A label-free and rapid fluorometric strategy for microRNA detection using CRISPR-Cas12a coupled with copper nanoparticles.

CRISPR-Cas12a with robust trans-cleavage activity were employed to mitigate background fluorescence signal, achieving sensitive detection of miRNA-21. The activation of trans-cleavage activity of Cas12a was achieved by utilizing cDNA as a trigger. Upon the presence of target miRNA-21, cDNA hybridizes with it forming a DNA/RNA double-stranded structure. Exonuclease III (ExoIII) facilitates the degradation of cDNA, releasing the target for subsequent cycles. Due to cDNA degradation, the trans-cleavage activity of Cas12a remains unactivated and does not disrupt the synthesis template of copper nanoparticles. Addition of Cu2+ and AA leads to the formation of highly fluorescent copper nanoparticles. Conversely, in absence of miRNA-21, intact cDNA activates trans-cleavage activity of Cas12a, resulting in degradation of the synthesis template and failure in synthesizing fluorescent copper nanoparticles. This method exhibits excellent selectivity with a low limit of detection (LOD) at 5 pM. Furthermore, we successfully applied this approach to determine miRNA-21 in cell lysates and human serum samples, providing a new approach for sensitive determination of biomarkers in biochemical research and disease diagnosis.

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.

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.

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.

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.

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.

"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.

Gold Nanoflares with Computing Function as Smart Diagnostic Automata for Multi-miRNA Patterns in Living Cells.

Investigating the multimolecule patterns in living cells is of vital importance for clinical and biomedical studies. Herein, we reported for the first time the engineering of gold nanoflares as smart automata to implement computing-based diagnosis in living mammalian cells. Defining the logic combinations of miR122 and miR21 as the detection patterns, the corresponding OR and AND diagnostic automata were designed. The results showed that they could recognize the correct patterns rapidly and sensitively. The automata could enter cells via self-delivery and have good biocompatibility. They enabled accurate diagnosis on miRNA signatures in different cell lines and differentiation of fluctuations in the same cell line at single cell resolution. Moreover, the automata afforded an innovative diagnostic mode. It simplified the complicated process of detecting, data-collecting, computing, and evaluating. The direct diagnosing result ("1" or "0") was exported according to the embedded computation code. It highlighted the new possibility of using smart automata for intelligent diagnostics and cancer therapy at single cell resolution.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Nomograms to predict survival outcomes after microwave ablation in elderly patients (>65 years old) with early-stage hepatocellular carcinoma.

Objectives: To develop and validate the nomograms to predict survival outcomes after microwave ablation (MWA) in elderly patients(>65 years old) with early-stage hepatocellular carcinoma (EHCC).Methods: This retrospective study was approved by the institutional review board. A total of 265 EHCC patients (76 females, 189 males; average age 71.4 years ± 5.4 [standard deviation]) with 345 nodules subsequently underwent MWA from April 2006 to October 2019. Baseline characteristics were collected to identify the risk factors for the determination of survival outcomes after MWA. The nomograms were based on prognostic factors for overall survival (OS) and recurrence-free survival (RFS) from the multivariate Cox proportional hazards model and validated in external cohorts from another two institutions (n = 130). The nomograms were assessed for their predictive accuracy using Harrell's concordance index (C-index).Results: After a median follow-up time of 28.6 months, 29.8% (79/265) of the patients died, and 54.3% (144/265) of the patients experienced recurrence in the training set. The OS nomogram was developed based on the hepatitis B virus (HBV) presence, α-fetoprotein (AFP), and albumin, with a C-index of 0.757 (95% confidence interval [CI]: 0.645, 0.789).The scores of the nomogram ranged from 0 to 24. The RFS nomogram was developed based on tumor number, abutting major vessels and platelets, with a C-index of 0.733 (CI: 0.672, 0.774). The likelihood of 3- and 5-year OS and RFS were consistent between clinical observations and nomogram predictions in external cohorts.Conclusions: The nomogram models can be useful in determining the risk of OS and RFS in elderly patients with EHCC after MWA, which can guide individual patient management.Key pointsMWA is an effective and feasible treatment for elderly patients with EHCC and can improve survival outcomes.A calibrated and objective nomogram model for the prediction of survival outcomes in elderly patients (>65 years old) may guide patient selection and MWA treatment.Older age was not deemed to be a risk factor for survival outcomes when the elderly patients with EHCC underwent MWA.

Recombinant Fusion Streptavidin as a Scaffold for DNA Nanotetrads for Nucleic Acid Delivery and Telomerase Activity Imaging in Living Cells.

Efficient platforms for intracellular delivery of nucleic acids are essential for biomedical imaging and gene regulation. We develop a recombinant fusion streptavidin as a novel protein scaffold for DNA nanotetrads for highly efficient nucleic acid delivery and telomerase activity imaging in living cells via cross-linking hybridization chain reaction (cHCR). The recombinant streptavidin protein is designed to fuse with multiple SV40 NLS (nuclear localization signal) and NES (nuclear export signal) domains and prepared through Escherichia coli expression. The recombinant NLS-SA protein allows facile assembly with four biotinylated DNA probes via high-affinity noncovalent interactions, forming a well-defined DNA tetrad nanostructure. The DNA nanotetrads are demonstrated to confer efficient cytosolic delivery of nucleic acid via a caveolar mediated endocytosis pathway, allowing efficient escape from lysosomal degradation. Moreover, the nanotetrads enable efficient cHCR assembly in response to telomerase in vitro and in cellulo, affording ultrasensitive detection and spatially resolved imaging for telomerase with a detection limit as low as 90 HeLa cells/mL. The fluorescence brightness obtained in live cell imaging is found to be dynamically correlated to telomerase activity and the inhibitor concentrations. Therefore, the proposed strategy may provide a highly efficient platform for nucleic acid delivery and imaging of biomarkers in living cells.

Radiofrequency Ablation Following Downstaging of Hepatocellular Carcinoma by Using Transarterial Chemoembolization: Long-term Outcomes.

Background Transarterial chemoembolization (TACE) is an effective downstaging procedure for hepatocellular carcinoma (HCC). However, knowledge of the effectiveness of radiofrequency ablation (RFA) after downstaging of HCC is currently lacking. Purpose To evaluate the clinical outcomes of RFA after downstaging of HCC by using TACE. Materials and Methods This retrospective study investigated a cohort of patients who underwent RFA with curative intent after downstaging with TACE to meet Milan criteria (one lesion up to 5 cm or no more than three lesions ≤3 cm without vascular invasion or extrahepatic metastasis) from January 2012 to July 2017. A control group of patients initially meeting the Milan criteria also underwent RFA as first-line treatment in the same period. Overall survival (OS), disease-free survival (DFS), and major complication rates were compared by using the log-rank test. To reduce potential bias, a propensity score analysis was also performed. Results There were 72 patients (median age, 56.5 years; range, 30-78 years; 67 men) in the downstaging group and 357 patients meeting the Milan criteria (median age, 58.0 years; range, 25-87 years; 313 men) included in this study. After propensity score matching, the 1-, 3-, and 5-year OS rates were 99%, 80%, and 66%, respectively, for the patients in the downstaging group and 94%, 84%, and 69%, respectively, for the patients in the Milan criteria group. The 1-, 3-, and 5-year DFS rate were 73%, 34%, and 24% for the downstaging group and 74%, 43%, and 37% for the Milan criteria group. There were no differences in the OS, DFS, or major complication rates between the two groups (P = .74, P = .39, P = .73, respectively). Conclusion The long-term patient survival and major complication rates of radiofrequency ablation following transarterial chemoembolization downstaging for hepatocellular carcinoma were similar to that of patients initially meeting the Milan criteria. © RSNA, 2019 See also the editorial by vanSonnenberg and Mueller in this issue.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

A Stable Lithium-Oxygen Battery Electrolyte Based on Fully Methylated Cyclic Ether.

Ether-based electrolytes are commonly used in Li-O2 batteries (LOBs) because of their relatively high stability. But they are still prone to be attacked by superoxides or singlet oxygen via hydrogen abstract reactions, which leads to performance decaying during long-term operation. Herein we propose a methylated cyclic ether, 2,2,4,4,5,5-hexamethyl-1,3-dioxolane (HMD), as a stable electrolyte solvent for LOBs. Such a compound does not contain any hydrogen atoms on the alpha-carbon of the ether, and thus avoids hydrogen abstraction reactions. As the result, this solvent exhibits excellent stability with the presence of superoxide or singlet oxygen. In addition the CO2 evolution during charge process is prohibited. The LOB with HMD-based electrolyte was able to run up to 157 cycles, 4 times more than with 1,3-dioxolane (DOL) or 1,2-dimethoxyethane (DME) based electrolytes.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Proton-Fueled, Reversible DNA Hybridization Chain Assembly for pH Sensing and Imaging.

Design of DNA self-assembly with reversible responsiveness to external stimuli is of great interest for diverse applications. We for the first time develop a pH-responsive, fully reversible hybridization chain reaction (HCR) assembly that allows sensitive sensing and imaging of pH in living cells. Our design relies on the triplex forming sequences that form DNA triplex with toehold regions under acidic conditions and then induce a cascade of strand displacement and DNA assembly. The HCR assembly has shown dynamic responses in physiological pH ranges with excellent reversibility and demonstrated the potential for in vitro detection and live-cell imaging of pH. Moreover, this method affords HCR assemblies with highly localized fluorescence responses, offering advantages of improving sensitivity and better selectivity. The proton-fueled, reversible HCR assembly may provide a useful approach for pH-related cell biology study and disease diagnostics.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

BACKGROUND: It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. METHODS: One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. RESULTS: One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). CONCLUSIONS: This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Internal jugular vein versus subclavian vein as the percutaneous insertion site for totally implantable venous access devices: a meta-analysis of comparative studies.

BACKGROUND: A totally implantable venous access device (TIVAD) provides reliable, long-term vascular access and improves patients' quality of life. The wide use of TIVADs is associated with important complications. A meta-analysis was undertaken to compare the internal jugular vein (IJV) with the subclavian vein (SCV) as the percutaneous access site for TIVAD to determine whether IJV has any advantages. METHODS: All randomized controlled trials (RCTs) and cohort studies assessing the two access sites, IJV and SCV, were retrieved from PubMed, Web of Science, Embase, and OVID EMB Reviews from their inception to December 2015. Random-effects models were used in all analyses. The endpoints evaluated included TIVAD-related infections, catheter-related thrombotic complications, and major mechanical complications. RESULTS: Twelve studies including 3905 patients published between 2008 and 2015, were included. Our meta-analysis showed that incidences of TIVAD-related infections (odds ratio [OR] 0.71, 95 % confidence interval [CI] 0.48-1.04, P = 0.081) and catheter-related thrombotic complications (OR 0.76, 95 % CI 0.38-1.51, P = 0.433) were not significantly different between the two groups. However, compared with SCV, IJV was associated with reduced risks of total major mechanical complications (OR 0.38, 95 % CI 0.24-0.61, P < 0.001). More specifically, catheter dislocation (OR 0.43, 95 % CI 0.22-0.84, P = 0.013) and malfunction (OR 0.42, 95 % CI 0.28-0.62, P < 0.001) were more prevalent in the SCV than in the IJV group; however, the risk of catheter fracture (OR 0.47, 95 % CI 0.21-1.05, P = 0.065) were not significantly different between the two groups. Sensitivity analyses using fixed-effects models showed a decreased risk of catheter fracture in the IJV group. CONCLUSION: The IJV seems to be a safer alternative to the SCV with lower risks of total major mechanical complications, catheter dislocation, and malfunction. However, a large-scale and well-designed RCT comparing the complications of each access site is warranted before the IJV site can be unequivocally recommended as a first choice for percutaneous implantation of a TIVAD.