOT-rGO presents unique hierarchical structure and multiple valence states as well as strong and robust adhesion between Ni@CoxSy/PEDOT-rGO and GCE. Profiting from the aforementioned merits, the sensing platform constructed under optimal conditions achieved a wide detection range (0.2 µM ~ 2.0 mM) with high sensitivity (1546.32 µA cm-2 mM-1), a rapid response time (5 s), an ultralow detection limit (0.094 µM), superior anti-interference performance, excellent reproducibility and considerable stability. Furthermore, the sensor demonstrates an acceptable accuracy and appreciable recoveries ranging from 90.0 to 102.0% with less than 3.98% RSD in human blood serum samples, indicating the prospect of the sensor for the real samples analysis. It will provide a strategy to rationally design and fabricate ternary hierarchical hybrid as nanozyme for glucose assay.

Multiscale Static Compressive Damage Characteristics of Kiwifruit Based on the Finite Element Method.

In the handling or processing process, fruits are easily crushed by external loads. This type of damage in fruit often leads to the internal pulp browning and rotting, with the severity largely dependent on the fruit tissue's geometric and mechanical properties. In kiwifruits, with their thin skin and dark-colored flesh, it is particularly challenging to observe and analyze the damage caused by extrusion through traditional experimental methods. The objective of this research is to construct a multi-scale finite element model encompassing the skin, flesh, and core by measuring the geometric and mechanical properties of kiwifruit, to assess and predict the damage characteristics under compression, and to verify the accuracy of the finite element model through experiments. The results indicated that kiwifruits demonstrated different compressive strengths in different directions during compression. The compressive strength in the axial direction was higher than that in the radial direction, and there was little difference between the long and short radial directions. The flesh tissue is the most vulnerable to mechanical damage under external compression, followed by the core. At strain levels below 5%, there was no noticeable damage in the axial or radial directions of the kiwifruit. However, when strain exceeded 5%, damage began to manifest in some of the flesh tissue. To maintain fruit quality during storage and transportation, the stacking height should not exceed 77 fruits in the axial direction, 48 in the long direction, and 53 in the short direction. The finite element analysis showed that the established model can effectively simulate and predict the internal damage behavior of kiwifruits under compression loads, which is helpful for a deeper understanding of the mechanical properties of fruits and provides a theoretical basis and technical guidance for minimizing mechanical damage during fruit handling.

Highly Stable Spatio-Temporal Prediction Network of Wavefront Sensor Slopes in Adaptive Optics.

Adaptive Optics (AO) technology is an effective means to compensate for wavefront distortion, but its inherent delay error will cause the compensation wavefront on the deformable mirror (DM) to lag behind the changes in the distorted wavefront. Especially when the change in the wavefront is higher than the Shack-Hartmann wavefront sensor (SHWS) sampling frequency, the multi-frame delay will seriously limit its correction performance. In this paper, a highly stable AO prediction network based on deep learning is proposed, which only uses 10 frames of prior wavefront information to obtain high-stability and high-precision open-loop predicted slopes for the next six frames. The simulation results under various distortion intensities show that the prediction accuracy of six frames decreases by no more than 15%, and the experimental results also verify that the open-loop correction accuracy of our proposed method under the sampling frequency of 500 Hz is better than that of the traditional non-predicted method under 1000 Hz.

Object-independent wavefront sensing method based on an unsupervised learning model for overcoming aberrations in optical systems.

This Letter introduces the idea of unsupervised learning into object-independent wavefront sensing for the first time, to the best of our knowledge, which can achieve fast phase recovery of arbitrary objects without labels. First, a fine feature extraction method which only depends on the wavefront aberrations is proposed. Then, a lightweight neural network and an optical feature system are combined to form an unsupervised learning model, and the neural network is promoted to be well trained by reversely outputting fine features. Simulation results prove that the proposed method can effectively overcome the aberrations (static or variable) existing in the optical system and achieve wavefront sensing of different objects with high precision and efficiency.

Fabrication and Investigation of the Microwave Absorption of Nonwovens Modified by Carbon Nanotubes and Graphene Flakes.

This study aims to investigate the influences of carbon nanotubes (CNTs) and graphene flakes (GFs) on the microwave absorption performance of nonwovens. Nonwovens were modified with CNTs and GFs through an impregnation method, creating a series of absorption samples with different carbon nanomaterial contents. Then the absorption performance of the samples was tested on both sides in the X-band (8.2~12.4 GHz) and the Ku-band (12~18 GHz) using the arch method. The experimental results showed that the absorption performance of GF-impregnated nonwovens was superior to that of CNT-impregnated nonwovens, and the overall absorption performance in the Ku-band was better than in the X-band. At a CNT content of 5 wt.%, the reflection loss of the impregnated nonwovens on the backside reached a minimum of -14.06 dB and remained below -10 dB in the 17.42~17.88 GHz frequency range. The sample fabricated with 4 wt.% GFs in the impregnation solution exhibited the best absorption performance, with minimum reflection losses of -15.33 dB and -33.18 GHz in the X-band and Ku-band, respectively. When the GFs were at 3 wt.%, the absorption bandwidth below -10 dB reached 4.16 GHz. In contrast to CNT-impregnated nonwovens, the frontside of GF-impregnated nonwovens demonstrated better absorption performance in the Ku-band. The results of this work provide experimental data support for the fabrication and application of microwave absorption materials.

Association of the pretreatment lung immune prognostic index with immune checkpoint inhibitor outcomes in patients with advanced hepatocellular carcinoma.

OBJECTIVE: To evaluate whether the pretreatment Lung Immune Prognostic Index (LIPI) is associated with outcomes in advanced hepatocellular carcinoma (HCC) patients under ICI. METHODS: A two-center retrospective study of patients with HCC treated with immune checkpoint inhibitors (ICIs) between January 2018 and January 2021 was performed. Based on pretreatment derived neutrophils/ (leukocytes minus neutrophils) ratio (dNLR) greater than 3 and a lactate dehydrogenase (LDH) level greater than the normal value, patients were stratified into three groups (good LIPI:0 risk factor, intermediate LIPI: 1 risk factor, and poor LIPI: 2 risk factors). The primary endpoints were overall survival (OS) and progression-free survival (PFS). The second endpoints were disease control rate (DCR) and objective response rate (ORR). RESULTS: In the pooled cohort (n = 224), 80 (35.7%) had a good LIPI (zero factor), 91 (40.6%) had intermediate LIPI (one factor), and 53 (23.7%) had poor LIPI (two factors). The median follow-up was 25.1 months. Median OS was 16.8 months, 12.5 months, and 9.5 months for the good, intermediate, and poor LIPI groups, respectively (P < 0.0001). Median PFS was 11.8 months, 7.8 months, and 4.0 months for the good, intermediate, and poor LIPI groups, respectively (P < 0.0001). Multivariate analysis indicated that the intermediate LIPI and poor LIPI both were independently associated with OS, PFS, and ORR, DCR (P < 0.05), as risk factors. CONCLUSION: Pretreatment LIPI was correlated with worse outcomes for ICIs suggesting that LIPI could be promising biomarker for advanced HCC patients under ICIs.

Efficacy, mechanism, and safety of melatonin-loaded on thermosensitive nanogels for rabbit VX2 tumor embolization: A novel design.

Transarterial chemoembolization (TACE) has been widely used for hepatocellular carcinoma. Reducing hypoxia in the tumor microenvironment after TACE remains a challenge as tumor progression is common in post-TACE patients due to the hypoxic tumor microenvironment. In this study, melatonin loaded on p(N-isopropyl-acrylamide-co-butyl methylacrylate) (PIB-M) was used for tumor embolism. Two types of human hepatoma cell lines were used to explore the mechanism by which melatonin prevents the growth and metastasis of cancer cells in vitro. A VX2 rabbit tumor model was used to evaluate the efficacy, mechanism, and safety of PIB-M in vivo. We found that under hypoxic condition, melatonin could inhibit tumor cell proliferation and migration by targeting hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor A (VEGF-A) in vitro. In vivo, PIB-M inhibited tumor growth and metastasis in rabbit VX2 tumors by promoting apoptosis of tumor cells and targeting related angiogenic proteins and vascular permeability proteins. A high concentration of melatonin in the PIB-M group could be maintained in tumor tissue for 72 h after embolization. The liver and kidney functions were most damaged on the first day but recovered to normal on the seventh day after embolization in the PIB-M group. This novel method may open avenues for reduction of tumor growth and metastasis after TACE and is efficacy and safety, which may be used for treatment for other solid tumors and clinical translation.

Recent advances in oncolytic virus therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly refractory cancer and the fourth leading cause of cancer-related mortality worldwide. Despite the development of a detailed treatment strategy for HCC, the survival rate remains unsatisfactory. Oncolytic virus has been extensively researched as a new cancer therapeutic agent in the treatment of HCC. Researchers have designed a variety of recombinant viruses based on natural oncolytic diseases, which can increase the targeting of oncolytic viruses to HCC and their survival in tumors, as well as kill tumor cells and inhibit the growth of HCC through a variety of mechanisms. The overall efficacy of oncolytic virus therapy is known to be influenced by anti-tumor immunity, toxic killing effect and inhibition of tumor angiogenesis, etc. Therefore, a comprehensive review of the multiple oncolytic mechanisms of oncolytic viruses in HCC has been conducted. So far, a large number of relevant clinical trials are under way or have been completed, and some encouraging results have been obtained. Studies have shown that oncolytic virus combined with other HCC therapies may be a feasible method, including local therapy, chemotherapy, molecular targeted therapy and immunotherapy. In addition, different delivery routes for oncolytic viruses have been studied so far. These studies make oncolytic virus a new and attractive drug for the treatment of HCC.

The Feasibility of TACE Combined with TKIs Plus PD-1 Antibody for Advanced HCC.

Objective: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs: sorafenib, lenvatinib, and apatinib) plus camrelizumab (TACE-TKIs-C) vs TACE combined with TKIs (TACE-TKIs) for advanced hepatocellular carcinoma (HCC). Methods: In this two-center retrospective study, patients with advanced HCC treated with TACE-TKIs-C or TACE-TKIs were enrolled between January 1, 2018, to October 1, 2020. A total of 260 eligible patients received TACE-TKIs-C (N=70) or TACE-TKIs (N=190). The differences in overall survival (OS), progression-free survival (PFS) and tumor response were compared between two groups. Propensity score matching (PSM) analysis was applied to reduce patient selection bias. The risk factors affecting OS or PFS were analyzed. Results: Fifty-three pairs of patients were matched after PSM analysis. Before PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: not reached vs 12.0 months, P<0.0001; PFS: 10.0 months vs 6.0 months, P<0.0001). After PSM analysis, the median OS and PFS of TACE-TKIs-C were significantly longer than those of the TACE-TKIs (OS: Not reached vs 13.0 months, P<0.0001; PFS: 9.0 months vs 6.0 months, P<0.0001); the uni- and multivariate analysis revealed that TACE-TKIs-C treatment was a protective factor of OS and PFS. Grade 3 or 4 hypertension occurred in 14.3% of patients in the TACE-TKIs-C group and other high-grade toxic effects were infrequent. Conclusion: In patients with advanced HCC, TACE-TKIs-C may improve overall and progression-free survival outcomes over TACE-TKIs with manageable safety profile.

Association between sarcopenia and clinical outcomes in patients with hepatocellular carcinoma: an updated meta-analysis.

Although numerous studies have reported the association between sarcopenia and the prognosis of hepatocellular carcinoma (HCC) patients, there is lack of a newer and more comprehensive meta-analysis. Herein, a comprehensive literature search was performed on PubMed, Web of Science, the Cochrane Library, and Embase databases to identify relevant studies published up to February 2022. The outcomes were overall survival (OS), recurrence, progression-free survival, tumor response, severe postoperative complications, and toxicity of drugs. A total of 57 studies involving 9790 HCC patients were included in the meta-analysis. The pooled prevalence of sarcopenia in HCC patients was 41.7% (95% CI 36.2-47.2%). Results demonstrated that sarcopenia was significantly associated with impaired OS (HR: 1.93, 95% CI 1.73-2.17, P < 0.001), higher risk of tumor recurrence (HR: 1.75, 95% CI 1.56-1.96, P < 0.001), lower objective response rate (OR: 0.37 95% CI 0.17-0.81, P = 0.012), and more drug-related adverse events (OR: 2.23, 95% CI 1.17-4.28, P = 0.015) in HCC patients. The subgroup analyses revealed that the OS of patients at the early stage of tumor was more severely affected by sarcopenia than for patients at other stages. Moreover, the presence of cirrhosis and Child Pugh class B increased the hazard of mortality from sarcopenia. This study has shown that sarcopenia is highly associated with poor prognosis in HCC patients. In addition, cirrhosis and poor liver functional reserve increase the danger of sarcopenia. OS was more impaired in HCC patients with sarcopenia at early stage of tumor than at other tumor stages.

Evaluation of Transarterial Chemoembolization Protocol with Drug-Eluting Beads in Combination with Lipiodol for Hepatocellular Carcinoma: A Single-Center Controlled Study.

Objectives: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) and lipiodol (DEB-Lipiodol TACE) in the treatment of unresectable hepatocellular carcinoma (HCC) patients. Materials and Methods: The medical records of consecutive unresectable HCC patients who underwent DEB-TACE or DEB-Lipiodol TACE from June 2016 to July 2021 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared among the groups. Results: Three hundred and twenty-seven patients were enrolled in the study, including 293 patients in the DEB-TACE group and 34 patients in the DEB-Lipiodol TACE group. The objective response rate in the DEB-Lipiodol TACE group was 17.6%, significantly higher than that in the DEB-TACE group (5.8%, P=0.011). Similarly, DEB-Lipiodol TACE group also had a higher disease control rate (91.2% vs 68.6%, P=0.006). Median OS was 13 months (95% CI: 11.0 months and 15.0 months) and 22 months (95% CI: 17.3 months and 26.7 months) in the DEB-TACE group and DEB-Lipiodol TACE group, respectively (P=0.041). Meanwhile, median PFS was 7 months (95% CI: 5.2 months and 8.8 months) in the DEB-TACE group and 12 months (95% CI: 7.9 months and 16.1 months) in the DEB-Lipiodol TACE group (P=0.174). There was no statistically significant difference in AEs incidence among the two groups (P > 0.05). Conclusions: DEB-Lipiodol TACE was safe, well tolerated, and had a better efficacy compared with DEB-TACE in unresectable HCC patients.

Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study.

Objectives: To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. Results: There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2-25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable. Conclusion: TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.