A Fully Methylated Cyclic Ether Solvent Enables Graphite Anode Cycling at Low Temperatures.

Graphite anode suffers from great capacity loss and larger cell polarization under low-temperature conditions in lithium-ion batteries (LIBs), which are mainly caused by the high energy barrier for the Li+ desolvation process and sluggish Li+ transfer rate across the solid electrolyte interface (SEI). Regulating an electrolyte with an anion-dominated solvation structure could synchronously stabilize the interface and boost the reaction kinetics of the graphite anode. Herein, a highly ionic conductive electrolyte consisting of a fully methylated cyclic ether solvent of 2,2,4,4,5,5-hexamethyl-1,3-dioxolane (HMD) and fluoroethylene carbonate (FEC) cosolvent was designed. The high electron-donating effect and steric hindrance of -(CH3)2 in HMD endow the HMD-based electrolyte with high ionic conductivity but lower coordination numbers with Li+, and an anion-dominated solvation structure was formed. Such configuration can accelerate the desolvation process and induce the forming of a LiF-rich SEI film on the anode, avoiding the solvent coembedding into graphite and enhancing the ion migration rate under low temperatures. The assembled Li||graphite cell with the tame electrolyte outperformed the conventional carbonates-based cell, showing 93.8% capacity retention after 227 cycles for the DF-based cell compared to 64.7% after 150 cycles. It also exhibited a prolonged cycle life for 200 rounds with 81% capacity retention under -20 °C. Therefore, this work offers a valuable thought for solvent design and provides approaches to electrolyte design for low-temperature LIBs.

Electrolyte Regulation in Stabilizing the Interface of a Cobalt-Free Layered Cathode for 4.8 V High-Voltage Lithium-Ion Batteries.

The cobalt-free layered oxide cathode of LiNi0.65Mn0.35O2 is promising for high-energy-density lithium-ion batteries (LIBs). However, under high-voltage conditions, severe side reactions between the Co-free cathode and electrolyte, as well as grain boundary cracks and pulverization of particles, hinder its practical applications. Herein, an electrolyte regulation strategy is proposed by adding fluoroethylene carbonate (FEC) and LiPO2F2 as electrolyte additives in carbonate-based electrolytes to address the above issues. As a result, a homogeneous and dense organic-inorganic hybrid cathode electrolyte interface (CEI) film is formed on the cathode surface. The CEI film consists of C-F, LiF, Li2CO3, and LixPOyFz species, which is proven to be highly conductive and effective in suppressing structure damage and alleviating the interfacial reactions between the cathode and electrolyte. With such a CEI film, the interfacial stability of the Co-free cathode and the high-voltage cycling performance of Li||LiNi0.65Mn0.35O2 are greatly improved. A reversible capacity of 155.1 mAh g-1 and a capacity retention of 81.3% over 150 cycles are attained at a 4.8 V charge cutoff voltage with the tamed electrolyte, whereas the cell without the additives only retains 76.1% capacity retention. Therefore, our work demonstrates the synergistic effect of FEC and LiPO2F2 in stabilizing the interface of Co-free cathode materials and provides an alternative strategy for the electrolyte design of high-voltage LIBs.

Chemotherapy alone versus chemotherapy plus 125I brachytherapy for the second-line treatment of locally recurrent cervical cancer after/with radical treatment: A propensity score analysis.

Rationale and objectives: The primary aim of this study was to conduct a retrospective comparative analysis of the survival outcomes in patients with recurrent cervical cancer (CC). Specifically, we aimed to compare the efficacy of chemotherapy alone versus the combined approach of chemotherapy and 125I brachytherapy subsequent to the failure of initial chemotherapy treatment. Materials and methods: Patients diagnosed with recurrent CC subsequent to the failure of initial chemotherapy from January 2007 to December 2016 were enrolled from 2 hospitals. These patients were then divided into two groups: Group A, which underwent second-line chemotherapy alone, and Group B, which received both second-line chemotherapy and 125I brachytherapy. The assessment of overall survival (OS) and progression-free survival (PFS) was carried out through propensity score matching (PSM) (1:1), Kaplan-Meier curves, log-rank tests, and Cox proportional hazard regression for survival analysis. Results: A matched cohort comprising 88 patients each in Group A and Group B was included in the study. In Group A, the 1-, 2-, and 3-year cumulative PFS rates were 40.9 %, 15.9 %, and 5.7 % respectively, while in Group B, these rates were significantly higher at 79.5 %, 48.9 %, and 25.0 % (P = 0.003). Similarly, the 1-, 2-, and 3-year cumulative OS rates among Group A were 67.0 %, 27.3 %, and 5.7 % compared to 89.8 %, 63.6 %, and 30.7 % among Group B, suggesting a difference with statistical significance (P < 0.001) between the two groups. Moreover, the incidence of complications was similar between groups (P = 0.698). Conclusions: Our findings suggest that the combined approach of chemotherapy and 125I brachytherapy yields superior therapeutic effects but similar complication rates compared to chemotherapy alone in patients experiencing local recurrence of CC following failed initial chemotherapy.

Transarterial Chemoembolization Combined with Lenvatinib Plus Sequential Microwave Ablation for Large Hepatocellular Carcinoma Beyond Up-to-Seven Criteria: A Retrospective Cohort Study.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the efficacy and safety of transarterial chemoembolization (TACE) combined with Lenvatinib plus sequential microwave ablation (MWA) for the treatment of patients with large hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS: This retrospective cohort study assessed the medical records of patients with large HCC who underwent TACE combined with Lenvatinib plus sequential MWA (TLM) or TACE plus sequential MWA (TM). Lenvatinib was administered to patients within 3-5 days after TACE and sequential MWA was performed once they met the criteria for curative ablation after TACE or the combination therapy. The progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared between two groups. RESULTS: Of the 81 patients who underwent TLM or TM, 64 who met the eligibility criteria were included in this study. Among them, 28 patients underwent TLM and 36 underwent TM. The inverse probability weighting method (IPTW) was used to balance differences between two groups. The TLM group had longer PFS than the TM group (median, before IPTW: 18.53 vs. 5.62 months, p < 0.001; median, after IPTW: 28.27 vs. 5.30 months, p < 0.001). Univariate and multivariate analyses revealed that TLM and the maximum tumor diameter were independent prognostic factors for PFS. The overall incidence rate of minor complications related to TACE or MWA was lower in the TLM group (32.1% vs. 66.7%, p = 0.006). CONCLUSION: TACE combined with Lenvatinib plus sequential MWA can prolong the progression-free survival of patients with large HCC beyond up-to-seven criteria.

Dual Spatially Localized DNA Walker for Fast and Efficient RNA Detection.

DNA walkers, which are synthetic nanodevices that drive the processive movement of nucleic acids along a well-designed track, have emerged as a powerful tool in biosynthesis, biocomputing, and biosensing due to their exquisite programmability, good biocompatibility, and efficient signal amplification capacity. However, many existing approaches are still hindered by limited reaction kinetics. Herein, we designed a dual spatially localized DNA walker that utilized bipedal catalysts to drive high-speed stochastic movement along three-dimensional tracks via a proximity-driven catalytic hairpin assembly. We demonstrated that the dual colocalization of autocatalytic circuits significantly increased their local concentrations and accelerated reaction kinetics through proximity. We also showed that the use of bipedal catalysts further improved reaction rates compared with unipedal catalysts. Taking advantage of these unique features, we constructed an RNA-responsive PCHA walker for mRNA imaging in live cells, providing a novel and efficient tool for biomolecule detection and biological functions regulation.

Genetically encodable tagging and sensing systems for fluorescent RNA imaging.

Live cell imaging of RNAs is crucial to interrogate their fundamental roles in various biological processes. The highly spatiotemporal dynamic nature of RNA abundance and localization has presented great challenges for RNA imaging. Genetically encodable tagging and sensing (GETS) systems that can be continuously produced in living systems have afforded promising tools for imaging and sensing RNA dynamics in live cells. Here we review the recent advances of GETS systems that have been developed for RNA tagging and sensing in live cells. We first describe the various GETS systems using MS2-bacteriophage-MS2 coat protein, pumilio homology domain and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9/13 for RNA labeling and tracking. The progresses of GETS systems for fluorogenic labeling and/or sensing RNAs by engineering light-up RNA aptamers, CRISPR-Cas9 systems and RNA aptamer stabilized fluorogenic proteins are then elaborated. The challenges and future perspectives in this field are finally discussed. With the continuing development, GETS systems will afford powerful tools to elucidate RNA biology in living systems.

1,3-Dimethyl-2-imidazolidinone: an ideal electrolyte solvent for high-performance Li-O2 battery with pretreated Li anode.

Electrolytes are widely considered as a key component in Li-O2 batteries (LOBs) because they greatly affect the discharge-charge reaction kinetics and reversibility. Herein, we report that 1,3-dimethyl-2-imidazolidinone (DMI) is an excellent electrolyte solvent for LOBs. Comparing with conventional ether and sulfone based electrolytes, it has higher Li2O2 and Li2CO3 solubility, which on the one hand depresses cathode passivation during discharge, and on the other hand promotes the liquid-phase redox shuttling during charge, and consequently lowers the overpotential and improves the cyclability of the battery. However, despite the many advantages at the cathode side, DMI is not stable with bare Li anode. Thus, we have developed a pretreatment method to grow a protective artificial solid-state electrolyte interface (SEI) to prevent the unfavorable side-reactions on Li. The SEI film was formed via the reaction between fluorine-rich organic reagents and Li metal. It is composed of highly Li+-conducting LixBOy, LiF, LixNOy, Li3N particles and some organic compounds, in which LixBOy serves as a binder to enhance its mechanical strength. With the protective SEI, the coulombic efficiency of Li plating/stripping in DMI electrolyte increased from 20% to 98.5% and the fixed capacity cycle life of the assembled LOB was elongated to 205 rounds, which was almost fivefold of the cycle life in dimethyl sulfoxide (DMSO) or tetraglyme (TEGDME) based electrolytes. Our work demonstrates that molecular polarity and ionic solvation structure are the primary issues to be considered when designing high performance Li-O2 battery electrolytes, and cross-linked artificial SEI is effective in improving the anodic stability.

Temporal-spatial change of China's coastal ecosystems health and driving factors analysis.

Understanding the spatial distribution pattern change and driving factors behind ecosystem health is essential to ecosystem management and restoration. However, in the research of regional ecosystem health, there is little research on ecosystem health in coastal regions, and there is little exploration of its temporal and spatial pattern change and its driving factors. In this study, we use the Vigor-Organization-Resilience-Services (VORS) model and marine ecosystem health index to diagnose the ecosystem health of the whole coastal area of China over the last 20 years, and find the main contributing factors affecting ecosystem health with the help of geographic detectors and geographic weighted regression analysis. Our results show that: (1) the ecosystem health level in the south of the coastal region is higher than that in the north, mainly with 30° north latitude as the main dividing line. (2) The regions with high change rate are mainly concentrated in Bohai Bay, the Yangtze River Estuary, Hangzhou Bay and the Pearl River Estuary, and the change is mainly negative. (3) Both natural and human factors have an impact on ecosystem health, and the influencing factors are different on different scales. The interaction between different factors is greater than the impact of a single factor on ecosystem health. The study puts forward a new evaluation framework for the study of ecosystem health in coastal areas, which can be applied to other coastal areas with similar conditions, and can help the sustainable and healthy development of coastal areas.

Prognostic role of multiparameter MRI and radiomics in progression of advanced unresectable hepatocellular carcinoma following combined transcatheter arterial chemoembolization and lenvatinib therapy.

BACKGROUND: Current study aims to determine the prognostic value of Multiparameter MRI after combined Lenvatinib and TACE therapy in patients with advanced unresectable hepatocellular carcinoma (HCC). METHODS: A total of 61 HCC patients with pre-treatment Multiparameter MRI in Sun Yat-sen University Cancer Center from January 2019 to March 2021 were recruited in the current study. All patients received combined Lenvatinib and TACE treatment. Potential clinical and imaging risk factors for disease progression were analyzed using Cox regression model. Each patient extracts signs from the following 7 sequences: T1WI, T1WI arterial phase, T1WI portal phase, T1WI delay phase, T2WI, DWI (b = 800), ADC.1782 quantitative 3D radiomic features were extracted for each sequence, A random forest algorithm is used to select the first 20 features by feature importance. 7 logit regression-based prediction model was built for seven sequences based on the selected features and fivefold cross validation was used to evaluate the performance of each model. RESULTS: CR, PR, SD were reported in 14 (23.0%), 35 (57.4%) and 7 (11.5%) patients, respectively. In multivariate analysis, tumor number (hazard ratio, HR = 4.64, 95% CI 1.03-20.88), and arterial phase intensity enhancement (HR = 0.24, 95% CI 0.09-0.64; P = 0.004) emerged as independent risk factors for disease progression. In addition to clinical factors, the radiomics signature enhanced the accuracy of the clinical model in predicting disease progression, with an AUC of 0.71, a sensitivity of 0.99%, and a specificity of 0.95. CONCLUSION: Radiomic signatures derived from pretreatment MRIs could predict response to combined Lenvatinib and TACE therapy. Furthermore, it can increase the accuracy of a combined model for predicting disease progression. In order to improve clinical outcomes, clinicians may use this to select an optimal treatment strategy and develop a personalized monitoring protocol.

Recent Advances on DNAzyme-Based Sensing.

Owing to the high sensitivity, excellent programmability, and flexible obtainment through in vitro selection, RNA-cleaving DNAzymes have attracted increasing interest in developing DNAzyme-based sensors. In this review, we summarize the recent advances on DNAzyme-based sensing applications. We initially conclude two general strategies to expand the library of DNAzmes, in vitro selection to discover new DNAzymes towards different targets of interest and chemical modifications to endue the existing DNAzymes with new function or properties. We then discuss the recent applications of DNAzyme-based sensors for the detection of a variety of important biomoleucles both in vitro and in vivo. Finally, perspectives on the challenges and future directions in the development of DNAzyme-based sensors are provided.

Ganglioside-monosialic acid (GM1) for prevention of chemotherapy-induced peripheral neuropathy: a meta-analysis with trial sequential analysis.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect that largely remains an unresolved clinical issue, leading to long-term morbidity. This meta-analysis aimed to evaluate the efficacy and safety of Ganglioside-monosialic acid (GM1) in preventing CIPN. METHODS: Systematic literature searches of PubMed, Web of Science, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were performed to identify randomized controlled trials and cohort studies that evaluated the efficacy of GM1 for preventing CIPN. Conventional meta-analysis with a random-effects model and trial sequential analysis (TSA) were performed. RESULTS: A total of five studies involving 868 participants were included. The results showed that GM1 did not reduce the overall incidence of grade ≥ 2 CIPN when the common terminology criteria for adverse events (CTCAE) was used (OR 0.34, 95% CI 0.34-1.11). Subgroup analyses showed that GM1 could not reduce the risk of CTCAE grade ≥ 2 CIPN (OR 0.63, 95% CI 0.35-1.13) and neurotoxicity criteria of Debiopharm (DEB-NTC) grade ≥ 2 CIPN (OR 0.25, 95% CI 0.01-7.10) in oxaliplatin-treated patients, despite that GM1 was associated with a reduced risk of CTCAE grade ≥ 2 CIPN in the taxane subgroup of one study (OR 0.003, 95% CI 0.00-0.05). These results were confirmed by the sub-analysis of randomized controlled trials (RCTs). In TSA, the z-curve for the taxane subgroup crossed the upper trial sequential monitoring boundary (TSMB) but do not reach the required information size (RIS). The z-curves for the oxaliplatin subgroup remained in the nonsignificant area and did not reach the RIS. Further, GM1 did not influence the rate of response to chemotherapy and CTCAE grade ≥ 2 adverse events such as fatigue, nausea, diarrhea, and rash. CONCLUSIONS: GM1 seemed to be well-tolerated and did not influence the anti-cancer effects of chemotherapeutic agents. Although the data did not confirm the effectiveness of GM1 in preventing oxaliplatin-induced peripheral neuropathy, GM1 might be able to prevent taxane-induced peripheral neuropathy. More studies are required in different ethnic populations receiving taxane-based chemotherapy to confirm these findings.

Four types of tumor progression after microwave ablation of single hepatocellular carcinoma of ≤5 cm: incidence, risk factors and clinical significance.

OBJECTIVES: To evaluate the incidence, risk factors and clinical significance of four types of tumor progression (TP) after microwave ablation (MWA) of single hepatocellular carcinoma (HCC) of <5 cm. METHODS: The data of 340 treatment-naïve, HCC patients with a single HCC of <5 cm underwent MWA between April 2012 and November 2017 were retrospectively reviewed. TPs including local tumor progression (LTP), intrahepatic distant recurrence (IDR), aggressive intrasegmental recurrence (AIR) and extrahepatic distant recurrence (EDR) were reviewed and compared between BCLC stage 0 and A. Univariate and multivariate analysis were performed on clinicopathological variables and different TPs to identify factors affecting long-term overall survival (OS). RESULTS: In a median follow-up period of 25.6 months (range, 3.1-61.4 months), the rate of LTP, IDR, AIR and EDR was 6.2% (21/340), 29.1% (98/340), 3.2% (11/340) and 7.9% (27/340). The four types of TP occurrence rates in BCLC stage 0 were comparable to those in BCLC stage A (p = 0.492, 0.971, 0.681 and 0.219). Univariate analysis showed that age (p < 0.001, hazard ratio [HR] = 2.783), comorbidities (p = 0.042, HR = 1.864), IDR, AIR and EDR (p = 0.027, HR = 1.719; p = 0.001, HR = 3.628; p = 0.009, HR = 2.638) were independently associated with OS. Multivariate analysis showed older age (p < 0.001, HR = 2.478), the occurrence of AIR (p < 0.001, HR = 2.648) and the occurrence of EDR (p = 0.002, HR = 2.222), were associated with poor OS. CONCLUSIONS: The occurrence rate of IDR is the highest of all TPs following MWA of a single HCC of <5cm. Old age, AIR and EDR had an adverse effect on long-term OS.

Consensus of Minimally Invasive and Multidisciplinary Comprehensive Treatment for Hepatocellular Carcinoma - 2020 Guangzhou Recommendations.

In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments [such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE)], and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.

"Repaired and Activated" DNAzyme Enables the Monitoring of DNA Alkylation Repair in Live Cells.

Direct measurement of DNA repair is critical for the annotation of their clinical relevance and the discovery of drugs for cancer therapy. Here we reported a "repaired and activated" DNAzyme (RADzyme) by incorporating a single methyl lesion (O6 MeG, 3MeC, or 1MeA) at designated positions through systematic screening. We found that the catalytic activity of the RADzyme was remarkably suppressed and could be restored via enzyme-mediated DNA repair. Benefit from these findings, a fluorogenic RADzyme sensor was developed for the monitoring of MGMT-mediated repair of O6 MeG lesion. Importantly, the sensor allowed the evaluation of MGMT repair activity in different cells and under drugs treatment. Furthermore, another RADzyme sensor was engineered for the monitoring of ALKBH2-mediated repair of 3MeC lesion. This strategy provides a simple and versatile tool for the study of the basic biology of DNA repair, clinical diagnosis and therapeutic assessment.

Radiofrequency versus microwave ablation for hepatocellular carcinoma within the Milan criteria in challenging locations: a retrospective controlled study.

PURPOSE: The aim of this study was to compare the safety and efficacy of radiofrequency ablation (RFA) with microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria in challenging locations. METHODS: This study retrospectively investigated 201 consecutive patients with Milan criteria HCCs who underwent RFA (RFA group, n = 150) or MWA (MWA group, n = 51) between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), local tumor control, and treatment-related complications were compared between the two groups. Prognostic factors were analyzed using the Cox proportional hazard regression model. RESULTS: Median follow-up duration was 36.7 months (range: 6.2-64.0 months). Cumulative 1-, 3-, and 5-year OS rates were 97.9%, 92.3%, and 80.6% in the MWA group and 96.4%, 87.4%, and 78.2% in the RFA group, respectively, (P = 0.450). Cumulative RFS rates at 1, 3, and 5 years were 93.2%, 74.4%, and 63.7% in the MWA group and 80.3%, 57.3%, and 49.6% in the RFA group, respectively, (P = 0.097). Multivariate analyses showed that variable categories "patient age above 65 years" (P = 0.004) and "more than one tumor" (P = 0.004) were associated with overall mortality, and "patient age above 65 years" (P = 0.048) and "tumor size greater than 3 cm" (P = 0.009) were associated with inferior RFS. The incidences of major complications were not significantly different between the two groups (3.3% vs 3.9%, P = 0.843). CONCLUSIONS: RFA and MWA were associated with comparable safety and efficacy for HCC within the Milan criteria in challenging locations. Further study in a large, multi-center patient cohort is necessary to validate the results.

Small single perivascular hepatocellular carcinoma: comparisons of radiofrequency ablation and microwave ablation by using propensity score analysis.

OBJECTIVES: We aimed to compare the therapeutic outcomes of radiofrequency ablation (RFA) and microwave ablation (MWA) as first-line therapies in patients with small single perivascular hepatocellular carcinoma (HCC). METHODS: A total of 144 eligible patients with small (≤ 3 cm) single perivascular (proximity to hepatic and portal veins) HCC who underwent RFA (N = 70) or MWA (N = 74) as first-line treatment were included. The overall survival (OS), disease-free survival (DFS), and local tumor progression (LTP) rates between the two ablation modalities were compared. The inverse probability of treatment weighting (IPTW) method was used to reduce selection bias. Subgroup analysis was performed according to the type of hepatic vessels. RESULTS: After a median follow-up time of 38.2 months, there were no significant differences in OS (5-year OS: RFA 77.7% vs. MWA 74.6%; p = 0.600) and DFS (5-year DFS: RFA 24.7% vs. MWA 40.4%; p = 0.570). However, a significantly higher LTP rate was observed in the RFA group than the MWA group (5-year LTP: RFA 24.3% vs. MWA 8.4%; p = 0.030). IPTW-adjusted analyses revealed similar results. The treatment modality (RFA vs. MWA: HR 7.861, 95% CI 1.642-37.635, p = 0.010) was an independent prognostic factor for LTP. We observed a significant interaction effect of ablation modality and type of peritumoral vessel on LTP (p = 0.034). For patients with periportal HCC, the LTP rate was significantly higher in the RFA group than in the MWA group (p = 0.045). However, this difference was not observed in patients with perivenous HCC (p = 0.116). CONCLUSIONS: In patients with a small single periportal HCC, MWA exhibited better tumor control than RFA. KEY POINTS: • Microwave ablation exhibited better local tumor control than radiofrequency ablation for small single periportal hepatocellular carcinoma. • There was a significant interaction between the treatment effect of ablation modality and type of peritumoral vessel on local tumor progression. • The type of peritumoral vessel is vital in choosing ablation modalities for hepatocellular carcinoma.

Oncolytic therapy and gene therapy for cancer: recent advances in antitumor effects of Newcastle disease virus.

Newcastle disease virus (NDV) replicates in the cytoplasm and disintegrates the host genome or participates in recombination, and has a strong affinity for tumor cells. These characteristics make it safer and more attractive than retroviruses or certain other DNA viruses, and one of the most potential oncolytic viruses used in oncolytic therapy. The construction of recombinant NDV (rNDV) using reverse genetics technology with NDV as a gene delivery vector has also enabled NDV in gene therapy approaches for treating cancer and other diseases. rNDV can not only stably express exogenous therapeutic genes, but also enhance the ability of the virus to kill tumor cells and induce host anti-tumor immune response. This article reviews the molecular characteristics, anti-tumor mechanisms, and the applications of NDV in cancer therapy.

Transarterial Chemoembolization Combined With Hepatectomy for the Treatment of Intermediate-Stage Hepatocellular Carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) is currently the recommended treatment for intermediate-stage hepatocellular carcinoma (HCC). Liver resection (LR) may be an effective option, although recurrences are not uncommon. TACE prior to LR has been proposed as an even better alternative. METHODS: Patients with intermediate-stage HCC who underwent curative resection were enrolled between January 2007 and December 2015. We compared overall survival (OS) and recurrence-free survival (RFS) for the 2 groups using the Kaplan-Meier method, and we determined independent risk factors for death and recurrence using multivariate regression analyses. RESULTS: A total of 488 patients with HCC at BCLC B (265 patients with LR, 223 patients with TACE+LR) enrolled from our center. Mean follow-up was 40.2 (range, 3.0-128.7) months. For patients receiving TACE+LR and LR, estimated 1-, 3-, and 5-year OS rates were 90.6% and 73.3%, 61.7% and 43.5%, and 52.9% and 33.8%, respectively (all P < 0.001) and estimated 1-, 2-, and 3-year RFS rates were 54.6% and 39.4%, 41.4% and 29.4%, and 36.3% and 26.3%, respectively (P < 0.001, P = 0.002, and P = 0.008, respectively). Significant independent predictors of poor OS were more than 3 (vs. 3 or fewer) tumors (HR=2.19, 95% CI 1.69-2.84), non-anatomical (vs. anatomical) hepatectomy (HR=1.29, 95% CI 1.01-1.66), microscopic vascular invasion (HR=1.46, 95% CI 1.15-.90), cirrhosis (HR=2.41, 95%CI 1.88-3.01), and intraoperative blood transfusion (HR=1.29, 95% CI 1.01-1.66). CONCLUSION: Preoperative TACE with LR may result in better oncological outcomes than either TACE or LR alone, without a substantial increase in morbidity, and could be considered an effective combination treatment for intermediate-stage HCC.

Assessment of Ablative Margin After Microwave Ablation for Hepatocellular Carcinoma Using Deep Learning-Based Deformable Image Registration.

Aim: To assess the ablative margin (AM) after microwave ablation (MWA) for hepatocellular carcinoma (HCC) with a deep learning-based deformable image registration (DIR) technique and analyze the relation between the AM and local tumor progression (LTP). Patients and Methods: From November 2012 to April 2019, 141 consecutive patients with single HCC (diameter ≤ 5 cm) who underwent MWA were reviewed. Baseline characteristics were collected to identify the risk factors for the determination of LTP after MWA. Contrast-enhanced magnetic resonance imaging scans were performed within 1 month before and 3 months after treatment. Complete ablation was confirmed for all lesions. The AM was measured based on the margin size between the tumor region and the deformed ablative region. To correct the misalignment, DIR between images before and after ablation was achieved by an unsupervised landmark-constrained convolutional neural network. The patients were classified into two groups according to their AMs: group A (AM ≤ 5 mm) and group B (AM > 5 mm). The cumulative LTP rates were compared between the two groups using Kaplan-Meier curves and the log-rank test. Multivariate analyses were performed on clinicopathological variables to identify factors affecting LTP. Results: After a median follow-up period of 28.9 months, LTP was found in 19 patients. The mean tumor and ablation zone sizes were 2.3 ± 0.9 cm and 3.8 ± 1.2 cm, respectively. The mean minimum ablation margin was 3.4 ± 0.7 mm (range, 0-16 mm). The DIR technique had higher AUC for 2-year LTP without a significant difference compared with the registration assessment without DL (P = 0.325). The 6-, 12-, and 24-month LTP rates were 9.9, 20.6, and 24.8%, respectively, in group A, and 4.0, 8.4, and 8.4%, respectively, in group B. There were significant differences between the two groups (P = 0.011). Multivariate analysis showed that being >65 years of age (P = 0.032, hazard ratio (HR): 2.463, 95% confidence interval (CI), 1.028-6.152) and AM ≤ 5 mm (P = 0.010, HR: 3.195, 95% CI, 1.324-7.752) were independent risk factors for LTP after MWA. Conclusion: The novel technology of unsupervised landmark-constrained convolutional neural network-based DIR is feasible and useful in evaluating the ablative effect of MWA for HCC.