A review of robot-assisted ultrasound examination: Systems and technology.

BACKGROUND: At present, the number and overall level of ultrasound (US) doctors cannot meet the medical needs, and the medical ultrasound robots will largely solve the shortage of medical resources. METHODS: According to the degree of automation, the handheld, semi-automatic and automatic ultrasound examination robot systems are summarised. Ultrasound scanning path planning and robot control are the keys to ensure that the robot systems can obtain high-quality images. Therefore, the ultrasound scanning path planning and control methods are summarised. The research progress and future trends are discussed. RESULTS: A variety of ultrasound robot systems have been applied to various medical works. With the continuous improvement of automation, the systems provide high-quality ultrasound images and image guidance for clinicians. CONCLUSION: Although the development of medical ultrasound robot still faces challenges, with the continuous progress of robot technology and communication technology, medical ultrasound robot will have great development potential and broad application space.

Blocking lncRNA HCG18 re-sensitizes Taxol resistant lung cancer cells to Taxol through modulating the miR-34a-5p/HDAC1 axis.

Lung cancer is one of the most frequently diagnosed cancers worldwide, associated with a poor survival rate. Taxol (Paclitaxel) is commonly used as a chemotherapeutic treatment for advanced lung cancers. While Taxol has improved clinical outcomes for lung cancer patients, a significant number of them develop resistance to Taxol, resulting in treatment failure. The role of the long noncoding RNA HCG18 in lung cancer and Taxol resistance has not yet been fully understood. To investigate this, we examined the expression of HCG18 and miR-34a-5p in lung tumors and normal lung tissues using qRT-PCR. We also assessed Taxol resistance through cell viability and apoptosis assays. Through the starBase online service, we analyzed the interactions between lncRNA and mRNA as well as miRNA and mRNA. We further validated the association between lncRNA and miRNA through luciferase and RNA pull-down assays. Our findings demonstrated that HCG18 was significantly upregulated in lung cancer tissues compared to normal lung tissues. Silencing HCG18 increased the sensitivity of lung cancer cells to Taxol. Additionally, our study established a Taxol-resistant cell line and observed a substantial upregulation of HCG18 in Taxol-resistant lung cancer cells. Bioinformatic analysis predicted that HCG18 could bind to miR-34a-5p, forming a competing endogenous RNA network, which was confirmed through luciferase assay. We found that miR-34a-5p was downregulated in lung cancer tissues and negatively correlated with Taxol resistance, as it directly bound to the 3'UTR region of HDAC1. Further results showed that inhibition of HCG18 significantly increased miR-34a-5p expression and sensitized lung cancer cells to Taxol. This sensitization could be reversed by inhibiting miR-34a-5p. Finally, we demonstrated in a xenograft mouse model that inhibition of HCG18 sensitized Taxol-resistant lung cancer cells to Taxol treatment by modulating the miR-34a-5p-HDAC1 axis. In conclusion, our in vitro and in vivo results uncover a novel molecular mechanism by which HCG18 promotes Taxol resistance through modulation of the miR-34a-5p/HDAC1 axis. These findings contribute to the diagnosis and treatment of chemo-resistant lung cancer.

NCF4 regulates antigen presentation of cysteine peptides by intracellular oxidative response and restricts activation of autoreactive and arthritogenic T cells.

Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematous, are regulated by polymorphisms in genes contributing to the NOX2 complex. Mutations in both Ncf1 and Ncf4 affect development of arthritis in experimental models of RA, but the different regulatory pathways mediated by NOX2-derived reactive oxygen species (ROS) have not yet been clarified. Here we address the possibility that intracellular ROS, regulated by the NCF4 protein (earlier often denoted p40phox) which interacts with endosomal membranes, could play an important role in the oxidation of cysteine peptides in mononuclear phagocytic cells, thereby regulating antigen presentation and activation of arthritogenic T cells. To study the role of NCF4 we used mice with an amino acid replacing mutation (NCF4R58A), which is known to affect interaction with endosomal membranes, leading to decreased intracellular ROS production. To study the impact of NCF4 on T cell activation, we used the glucose phosphate isomerase peptide GPI325-339, which contains two cysteine residues (325-339c-c). Macrophages from mice with the NCF458A mutation efficiently presented the peptide when the two cysteines were intact and not crosslinked, leading to a strong arthritogenic T cell response. T cell priming occurred in the draining lymph nodes (LNs) within 8 days after immunization. Clodronate treatment, which depletes antigen-presenting mononuclear phagocytes, ameliorated arthritis severity, whereas treatment with FYT720, which traps activated T cells in LNs, prohibited arthritis. We conclude that NCF4-dependent intracellular ROS maintains cysteine peptides in an oxidized crosslinked state, which prevents presentation of peptides recognized by non-tolerized T cells and thereby protects against autoimmune arthritis.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

Association between serum multi-protein biomarker profile and real-world disability in multiple sclerosis.

Few studies examined blood biomarkers informative of patient-reported outcome (PRO) of disability in people with multiple sclerosis (MS). We examined the associations between serum multi-protein biomarker profiles and patient-reported MS disability. In this cross-sectional study (2017-2020), adults with diagnosis of MS (or precursors) from two independent clinic-based cohorts were divided into a training and test set. For predictors, we examined seven clinical factors (age at sample collection, sex, race/ethnicity, disease subtype, disease duration, disease-modifying therapy [DMT], and time interval between sample collection and closest PRO assessment) and 19 serum protein biomarkers potentially associated with MS disease activity endpoints identified from prior studies. We trained machine learning (ML) models (Least Absolute Shrinkage and Selection Operator regression [LASSO], Random Forest, Extreme Gradient Boosting, Support Vector Machines, stacking ensemble learning, and stacking classification) for predicting Patient Determined Disease Steps (PDDS) score as the primary endpoint and reported model performance using the held-out test set. The study included 431 participants (mean age 49 years, 81% women, 94% non-Hispanic White). For binary PDDS score, combined feature input of routine clinical factors and the 19 proteins consistently outperformed base models (comprising clinical features alone or clinical features plus one single protein at a time) in predicting severe (PDDS ≥ 4) versus mild/moderate (PDDS < 4) disability across multiple machine learning approaches, with LASSO achieving the best area under the curve (AUCPDDS = 0.91) and other metrics. For ordinal PDDS score, LASSO model comprising combined clinical factors and 19 proteins as feature input (R2PDDS = 0.31) again outperformed base models. The two best-performing LASSO models (i.e., binary and ordinal PDDS score) shared six clinical features (age, sex, race/ethnicity, disease subtype, disease duration, DMT efficacy) and nine proteins (cluster of differentiation 6, CUB-domain-containing protein 1, contactin-2, interleukin-12 subunit-beta, neurofilament light chain [NfL], protogenin, serpin family A member 9, tumor necrosis factor superfamily member 13B, versican). By comparison, LASSO models with clinical features plus one single protein at a time as feature input did not select either NfL or glial fibrillary acidic protein (GFAP) as a final feature. Forcing either NfL or GFAP as a single protein feature into models did not improve performance beyond clinical features alone. Stacking classification model using five functional pathways to represent multiple proteins as meta-features implicated those involved in neuroaxonal integrity as significant contributors to predictive performance. Thus, serum multi-protein biomarker profiles improve the prediction of real-world MS disability status beyond clinical profile alone or clinical profile plus single protein biomarker, reaching clinically actionable performance.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Identification of aneuploidy-related gene signature to predict survival in head and neck squamous cell carcinomas.

BACKGROUND: To parse the characteristics of aneuploidy related riskscore (ARS) model in head and neck squamous cell carcinomas (HNSC) and their predictive ability on patient prognosis. METHODS: Molecular subtyping of HNSC specimens was clustered by Copy Number Variation (CNV) data from The Cancer Genome Atlas (TCGA) dataset applying consistent clustering, followed by immune condition evaluation, differentially expressed genes (DEGs) analysis and DEGs function annotation. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction, Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analysis were implemented to construct an ARS model. A nomogram for clinic practice was designed by rms package. Immunotherapy evaluation and drug sensitivity prediction were also carried out. RESULTS: We stratified HNSC patients into three different molecular subgroups, with the best prognosis in C1 cluster among 3 clusters. C1 cluster displayed greatest immune infiltration status. The most DEGs between C1 and C2 groups, mainly enriched in cell cycle and immune function. We constructed a nine-gene ARS model (ICOS, IL21R, CCR7, SELL, CYTIP, ZAP70, CCR4, S1PR4 and CD79A) that effectively differentiates between high- and low-risk patients. Patients in low ARS group showed a higher sensitivity to immunotherapy. A nomogram built by integrating ARS and clinic-pathological characteristics helped predict clinic survival benefit. Drug sensitivity evaluation found that 4/9 inhibitor drugs (MK-8776, AZD5438, PD-0332991, PHA-665752) acted on the cell cycle. CONCLUSIONS: We classified 3 molecular subtypes for HNSC patients and established an ARS prognostic model, which offered a prospective direction for prognosis in HNSC.

Iodine-125 seed implantation in the treatment of malignant tumors.

Malignant tumors are major causes of morbidity and mortality in China. Despite advances in surgical, radiological, chemotherapeutic, molecular targeting, and immunotherapeutic treatments, patients with malignant tumors still have poor prognoses. Low-dose-rate brachytherapy, specifically 125I seed implantation, is beneficial because of its high local delivery dose and minimal damage to surrounding tissues. Consequently, it has gained increasing acceptance as a treatment modality for various malignant tumors. In this study, we explored the fundamental principles, clinical applications, and new technologies associated with 125I radioactive seed implantation.

Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Effects of cellulose nanofibrils treatment on antioxidant properties and aroma of fresh-cut apples.

Horticultural products tend to deteriorate during postharvest storage and processing. In this study, cellulose nanofibers (CNFs) were prepared from wood to investigate the effects of CNF treatment on the storage quality, aroma composition, and antioxidant system of fresh-cut apple (Malus domestica) wedges. Compared with control treatment, CNF coating treatment significantly improved the appearance of apple wedges; reduced the decay rate of apple wedges; and delayed the decline in weight loss, firmness, and titratable acid during storage. Gas chromatography-mass spectrometry showed that CNF treatment could maintain the aroma components of apple wedges (stored for 4 days). Further investigations showed that CNF treatment increased the antioxidant system level and decreased reactive oxygen species content and membrane lipid peroxidation level of apple wedges. Overall, this study showed that CNF coating could effectively maintain the quality of fresh-cut apples during cold storage.

Mutational and Transcriptional Characterization Establishes Prognostic Models for Resectable Lung Squamous Cell Carcinoma.

Background: The prognosis of non-small cell lung cancer (NSCLC) patients has been comprehensively studied. However, the prognosis of resectable (stage I-IIIA) lung squamous cell carcinoma (LUSC) has not been thoroughly investigated at genomic and transcriptional levels. Methods: Data of genomic alterations and transcriptional-level changes of 355 stage I-IIIA LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database, together with the clinicopathological information (training cohort). A validation cohort of 91 patients was retrospectively recruited. Data were analyzed and figures were plotted using the R software. Results: Training cohort was established with 355 patients. TP53 (78%), TTN (68%), CSMD3 (39%), MUT16 (36%) and RYR2 (36%) were genes with the highest mutational frequency. BRINP3, COL11A1, GRIN2B, MUC5B, NLRP3 and TENM3 exhibited significant higher mutational frequency in stage III (P < 0.05). Patients with stage III also exhibited significantly higher tumor mutational burden (TMB) than those with stage I (P < 0.01). The mutational status of 10 genes were found to have significant stratification on patient prognosis. TMB at threshold of 25 percentile (TMB = 2.39 muts/Mb) also significantly stratified the patient prognosis (P = 0.0003). Univariate and multivariate analyses revealed TTN, ADGRB3, MYH7 and MYH15 mutational status and TMB as independent risk factors. Further analysis of transcriptional profile revealed many significantly up- and down-regulated genes, and multivariate analysis found the transcriptional levels of seven genes as independent risk factors. Significant factors from the multivariate analyses were used to establish a Nomogram model to quantify the risk in prognosis of individual LUSC patients. The model was validated with a cohort containing 91 patients, which showed good predicting efficacy and consistency. Conclusion: The influencing factors of prognosis of stage I-III LUSC patients have been revealed. Risk factors including gender, T stage, cancer location, and the mutational and transcriptional status of several genes were used to establish a Nomogram model to assess the patient prognosis. Subsequent validation proved its effectiveness.

LncRNA WDR11-AS1 Promotes Extracellular Matrix Synthesis in Osteoarthritis by Directly Interacting with RNA-Binding Protein PABPC1 to Stabilize SOX9 Expression.

Osteoarthritis (OA) is a degenerative disease of articular cartilage that is mainly characterized by chronic and mild inflammation of the joints. Recently, many studies have reported the crucial roles of long noncoding RNAs (lncRNAs) in OA as gene transcriptional regulatory factors, diagnostic biomarkers, or therapeutic targets. However, the exact mechanisms of lncRNAs in the regulation of OA progression remain unclear. In the present study, the lncRNA WDR11 divergent transcript (lncRNA WDR11-AS1) was shown to be downregulated in osteoarthritic cartilage tissues from patients, and to promote extracellular matrix (ECM) synthesis in osteoarthritic chondrocytes with knockdown and overexpression experiments. This function of lncRNA WDR11-AS1 was linked to its ability to interact with the polyadenylate-binding protein cytoplasmic 1 (PABPC1), which was screened by RNA pulldown and mass spectrometry analyses. PABPC1 was discovered to bind ECM-related mRNAs such as SOX9, and the inhibition of PABPC1 improved the mRNA stability of SOX9 to mitigate OA progression. Our results suggest that lncRNA WDR11-AS1 has a promising inhibitory effect on inflammation-induced ECM degradation in OA by directly binding PABPC1, thereby establishing lncRNA WDR11-AS1 and PABPC1 as potential therapeutic targets in the treatment of OA.

SLC38A6 expression in macrophages exacerbates pulmonary inflammation.

Pulmonary inflammation involves complex changes of the immune cells, in which macrophages play important roles and their function might be influenced by metabolism. Slc38a6 acts as a carrier of nutrient for macrophages (Mφ) to exert the function. In this study, pneumonia patient blood was found up-regulated SLC38A6 expression, which correlated with monocytes number and white blood cell number. The similar result was also shown in LPS induced sepsis mice. To reveal the key role of Slc38a6, we used systemic and conditional knock-out mice. Either systemic or LyzCRE specific knock-out could alleviate the severity of sepsis mice, reduce the proinflammatory cytokine TNF-α and IL-1ß expression in serum and decrease the monocytes number in bronchial alveolar lavage and peritoneal lavage via flow cytometry. In order to reveal the signal of up-regulated Slc38a6, the Tlr4 signal inhibitor TAK242 and TLR4 knock-out mice were used. By blocking Tlr4 signal in macrophages via TAK242, the expression of Slc38a6 was down-regulated synchronously, and the same results were also found in Tlr4 knock-out macrophages. However, in the overexpressed Slc38a6 macrophages, blocking Tlr4 signal via TAK242, 20% of the mRNA expression of IL-1ß still could be expressed, indicating that up-regulated Slc38a6 participates in IL-1ß expression process. Collectively, it is the first time showed that an amino acid transporter SLC38A6 up-regulated in monocytes/macrophages promotes activation in pulmonary inflammation. SLC38A6 might be a promising target molecule for pulmonary inflammation treatment.

Percutaneous ablation of liver metastases from colorectal cancer: a comparison between the outcomes of ultrasound guidance and CT guidance using propensity score matching.

PURPOSE: The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM). METHODS: This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients' initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)-free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups. RESULTS: PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040). CONCLUSION: For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.

Soil Conditioner Affects Tobacco Rhizosphere Soil Microecology.

Reasonable fertilization management can increase nutrient content and enzyme activity in rhizosphere soil, and even increase soil microbial richness. However, different fertilizers could raise distinct influences on the soil properties, including soil environmental factors (physicochemical properties and enzymatic activities) and microbial community. Here, the effects of two soil amendments (microbial fertilizer and woody peat) on environmental factors and microbial community structure in tobacco rhizosphere soil were evaluated, with the correlations between microbes and environmental factors explored. As the results, microbial fertilizer could effectively alleviate soil acidification, increase available potassium and organic matter contents in soil, and was also beneficial to increase nitrate reductase activity in rhizosphere soil. Fertilizers cause changes in the abundance of certain microbes in the soil. Besides, it was shown that the candidate phyla Gal15, Acidobacterota, Latescibacterota, Mortierellommycota, Basidiomycota, and Rozellomycota in tobacco rhizosphere soil had significant correlation with soil environmental factors. Through the functional analysis of these populations, it can be deduced that the changes in the abundance of certain microorganisms may be an important reason for the differences in environmental factors. All these indicated that the differences of environmental factors in different treatments are closely related to the abundance of some special soil microorganisms. Studying the life activities of these microbes would provide good guidance for exploring the interaction among crops, soil, and microorganisms and improving crop yields.

Retrograde venous coil embolization prior to transarterial chemoembolization in hepatocellular carcinoma with arterio-hepatic venous shunts.

PURPOSE This study explored the clinical efficacy of transcatheter retrograde shunt occlusion with coils to prevent pulmonary oil or particle embolization prior to transarterial chemoembolization (TACE) in patients with artero-hepatic venous shunts (AHVS) secondary to hepatocellular carcinoma (HCC). METHODS From July 2017 to January 2021, 6 patients with advanced, unresectable HCC were found to have an AHVS by hepatic arteriography at the time of attempted TACE. The AHVS was embolized ret rogradely with metal coils through a transfemoral or transjugular venous approach. After venous embolization and confirmation of the absence of the AHVS, TACE was performed using an emul sion of iodized oil and doxorubicin or drug-eluting beads. Follow-up computed tomography (CT) was performed within 1 month after the first TACE to evaluate the results and complications. RESULTS Hepatic angiography after venous embolization showed that AHVS had utterly disappeared in all patients during the operation. The immediate technical success of the retrograde venous embo lization was 100%. The AHVS had disappeared entirely during the follow-up period through triple-phase enhancement CT scanning. According to the modified response evaluation criteria in solid tumors, TACE in all 6 patients had a disease control response rate of 100% (6/6) with complete response in 2 patients and partial response in 4 patients. One patient died during the 6-month follow-up, and the other 5 were still alive. No complications related to pulmonary embolism occurred. CONCLUSION Retrograde venous coil embolization of AHVS via the draining hepatic vein appears to be a safe, feasible, and effective treatment to allow TACE treatment without pulmonary embolic events. This approach appears to provide better tumor control and effectively decreases the occurrence of pulmonary embolism.

Clinical efficacy of CT-guided 125I brachytherapy in patients with local residual or recurrent hepatocellular carcinoma after thermal ablation.

OBJECTIVES: Treatment methods of local residual or recurrent hepatocellular carcinoma (HCC) after thermal ablation are limited. Therefore, our study aimed to explore the efficacy and prognostic factors of 125I brachytherapy for local residual or recurrent lesion after thermal ablation. METHODS: A total of 114 patients with 212 local residual or recurrent HCC tumors after thermal ablation underwent 125I brachytherapy. Local progression-free survival (LPFS) and prognostic factors were analyzed by Kaplan-Meier curves and the Cox model. RESULTS: After a 6-month follow-up, the percentage of patients who achieved complete response (CR), partial response (PR), and stable disease (SD) was 57%, 13.2%, and 5.2%, respectively. The 1-, 2-, and 3-year LPFS rates were 58.7%, 50.0%, and 41.2%, respectively. Portal vein tumor thrombus (PVTT) (p = 0.03), the number of intrahepatic tumors (p = 0.01), and AFP level (p = 0.02) were independent risk factors for local tumor progression (LTP). The median LPFS in patients without PVTT (22 months) was much longer compared to those with PVTT (10 months). The median LPFS in patients with less than three intrahepatic lesions improved from 17 to 24 months. The median LPFS was only 5 months in the high AFP group, but was prolonged with a decrease in AFP level (24 months). No severe complications were recorded. All complications were controllable and treatable. CONCLUSIONS: CT-guided 125I brachytherapy was a safe and effective treatment for patients with local residual or recurrent HCC after thermal ablation to improve local control rate.

TGF-ß1 contributes to the hepatic inflammation in animal models with nonalcoholic steatohepatitis by Smad3/TLR2 signaling pathway.

Non-alcoholic fatty liver disease (NAFLD) is increasingly affecting human health and the economy worldwide due to various factors. Here, we found that the expression of TGF-ß1 and TLR2 was significantly up-regulated in liver samples from both rats and mice nonalcoholic steatohepatitis (NASH) models. By constructing corresponding cell model, we found that TGF-ß1 challenge can positively regulate the expression of TLR2 and p-Smad2/3, and the dual luciferase reporter gene system and EMSA assay confirmed the existence of Smad3 binding site (-916 ∼ -906) in the promoter region of TLR2. The overexpression and interference changes of Smad2/3 further verified the above experimental results. Taken together, these findings suggest that TGF-ß1 promotes TLR2 transcription and its target gene expression via Smad3, leading to malignant exacerbation of liver inflammation in NASH, which provides new insights into the treatment of NASH.