An evaluation of 20-year survival of radiofrequency ablation for hepatocellular carcinoma as first-line treatment.

OBJECTIVES: To evaluate the changes in clinical characteristics, overall survival (OS), and progression-free survival (PFS) by investigating a 20-year cohort of patients with HCC who underwent RFA treatment. METHODS: From 2000 to 2020, 505 consecutive patients with HCC underwent ultrasound-guided percutaneous RFA as first-line therapy at a tertiary cancer hospital. We divided the cohort according to the time when hepatitis-B antiviral therapy was covered by national medical insurance coverage (early 2011), including the first decade (2000-2010) and second decade (2011-2020). The prognostic factors for OS were analyzed by the Cox proportional hazard model. OS and PFS in different groups were compared using the Kaplan-Meier method. To reduce selection bias, matched groups of patients were selected using the propensity score matching (PSM) method. RESULTS: In total, 726 RFA sessions were performed to treat 867 HCC lesions. Patients treated in the second decade were younger (p =.047), had smaller tumors (p <.001), had lower Child-Pugh scores (p <.001), and had a higher proportion of antiviral treatment (p <.001). A total of 96.0% of patients achieved technical efficacy from the initial RFA. After PSM analysis, improved PFS was found for the second decade (median, 68 vs. 49 months, p =.003), but no significant difference in OS was observed between the two groups (median, 71 vs. 65 months, p =.20). CONCLUSIONS: This study demonstrated that improved PFS was achieved in patients with HCC receiving RFA as first-line treatment in the second decade. However, long-term OS was not significantly increased compared to the first decade suggesting that while RFA treatment has improved, it still might not substantially affect OS results.

The Role of Contrast-Enhanced Ultrasound Plus Color Parametric Imaging in the Differential Diagnosis of Subpleural Pulmonary Lesions.

OBJECTIVES: To distinguish benign and malignant subpleural pulmonary lesions (SPLs) with contrast-enhanced ultrasound (CEUS) and color parametric imaging (CPI), and evaluate the role of CEUS plus CPI in the differential diagnosis of pathological types of SPLs. METHODS: One hundred and thirty-six patients underwent CEUS with a Logiq E9 XD Clear ultrasonic machine equipped with a 3.5- to 5.0-MHz C5-1 transducer in our center were enrolled in our study, including 27 cases of benign lesions and 109 cases of malignant lesions. The ultrasound contrast agent used in this study was SonoVue. CEUS images and CPI of all cases were reviewed and analyzed by the resident and staff radiologist groups separately. RESULTS: With CEUS alone, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while centripetal enhancement pattern occurred more frequently in malignant SPLs (P < .001). With CEUS plus CPI, by both the two groups, the main enhancement pattern of benign SPLs was arborization (P < .001), while those of malignant SPLs were centripetal (P < .001) and eccentric (P < .05). The diagnosis performance of CEUS plus CPI was significantly higher than that of CEUS alone in both the resident (area under the curve [AUC] = 0.857 vs 0.677, P < .001) and staff (AUC = 0.866 vs 0.681, P < .001) groups. Moreover, CPI offered remarkable inter-consistency improvements in the enhancement pattern determination between the two groups. CONCLUSION: The CEUS enhancement patterns would provide information of blood perfusion patterns in the differential diagnosis of benign and malignant SPLs. The diagnosis performance could be significantly improved by CEUS plus CPI compared with CEUS alone.

Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition.

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)-induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be -11.2 and -6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

Integrating the microneedles with carboplatin to facilitate the therapeutic effect of radiotherapy for skin cancers.

In most skin cancer patients, excisional surgery is required to remove tumorous tissue. However, the risk of locoregional recurrence after surgery alone is relatively high, particularly for a locally advanced stage of melanoma. Therefore, additional adjuvant treatments, such as radiotherapy, can be used after surgery to inhibit recurrent melanoma after surgical removal. To enhance local radiotherapy, we present the combined X-ray radiation and radiosensitizers (carboplatin) through microneedles (MNs) to treat melanoma. The MNs could be beneficial to precisely delivering carboplatin into the sub-epidermal layer of the melanoma region and alleviate patients' fear and discomfort during the drug administration compared to the traditional local injection. The carboplatin was loaded into the tips of dissolving gelatin MNs (carboplatin-MNs) through the molding method. The results show gelatin MNs have sufficient mechanical strength and can successfully administer carboplatin into the skin. Both in vitro and in vivo studies suggest that carboplatin can enhance radiotherapy in melanoma treatment. With a combination of radiotherapy and carboplatin, the inhibition effect of carboplatin delivered into the B16F10 murine melanoma model through MNs administration (1.2 mg/kg) is equivalent to that through an intravenous route (5 mg/kg). The results demonstrate a promise of combined carboplatin and X-ray radiation treatment in treating melanoma by MNs administration.

Percutaneous Radiofrequency Ablation Is an Effective Method for Local Control of Liver Metastases From Lung Cancer.

Objective: To investigate the clinical value of percutaneous radiofrequency ablation (RFA) for liver metastasis from lung cancer (LCLM). Materials and Methods: We retrospectively enrolled 58 patients who underwent RFA for LCLM between January 2014 and December 2019. Primary lung cancer histology included 38 adenocarcinomas, 15 squamous carcinomas, and 5 small cell carcinomas. For 83 metastatic lesions (mean tumor diameter 3.3 ± 1.1 cm, range 0.9-5.0 cm), 65 RFA sessions were performed. Before RFA, 17 and 41 patients presented no and stable extrahepatic metastasis, respectively, whereas 18 and 40 patients had synchronous and metachronous liver metastasis, respectively. Survival was analyzed using the Kaplan-Meier method. Cox proportional hazards model was used for multivariable analysis. Results: The technical success rate was 96.3% (80/83 lesions). Local tumor progression was observed in 8 (9.8%, 8/82) lesions of 57 (14.0%, 8/57) patients at 4-12 months after RFA. New liver metastases occurred in 27 (46.6%) patients. The overall survival (OS) rates at 1, 2, 3, and 5 years after RFA were 55.2%, 26.0%, 22.0%, and 14.4%, respectively. The median OS after RFA and after liver metastasis were 14.0 ± 1.6 and 20.0 ± 1.5 months, respectively. Based on the univariable analysis, tumor size (p=0.017), histological type (p=0.015), and timing of liver metastasis (p=0.046) were related to OS. In further multivariable analyses, squamous carcinoma (hazard ratio= 2.269, 95% confidence interval: 1.186-4.339, p=0.013) was an independent unfavorable prognostic factor for OS. Based on the univariable analysis, histological type (p=0.010) was identified as parameters significantly related to local tumor progression (LTP)-free survival. Further multivariable analyses revealed that squamous carcinoma (hazard ratio=2.394, 95% confidence interval: 1.260-4.550, p=0.008) was an independent unfavorable prognostic factor for LTP-free survival. Conclusion: RFA is a safe therapeutic option for LCLM with acceptable local tumor control, especially in patients with a tumor size ≤3 cm, adenocarcinoma/small cell carcinoma, and metachronous liver metastases.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastasis from pancreatic adenocarcinoma.

OBJECTIVE: To analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for pancreatic adenocarcinoma liver metastasis (PALM). METHODS: Between January 2010 and July 2021, 20 patients (13 males) with an average age of 58.9 ± 11.7 years who underwent RFA for PALM were included. The mean maximum diameter of PALMs was 2.6 ± 1.1 cm (1.0-6.0 cm). Survival curves were built using the Kaplan-Meier method and compared by the log-rank test. Multivariable analyses were performed by using the Cox proportional hazards model. RESULTS: Twenty patients with 29 PALMs underwent 23 RFA sessions. Technical efficacy was achieved in 28 PALMs (28/29, 96.6%). The mean overall survival (OS) after RFA was 14.6 months and the 1-, 2-year survival rates were 39.5%, 18.1%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.023) and extrahepatic metastasis before RFA (p = 0.038) were identified as independent prognostic factors for OS in patients with PALM. Additionally, the mean progression-free survival (PFS) after RFA was 11.5 months and 1-, 2- year survival rates were 26.0%, 17.3%, respectively. With multivariate analysis, abnormal serum levels of CA199 (p = 0.016) and extrahepatic metastasis before RFA (p = 0.043) were also identified as independent prognostic factors for PFS in patients with PALM. CONCLUSION: RFA is a safe and effective treatment for patients with PALM, especially in patients with normal serum level of CA199 or the patients without extrahepatic metastases before RFA.

Role of Bioactive Constituents of Panax notoginseng in the Modulation of Tumorigenesis: A Potential Review for the Treatment of Cancer.

Cancer is a leading cause of death, affecting people in both developed and developing countries. It is a challenging disease due to its complicated pathophysiological mechanism. Many anti-cancer drugs are used to treat cancer and reduce mortality rates, but their toxicity limits their administration. Drugs made from natural products, which act as multi-targeted therapy, have the ability to target critical signaling proteins in different pathways. Natural compounds possess pharmacological activities such as anti-cancer activity, low toxicity, and minimum side effects. Panax notoginseng is a medicinal plant whose extracts and phytochemicals are used to treat cancer, cardiovascular disorders, blood stasis, easing inflammation, edema, and pain. P. notoginseng's secondary metabolites target cancer's dysregulated pathways, causing cancer cell death. In this review, we focused on several ginsenosides extracted from P. notoginseng that have been evaluated against various cancer cell lines, with the aim of cancer treatment. Furthermore, an in vivo investigation of these ginsenosides should be conducted to gain insight into the dysregulation of several pathways, followed by clinical trials for the potential and effective treatment of cancer.

Severe interstitial pneumonia caused by cetuximab: a case report and review of the literature.

Cetuximab is an IgG1 chimeric mAb against epidermal growth factor receptor, which can be used for chemotherapy failure or tolerance in patients with epidermal growth factor receptor expressed RAS wild-type metastatic colorectal cancer. We report on a patient who developed rapid-onset interstitial pneumonia while being treated with cetuximab plus XELOX (oxaliplatin, capecitabine) for metastatic colorectal cancer. A 75-year-old man patient was administered cetuximab plus XELOX regularly. After his cetuximab schedule was adjusted from 1 to 2 weeks, he rapidly developed interstitial pneumonia which led to acute respiratory distress syndrome. Our literature review indicated that, for patients with risk factors, a 2-week regimen of cetuximab might lead to interstitial pneumonia. Clinicians should closely monitor patients for adverse drug reactions to improve drug safety.

The 10-year Survival Analysis of Radiofrequency Ablation for Solitary Hepatocellular Carcinoma 5 cm or Smaller: Primary versus Recurrent HCC.

Background Although favorable outcomes have been reported with radiofrequency ablation (RFA) for limited hepatocellular carcinoma (HCC), the efficacy of this treatment for recurrent HCC has not been thoroughly investigated. Purpose To compare the long-term outcomes and analyze the prognostic factors for outcomes after RFA for initial HCC versus as a second-line treatment for recurrent HCC. Materials and Methods This retrospective study included 560 patients with solitary tumors 5 cm or smaller (263 initial HCCs, 297 -recurrent HCCs) who underwent percutaneous US-guided RFA from January 2005 to December 2016. Of 297 patients with -recurrent HCC, 134 had previously undergone hepatectomy, 128 had undergone transarterial chemoembolization (TACE), and 35 had undergone local ablation therapy. Overall survival (OS) between initial HCC and recurrent HCC was compared before and after propensity score matching. Prognostic factors for all patients were analyzed with the log-rank test and Cox proportional hazards model. Results A total of 560 patients (mean age, 60 years ± 12 [standard deviation]; 441 men) were evaluated. Before matching, the OS rates at 1, 3, 5, and 10 years were 92.6%, 73.9%, 59.3%, and 39.6%, respectively, in patients with recurrent HCC and 92.8%, 75.4%, 63.3%, and 44.7% in patients with initial HCC (P = .27). After matching, the OS rates at 1, 3, 5, and 10 years were 94.8%, 75.7%, 61.6%, and 47.3% in the initial HCC group and 91.9%, 71.2%, 58.7%, and 45.2% in the recurrent HCC group (P = .32). Among patients with recurrent HCC, no significant difference in mean OS was noted for local recurrence versus distant recurrence (81.6 months ± 5.1 vs 83.8 months ± 6.6, P = .82) or previous treatment modality (82.0 months ± 7.3 in the resection group, 82.7 months ± 5.3 in the TACE group, and 79.3 months ± 10.8 in the local ablation group; P = .83). Local tumor progression after previous local ablation (10 of 35 [28.6%]) was higher than that after previous hepatectomy (15 of 134 [11.2%], P = .04). Multivariable analysis demonstrated that tumor size (hazard ratio, 1.58; 95% CI: 1.06, 2.36; P = .02), portal hypertension (hazard ratio, 1.52; 95% CI: 1.03, 2.26; P = .04), Child-Pugh class (hazard ratio, 2.01; 95% CI: 1.02, 3.96; P = .045), and serum α-fetoprotein level (hazard ratio, 1.62; 95% CI: 1.10, 2.39; P = .01) were independent predictive factors for recurrent HCC outcomes. Conclusion Radiofrequency ablation provides similar long-term survival for solitary hepatocellular carcinoma of 5 cm or less, regardless of whether treatment is initial or salvage therapy. © RSNA, 2021 Online supplemental material is available for this article.

A Perspective on Imiquimod Microneedles for Treating Warts.

Warts are a common skin problem and are caused by infection with a virus. Warts are currently mainly treated by therapies involving ablating tissue or interrupting cellular division. However, all these existing treatments are either invasive or cause skin pain and tissue destruction. Imiquimod is a synthetic compound that belongs to the imidazoquinolinone family. It has been successfully used as a topical drug to treat external anogenital warts. However, topical imiquimod cream for warts is restricted by low skin permeability, and several side effects such as itching, pain, and erosions occur most frequently following topical treatment. Microneedle technology, a minimally invasive drug delivery system, has the potential to overcome the barrier of the stratum corneum. This technique would also offer a painless treatment choice and provide personalized therapies. In the study, we loaded imiquimod within dissolving microneedles using the molding method. Gelatin was used as a structural material for microneedle formation without adding a crosslinker. To our knowledge, this is the first study of using dissolving microneedles and exploring their utilization with imiquimod for the treatment of warts. First, we added fluorescent dye and trypan blue into the microneedles to evaluate the status of drugs in the microneedles and the degradation property of microneedles made of gelatin, respectively. Here we also prove the strength of the imiquimod microneedles and study their capability to penetrate the skin. The results show no apparent differences in mechanical failure after an additional imiquimod-loaded. Besides, we provide evidence that imiquimod microneedles induce secreted embryonic alkaline phosphatase (SEAP) in the RAW 264.7 macrophages. Gelatin does not affect the imiquimod in microneedles; a similar immune response was affected by the imiquimod alone or imiquimod complexed with gelatin. Our research demonstrates a proof of concept of using imiquimod microneedles for future warts treatment.

Impact of Zr-Doped Bi2O3 Radiopacifier by Spray Pyrolysis on Mineral Trioxide Aggregate.

Mineral trioxide aggregates (MTA) have been developed as a dental root repair material for a range of endodontics procedures. They contain a small amount of bismuth oxide (Bi2O3) as a radiopacifier to differentiate adjacent bone tissue on radiographs for endodontic surgery. However, the addition of Bi2O3 to MTA will increase porosity and lead to the deterioration of MTA's mechanical properties. Besides, Bi2O3 can also increase the setting time of MTA. To improve upon the undesirable effects caused by Bi2O3 additives, we used zirconium ions (Zr) to substitute the bismuth ions (Bi) in the Bi2O3 compound. Here we demonstrate a new composition of Zr-doped Bi2O3 using spray pyrolysis, a technique for producing fine solid particles. The results showed that Zr ions were doped into the Bi2O3 compound, resulting in the phase of Bi7.38Zr0.62O12.31. The results of materials analysis showed Bi2O3 with 15 mol % of Zr doping increased its radiopacity (5.16 ± 0.2 mm Al) and mechanical strength, compared to Bi2O3 and other ratios of Zr-doped Bi2O3. To our knowledge, this is the first study of fabrication and analysis of Zr-doped Bi2O3 radiopacifiers through the spray pyrolysis procedure. The study reveals that spray pyrolysis can be a new technique for preparing Zr-doped Bi2O3 radiopacifiers for future dental applications.

Viroinformatics-Based Analysis of SARS-CoV-2 Core Proteins for Potential Therapeutic Targets.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus for which no known effective antiviral drugs are available. In the present study, to accelerate the discovery of potential drug candidates, bioinformatics-based in silico drug discovery approaches are utilized. We performed multiple sequence alignments of the Spike (S) protein with 75 sequences of different viruses from the Orthocoronavirinae subfamily. This provided us with insights into the evolutionarily conserved domains that can be targeted using drugs or specific antibodies. Further, we analyzed the mechanism of SARS-CoV-2 core proteins, i.e., S and RdRp (RNA-dependent RNA polymerase), to elucidate how the virus infection can utilize hemoglobin to decrease the blood oxygen level. Moreover, after a comprehensive literature survey, more than 60 antiviral drugs were chosen. The candidate drugs were then ranked based on their potential to interact with the Spike and RdRp proteins of SARS-CoV-2. The present multidimensional study further advances our understanding of the novel viral molecular targets and potential of computational approaches for therapeutic assessments. The present study can be a steppingstone in the selection of potential drug candidates to be used either as a treatment or as a reference point when designing a new drug/antibody/inhibitory peptide/vaccine against SARS-CoV-2.

Differentiation of atypical hepatic hemangioma from liver metastases: Diagnostic performance of a novel type of color contrast enhanced ultrasound.

BACKGROUND: In clinical practice, the diagnosis is sometimes difficult with contrast-enhanced ultrasound (CEUS) when the case has an atypical perfusion pattern. Color parametric imaging (CPI) is an analysis software for CEUS with better detection of temporal differences in CEUS imaging using arbitrary colors. It measures the differences in arrival time of the contrast agent in lesions so that the perfusion features of atypical hemangioma and colorectal cancer (CRC) liver metastasis can be distinguished. AIM: To evaluate the role of a novel type of CPI of CEUS in the differential diagnosis of atypical hemangioma from liver metastases in patients with a history of CRC. METHODS: From January 2016 to July 2018, 42 patients including 20 cases of atypical hemangioma and 22 cases of liver metastases from CRC were enrolled. These patients had a mean age of 60.5 ± 9.3 years (range: 39-75 years). All patients received ultrasound, CEUS and CPI examinations. Resident and staff radiologists independently and retrospectively reviewed CEUS and CPI images. Two sets of criteria were assigned: (1) Routine CEUS alone; and (2) CEUS and CPI. The diagnostic sensitivity, specificity, accuracy and receiver operating characteristic (ROC) curve of resident and staff radiologists were analyzed. RESULTS: The following CPI features were significantly different between liver hemangioma and liver metastases analyzed by staff and resident radiologists: Peripheral nodular enhancement (65%-70.0% vs 4.5%-13.6%, P < 0.001, P = 0.001), mosaic/chaotic enhancement (5%-10% vs 68.2%-63.6%, P < 0.001, P < 0.001) and feeding artery (20% vs 59.1%-54.5%, P = 0.010, P = 0.021). CPI imaging offered significant improvements in detection rates compared with routine CEUS in both resident and staff groups. By resident radiologists, the specificity and accuracy of CEUS+CPI were significantly increased compared with that of CEUS (77.3% vs 45.5%, P = 0.030; 78.6% vs 50.0%, P = 0.006). In addition, the area under the curve (AUC) of CEUS+CPI was significantly higher than that of CEUS (0.803 vs 0.757, P = 0.036). By staff radiologists, accuracy was improved in CEUS+CPI (81.0% vs 54.8%, P = 0.010), whereas no significant differences in specificity and sensitivity were found (P = 0.144, P = 0.112). The AUC of CEUS+CPI was significantly higher than that of CEUS (0.890 vs 0.825, P = 0.013) by staff radiologists. CONCLUSION: Compared with routine CEUS, CPI could provide specific information on the hemodynamic features of liver lesions and help to differentiate atypical hemangioma from liver metastases in patients with CRC, even for senior radiologists.

Thermosensitive liposomal doxorubicin plus radiofrequency ablation increased tumor destruction and improved survival in patients with medium and large hepatocellular carcinoma: A randomized, double-blinded, dummy-controlled clinical trial in a single center.

BACKGROUND: Lyso-thermosensitive liposomal doxorubicin (LTLD, ThermoDox) consists of doxorubicin encapsulated contained within a heat-sensitive liposome. AIMS AND OBJECTIVES: We sought to evaluate whether the use of combined radiofrequency ablation (RFA) and LTLD would result in larger coagulation volume and longer overall survival (OS) compared with the use of RFA alone in patients with 3-7 cm unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between 2010 and 2012, 22 HCC patients were randomly assigned to one of two treatments in our center: (1) ultrasound-guided percutaneous RFA plus intravenous (IV) infusion of LTLD (combination, n = 11) or (2) RFA plus IV dummy (RFA, n = 11). Four patients withdrew from the study, and the remaining 18 patients entered the final analysis. There were 14 male and 4 female patients with an average age of 61.1 ± 9.3 years (range: 40-73 years). The average tumor size was 4.2 ± 1.0 cm (range: 3.1-6.1 cm). One-month enhanced computed tomography was used to evaluate the ablation efficacy and coagulation volume after RFA. Regular follow-up after RFA was performed to assess toxicity, local response rates, and OS rates. RESULTS: A major complication (empyema) occurred in one case in the combination group. Combination treatment region did not induce any additional toxicity beyond doxorubicin. The primary ablation success rate was 93.3% (14/15 tumors) in the combination group and 77.8% (7/9 tumors) in the RFA group (P = 0.308). The difference in coagulation volume between pre- and post-RFA in the combination group was significantly larger than that of the RFA group (105.7 ± 73.8 cm 3 vs. 37.3 ± 8.5 cm 3, P = 0.013). The follow-up period ranged from 11 to 80 months (average: 49.1 ± 24.8 months). The local progression rate was 6.7% (1/15 tumors) in the combination group and 22.2% (2/9 tumors) in the RFA group. The mean OS for the combination group was 68.5 ± 7.2 months, which was significantly greater compared with the RFA group (46.0 ± 10.6 months, P = 0.045). CONCLUSIONS: RFA with heat target delivery chemotherapy facilitated better tumor coagulation necrosis without additional toxicity. This combined treatment may improve the clinical efficacy of RFA or free doxorubicin and prolong survival in patients with medium to large HCC.

The Synthesis and Characterization of PEG-SH-Modified Gold Nanoparticle in One-Pot Synthesis by Stenotrophomonas maltophilia.

Colloidal gold nanoparticles have been researched and utilized in many technical applications. However, the conventionalmethods to produce polyethyleneglycol (PEG) immobilized gold nanoparticles have to take several steps, including residual solvent removing. In the study, we propose an idea green route to synthesize gold nanoparticles by using Stenotrophomonas maltophilia in a one-pot reaction. The relationship between Au precursor and S. maltophilia was evaluated systematically. After PEG-SH addition, the bacterial cell wall was broken down and the synthetic nanoparticles could be released into culture medium. Furthermore, we identified that the crystal structure of synthetic gold nanoparticle was face-center cubic and PEG-SH was immobilized on synthetic gold nanoparticle ideally. The size of Au-PEG-SH was smaller than 30 nm. These findings suggest that gold nanoparticle with PEG-SH modification could be prepared in an eco-friendly one-pot reaction through the metabolic activity of S. maltophilia.

Regulation of Fn14 stability by SCFFbxw7α during septic acute kidney injury.

Acute kidney injury (AKI) initiated by sepsis remains a thorny problem despite recent advancements in its clinical management. Having been found to be activated during AKI, fibroblast growth factor-inducible molecule 14 (Fn14) may be a potential therapeutic target because of its involvement in the molecular basis of injury. Here, we report that LPS induces apoptosis of mouse cortical tubule cells mediated by Fn14, for which simultaneous Toll-like receptor (TLR)4 activation is required. Mechanistically, TLR4 activation by lipopolysaccharide, through disassociating E3 ligase SCFFbxw7α from Fn14, dismantles Lys48-linked polyubiquitination of Fn14 and stabilizes it. Pharmacological deactivation of Fn14 with monoclonal antibody ITEM-2 provides effective protection against lethal sepsis and AKI in mice. Our study underscores an adaptive mechanism whereby TLR4 regulates SCFFbxw7α-dependent Fn14 stabilization during inflammatory tubular damage and further supports investigation of targeting Fn14 in clinical trials of patients with septic AKI.

Productive transcription of miR-124-3p by RelA and RNA polymerase II directs RIP1 ubiquitination-dependent apoptosis resistance during hypoxia.

The K63-linked ubiquitination of RIP1 coordinates survival/death homeostasis by driving transcription of genes downstream of RelA. Previously, we demonstrated that EGF-dependent RelA transactivation overcomes hypoxia-initiated apoptosis, yet the underlying mechanisms remain mysterious. We report here that UBXN1 deficiency empowers apoptosis resistance against hypoxia through triggering IκBα degradation, for which K63-linked ubiquitination of RIP1 is required. MiR-124-3p is a bona fide inhibitor upstream of UBXN1, thereby antagonizing the hypoxia-initiated apoptosis. UBXN1 repression by miR-124-3p restores the K63-linked ubiquitination of RIP1, IKKß phosphorylation, IκBα-RelA disassembly, RelA nuclear localization and transactivation of EGF gene as well as EGF secretion under hypoxia. Reconstitution of wild-type UBXN1, but not a truncated UBXN1ΔUBA mutant, or pharmacological inhibition of RelA transactivation in miR-124-3p-replete cells compromises the apoptosis-resistant phenotypes of miR-124-3p. Hypoxia transcriptionally downregulates miR-124-3p by disassociating RelA and RNAP II from its promoter. EGFR activation renders the K63-linked ubiquitination of RIP1 and hypoxic tolerance in conjunction with miR-124-3p. Our findings identify a pivotal role of miR-124-3p in ubiquitin conjugation of RIP1 against hypoxic damage and underscore that productive transcription of miR-124-3p by RelA and RNAP II might be a switching mechanism for this process.

The Role of a Curved Electrode with Controllable Direction in the Radiofrequency Ablation of Liver Tumors Behind Large Vessels.

PURPOSE: To investigate the role of a novel curved radiofrequency ablation (RFA) electrode with controllable direction in the ablation of tumors behind large hepatic vessels in ex vivo bovine and in vivo canine liver experiments. MATERIALS AND METHODS: Approval from the institutional animal care and use committee was obtained. In ex vivo experiments, conventional multi-tines expandable electrodes, conventional monopolar straight electrodes and novel curved electrodes were used in the ablation of the bovine liver (n = 90). The ablated area, parallel axis, vertical axis and shape of different electrodes were compared. Then, 24 beagle dogs (10 months old, female) were used for in vivo experiments. Visual tumor targets deeply located in the portal vein were established, and ultrasound-guided liver ablation was performed with different electrodes. The ablation range, target coverage rate, percentage of normal tissue injury and damage to adjacent vessels were evaluated. The Kruskal-Wallis test and the Chi-squared test were used for statistical analysis. RESULTS: For the ex vivo study with a 3-cm electrode, the ablation area of the multi-tines expandable electrode group (7.14 ± 0.16 cm2) was significantly larger than that of the novel curved electrode group (5.01 ± 0.30 cm2, P < 0.001) and the monopolar straight electrode group (5.43 ± 0.15 cm2, P < 0.001). The results obtained with the 4-cm electrode in the three groups were in accordance with those of the 3-cm electrode. In vivo, the normal tissue damage area of the novel curved electrode group was smaller than that of the multi-tines expandable electrode group (1.10 ± 0.18 cm2 vs. 4.00 ± 0.18 cm2, P < 0.001). The target coverage rate of the novel curved electrode group was better than that of the monopolar straight electrode group (100% vs. 80.86 ± 1.68%, P < 0.001). The hematoxylin and eosin (H&E) and TUNEL staining results showed that the ablation necrosis area was adjacent to large vessels, but the vascular wall was not significantly damaged in the novel curved electrode group. CONCLUSION: Our preliminary results showed that the novel curved RFA electrode with controllable direction could achieve accurate ablation for tumors behind large hepatic vessels, with a better target coverage rate and less damage to normal tissue, than conventional multi-tines expandable electrodes and monopolar straight electrodes.

The value of KRAS gene status in predicting local tumor progression of colorectal liver metastases following radiofrequency ablation.

PURPOSE: We investigated the relationships between KRAS gene status and local tumor progression (LTP) of colorectal liver metastases (CLMs) after treatment with percutaneous ultrasound-guided radiofrequency ablation (RFA). MATERIALS AND METHODS: Clinical and imaging data from 76 patients (154 lesions) with CLM who underwent percutaneous ultrasound-guided RFA and had KRAS gene test results between January 2012 and June 2016 were analyzed. The average lesion size was 2.3 ± 1.0 cm (range 0.9-5.7 cm); 38 cases (82 lesions) had wild-type KRAS, and 38 cases (72 lesions) had KRAS mutations. RESULTS: The technique effectiveness was 98.1% (151/154), and the LTP rate was 18.2% (28/154) after RFA, which was performed between January 2012 and November 2017. The mean and median follow-up were 32.7 ± 2.5 and 32.0 ± 2.6 months (range 1-70 months), respectively. Cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA for all patients were 7.4, 14.5, 17.8 and 19.2%, respectively. The LTP rate for patients with mutant KRAS (27.8% [20/72]) was significantly higher than that in patients with wild-type KRAS (9.8% [8/82]; p = .004). The cumulative LTP rates at 6 months and 1, 2 and 3 years post-RFA were 4.0, 11.1, 11.1 and 11.1%, respectively, for patients with wild-type KRAS and 11.2, 18.4, 25.2 and 36.2%, respectively, for patient with mutant KRAS (p = .011). Univariate (p = .011) and multivariate analyses (p = .005) showed that KRAS genotype in liver metastases was predictive of LTP. Multivariate analysis also showed that ablation margin size (p< .001) and modified clinical risk score (CRS; p = .033) were independent prognostic factors for LTP. CONCLUSIONS: KRAS gene status of liver metastatic lesions was associated with LTP rates after RFA of CLM. Ablation margin size and modified CRS were also independent prognostic factors for LTP.

Long-term outcomes and prognostic analysis of percutaneous radiofrequency ablation in liver metastasis from breast cancer.

OBJECTIVE: To evaluate the long-term efficacy and prognostic factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) for breast cancer liver metastasis (BCLM). METHODS: Between 2000 and 2015, 69 patients who underwent ultrasound-guided percutaneous RFA for BCLM and had regular follow-up examinations were included. All patients had undergone resection of the primary breast cancer and had received chemotherapy, endocrine therapy or both after surgery. The sample included two males and 67 females with an average age of 50.3 ± 10.0 years (31-76 y). The mean maximum diameter of metastatic lesions in the liver was 2.9 ± 1.4 cm (1.0-6 cm). Thirty-five patients had a single metastasis, while 34 patients had multiple liver metastases (2-5 lesions). Survival results were generated using Kaplan-Meier estimates and a multivariate analysis was performed using the Cox regression model. RESULTS: In total, 92 RFA sessions were performed and 135 BCLM lesions were treated. Major complications occurred in one of the 92 sessions (1.1%). Technical efficacy was achieved in 92.6% of lesions (125/135 lesions). Local tumor progression occurred in 11.6% (8/69) of patients and new intrahepatic metastasis occurred in 55.1% (38/69) of patients. From the time of initial RFA, the median overall survival was 26 months, and the one-, two-, three- and five -year survival rates were 81.8, 50.1, 25.3 and 11.0%, respectively. Based on the multivariate analysis, the following three factors were identified as independent prognostic factors for overall survival: tumor size (p = .017), positive estrogen receptor status (p = .009) and extrahepatic metastatic disease (p = .001). The median progression-free survival was 24 months, and the one-, two-, three- and five -year survival rates after RFA were 77.4, 47.0, 23.7 and 8.5%, respectively. Additionally, the independent prognostic factors for progression-free survival included tumor size (p = .011), ER positivity (p = .001), margin size (p = .017) and extrahepatic metastatic disease (p < .001). CONCLUSION: The results of this study showed that RFA is a safe and locally effective method for the treatment of BCLM, especially in patients with lesions measuring less than 3 cm in diameter, a single liver metastasis, positive estrogen receptor status and no extrahepatic metastases. Also, patients with margin size >10 mm had no local tumor progression.