Multi-field-driven optomechanical entanglement.

Cavity optomechanical (COM) entanglement, playing an essential role in building quantum networks and enhancing quantum sensors, is usually weak and easily destroyed by noises. As feasible and effective ways to overcome this obstacle, optical or mechanical parametric modulations have been used to improve the quality of quantum squeezing or entanglement in various COM systems. However, the possibility of combining these powerful means to enhance COM entanglement has yet to be explored. Here, we fill this gap by studying a COM system containing an intra-cavity optical parametric amplifier (OPA), driven optically and mechanically. By tuning the relative strength and the frequency mismatch of optical and mechanical driving fields, we find that constructive interference can emerge and significantly improve the strength of COM entanglement and its robustness to thermal noises. This work sheds what we believe to be a new light on preparing and protecting quantum states with multi-field driven COM systems for diverse applications.

Factors associated with dysmenorrhoea and menorrhagia improvement in patients with adenomyosis after uterine artery embolisation.

BACKGROUND: This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation (UAE) in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. METHODS: This retrospective study included women with adenomyosis who underwent bilateral UAE between December 2014 and December 2016. The percentage of the volume of the absence of contrast enhancement on T1-weighted images was evaluated 5-7 days after UAE. A receiver operating characteristic (ROC) analysis was used to determine a cut-off point and predict the improvement of dysmenorrhoea and menorrhagia. RESULTS: Forty-eight patients were included. At 24 and 36 months after UAE, the improvement rates for dysmenorrhoea and menorrhagia were 60.4% (29/48) and 85.7% (30/35), and the recurrence rates were 19.4% (7/36) and 9.1% (3/33), respectively. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with the improvement of dysmenorrhoea (p = 0.001, OR = 1.051; 95% CI: 1.02-1.08) and menorrhagia (p = 0.006, OR = 1.077; 95% CI: 1.021-1.136). When the cut-off value of the ROC analysis was 73.1%, sensitivity, specificity, positive predictive value, and negative predictive value for the improvement of dysmenorrhoea were 58.6%, 94.7%, 94.4%, and 60%, while they were 58.9%, 80%, 100%, 100%, and 45.5% for the improvement of dysmenorrhoea. CONCLUSION: Bilateral UAE for symptomatic adenomyosis led to good improvement of dysmenorrhoea and menorrhagia. The percentage of the volume of the absence of contrast enhancement on T1-weighted images of the uterus in postoperative magnetic resonance imaging might be associated with the improvement of dysmenorrhoea and menorrhagia.

This study examined the improvement of dysmenorrhoea and menorrhagia after uterine artery embolisation in women with symptomatic adenomyosis and identified factors that could predict the improvement of dysmenorrhoea and menorrhagia. This retrospective study included women with adenomyosis who underwent uterine artery embolisation. A total of 48 patients were included. Only the percentage of the volume of the absence of contrast enhancement on T1-weighted images was associated with improvement of dysmenorrhoea and menorrhagia. Bilateral uterine artery embolisation for symptomatic adenomyosis led to good improvement. The percentage of the volume of the absence of contrast enhancement on images in postoperative T1-weighted magnetic resonance imaging of the uterus might be associated with the improvement of dysmenorrhoea and menorrhagia.

Efficient Underground Tunnel Place Recognition Algorithm Based on Farthest Point Subsampling and Dual-Attention Transformer.

An autonomous place recognition system is essential for scenarios where GPS is useless, such as underground tunnels. However, it is difficult to use existing algorithms to fully utilize the small number of effective features in underground tunnel data, and recognition accuracy is difficult to guarantee. In order to solve this challenge, an efficient point cloud position recognition algorithm, named Dual-Attention Transformer Network (DAT-Net), is proposed in this paper. The algorithm firstly adopts the farthest point downsampling module to eliminate the invalid redundant points in the point cloud data and retain the basic shape of the point cloud, which reduces the size of the point cloud and, at the same time, reduces the influence of the invalid point cloud on the data analysis. After that, this paper proposes the dual-attention Transformer module to facilitate local information exchange by utilizing the multi-head self-attention mechanism. It extracts local descriptors and integrates highly discriminative global descriptors based on global context with the help of a feature fusion layer to obtain a more accurate and robust global feature representation. Experimental results show that the method proposed in this paper achieves an average F1 score of 0.841 on the SubT-Tunnel dataset and outperforms many existing state-of-the-art algorithms in recognition accuracy and robustness tests.

Transradial versus Transfemoral Access for Patients with Liver Cancer Undergoing Hepatic Arterial Infusion Chemotherapy: Patient Experience and Procedural Complications.

PURPOSE: To determine whether transradial access (TRA) is a more favorable and safe method for hepatic arterial infusion chemotherapy (HAIC) than transfemoral access (TFA). MATERIALS AND METHODS: Retrospective and prospective cohorts of patients with liver cancer were included. Sixty-seven patients in the retrospective cohort were divided into 2 groups: (a) TRA-HAIC (n = 24) and (b) TFA-HAIC (n = 43). Another 33 patients were prospectively enrolled to receive both TRA and TFA for HAIC in a crossover design. Prolonged arterial access was required for up to 48 hours. The primary endpoint was quality of life (QOL) using the visual analog scale. The secondary endpoints mainly included procedural success, adverse events, and operation time. RESULTS: Patient QOL measures revealed significantly lower scores of indices in the TRA-HAIC group than in the TFA-HAIC group in the retrospective cohort (all P < .001). The significant improvement of the QOL indices by TRA-HAIC, such as overall discomfort (P = .019) and pain at the access site (P = .018), was validated in the prospective cohort. The satisfaction scores were significantly higher in the TRA-HAIC group than in the TFA-HAIC group, and patients preferred TRA-HAIC (P < .001). Radial artery occlusion (RAO) as an access-related adverse event occurred more frequently in both the retrospective and prospective cohorts (38% and 33%, P < .001 and P = .001, respectively). Notably, the multivariate analysis of RAO-associated factors showed that enoxaparin use was significantly correlated with a reduced risk of postprocedural RAO (P = .036). CONCLUSIONS: TRA was superior to TFA in patient experience. However, because of the high incidence of access-related adverse events, especially for RAO with a total incidence of 35%, strategies should be optimized for patients to benefit from TRA in future procedures.

Computational fluid dynamics simulation of hemodynamic changes in a hemodialysis patient with central venous stenosis treated with stent.

BACKGROUND: It has not been demonstrated that computational fluid dynamics (CFD) can be used to model central venous stenosis (CVS), nor that hemodynamic changes in CVS treated with stent placement can be anticipated. The purpose of this study was to demonstrate the hemodynamic performance of CVS patients treated with stent placement. METHODS: Patient-specific geometric models were constructed using computed tomography images of veins from hemodialysis patients treated with stent placement. CFD simulation based on geometry was performed using ANSYS-15 to compare pressure quantitatively, wall shear stress (WSS), and flow velocity in the brachial vein before and after stent placement. RESULTS: Following a covered stent placement, the swelling of the left upper extremity was relieved. Prior to stent implantation, the maximum and mean brachial vein wall pressures were 465.2 Pa and 224.609 Pa, respectively. It was determined that the maximum WSS value was 8.449 Pa and that the mean WSS value was 0.743 Pa. The maximum and mean flow velocities were 1.16 and 0.173 m/s, respectively. After stent placement, the maximum wall pressure, maximum WSS, and maximum flow velocity dropped by 59.4%, 71.2%, and 57.8%, respectively. The mean wall pressure, mean WSS, and mean flow rate decreased by 43.5%, 52.7%, and 17.6%, respectively. CONCLUSION: Hemodynamics of CVS in hemodialysis patients exhibited turbulent, imbalances and disorders, which can be improved by stent placement.

Inhibition of matrix stiffness relating integrin ß1 signaling pathway inhibits tumor growth in vitro and in hepatocellular cancer xenografts.

BACKGROUND: Cancer development is strictly correlated to composition and physical properties of the extracellular matrix. Particularly, a higher matrix stiffness has been demonstrated to promote tumor sustained growth. Our purpose was to explore the role of matrix stiffness in liver cancer development. METHODS: The matrix stiffness of tumor tissues was determined by atomic force microscopy (AFM) analysis. In vitro, we used a tunable Polyacrylamide (PA) hydrogels culture system for liver cancer cells culture. The expression level of integrin ß1, phosphorylated FAK, ERK1/2, and NF-κB in SMMC-7721 cells was measured by western blotting analysis. We performed MTT, colony formation and transwell assay to examine the tumorigenic and metastatic potential of SMMC-7721 cells cultured on the tunable PA hydrogels. SMMC-7721 cancer xenografts were established to explore the anticancer effects of integrin inhibitors. RESULTS: Our study provided evidence that liver tumor tissues from metastatic patients possessed a higher matrix stiffness, when compared to the non-metastatic group. Liver cancer cells cultured on high stiffness PA hydrogels displayed enhanced tumorigenic potential and migrative properties. Mechanistically, activation of integrin ß1/FAK/ ERK1/2/NF-κB signaling pathway was observed in SMMC-7721 cells cultured on high stiffness PA hydrogels. Inhibition of ERK1/2, FAK, and NF-κB signaling suppressed the pro-tumor effects induced by matrix stiffness. Combination of chemotherapy and integrin ß1 inhibitor suppressed the tumor growth and prolonged survival time in hepatocellular cancer xenografts. CONCLUSION: A higher matrix stiffness equipped tumor cells with enhanced stemness and proliferative characteristics, which was dependent on the activation of integrin ß1/FAK/ERK1/2/NF-κB signaling pathway. Blockade of integrin signals efficiently improved the outcome of chemotherapy, which described an innovative approach for liver cancer treatment.

Optomechanical transistor: controlling the optical bistability in a photonic molecule.

We theoretically investigate the optical bistability in a composite photonic molecule cavity optomechanical system consisting of two whispering gallery mode microcavities, where one of the optical cavities is optomechanical with a high quality factor, and the other optical cavity is an auxiliary cavity with high cavity dissipation. By controlling the coupling strength J between the two cavities determined by their distance, the decay rate ratio δ of the two cavities, and the pump power P, the optical bistability can be controlled. Further, the transmission spectrum of the signal field can be efficiently attenuated or amplified, depending on the power of a second "gating" (pump) field P, and other parameters. Our study for photonic-molecule optomechanics systems may be a promising candidate for single-photon transistors and pave the way for potential applications in quantum information technologies.

Constructing an experiential education model in undergraduate radiology education by the utilization of the picture archiving and communication system (PACS).

BACKGROUND: Medical education in China is in a transitional period, from passive learning models to experiential education. We modified an experiential education method for radiology education. The aim of this study is to evaluate the effect of this method on undergraduate radiology education. METHOD: With the help of the picture archiving and communication system (PACS) and RadiAnt DICOM Viewer, we modified an experiential education method that simulates similar working conditions for undergraduate medical students to formulate radiology diagnosis similar to clinical radiologists. A total of 101 students were allocated into either the experiential education group or the control group. The final examination scores and a 5-point Likert scale self-assessment questionnaire of radiologic skills were collected from all the students as an objective assessment and a subjective assessment respectively. A questionnaire was also used to assess the satisfaction with the experiential model in the experiential education group. Mann-Whitney U test was used to compare the ranked data, and t-tests were used to compare the numeric data. RESULTS: The experiential education group demonstrated significantly higher scores (7.4 ± 1.3) compared to the control group (6.7 ± 1.5, p < 0.05) in the question type "description and diagnosis". The self-assessment questionnaire indicated that the experiential education was related to increased familiarity with the diagnosis thinking principle and the sequences and reconstruction methods of computer tomography (CT) imaging, which also strengthen participants' self-confidence to perform future clinical work (p < 0.05). The self-assessment questionnaire in the experiential education group showed that the majority of students were satisfied with the organization (82.5%), interactivity (85%) and quality (85%) of the learning activity. Most students found this model of learning to be helpful for studying radiology (85%) and for understanding anatomy (90%). CONCLUSION: Compared with the traditional radiology education approach, the experiential education method showed greater efficacy in improving students' analysis and diagnostic skills and their self-confidence.

Is Emergency Transcatheter Hepatic Arterial Embolization Suitable for Spontaneously Ruptured Hepatocellular Carcinoma in Child-Pugh C Cirrhosis?

PURPOSE: To evaluate the utility of emergent transcatheter arterial embolization for spontaneously ruptured hepatocellular carcinoma (HCC) in patients with Child-Pugh class C (CPC) liver cirrhosis presenting hemorrhagic shock. MATERIALS AND METHODS: A study of all 94 patients was retrospectively conducted from January 2006 to January 2016. Sixty patients underwent conservative treatment (control group) and 34 underwent embolization. RESULTS: Embolization provided better stabilization of hemodynamic status than conservative treatment (91.2% vs 61.7%), with greater overall survival (OS) rates at 30, 60, and 120 days (73.5%, 52.9%, and 29.4% vs 33.3%, 13.3%, and 0%, respectively). Mean follow-up duration was 51.07 days (range, 3-237 d). Median survival time was longer for the embolization group than the control group, specifically for patients with a shock index (SI) of ≥ 0.6 to < 1 (106.0 d ± 39.4 vs 34.0 d ± 4.7) or ≥ 1 (18.0 d ± 7.5 vs 11.0 d ± 3.2), those with CPC scores 10 or 11 (88.0 d ± 29.4 vs 28.0 d ± 4.5), and those with segmental (165.0 d ± 20.6 vs 34.0 d ± 9.7) or lobar (54.0 d ± 7.9 vs 26.0 d ± 3.4) portal vein tumor thrombus (PVTT). SI ≥ 1, Child-Pugh score of 12/13, tumor size ≥ 10 cm, and PVTT were independent factors in poor prognosis for OS. CONCLUSIONS: Emergent transcatheter arterial embolization is an effective intervention for ruptured HCC in patients with CPC liver function in hemorrhagic shock, particularly those with a SI ≥ 1, Child-Pugh scores of 10/11, and first- or lower-order PVTT.

Design, synthesis and structure-activity relationship studies of novel free fatty acid receptor 1 agonists bearing amide linker.

The free fatty acid receptor 1 (FFA1/GPR40) has attracted extensive attention as a novel antidiabetic target. Aiming to explore the chemical space of FFA1 agonists, a new series of lead compounds with amide linker were designed and synthesized by combining the scaffolds of NIH screened lead compound 1 and GW9508. Among them, the optimal lead compound 17 exhibited a considerable agonistic activity (45.78%) compared to the NIH screened compound 1 (15.32%). During OGTT in normal mice, the compound 17 revealed a significant glucose-lowering effect (-23.7%) at the dose of 50mg/kg, proximity to the hypoglycemic effect (-27.8%) of Metformin (200mg/kg). In addition, the compound 17 (100mg/kg) also exhibited a significant improvement in glucose tolerance with a 29.1% reduction of glucose AUC0-2h in type 2 diabetic mice. All of these results indicated that compound 17 was considered to be a promising lead structure suitable for further optimization.

Overall survival in response to sorafenib with transarterial chemoembolization for BCLC stage B hepatocellular carcinoma: propensity score analysis
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OBJECTIVE: Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) is a heterogeneous disease group. Transarterial chemoembolization (TACE) is indicated for BCLC stage B HCC, while sorafenib is indicated for BCLC stage C HCC. This study aimed to evaluate the efficacy of TACE+sorafenib compared with TACE monotherapy in the treatment of BCLC stage B HCC. MATERIALS: Patients with BCLC stage B unresectable HCC. METHODS: This was a retrospective study in patients with BCLC stage B HCC who received TACE (n = 144) or TACE+sorafenib (n = 46) between January 2008 and January 2014. Child-Pugh classification, history of hepatitis or cirrhosis, nodule number, tumor vascularity, ECOG performance status, adverse events, and survival were evaluated. Patients were matched 1 : 1 using the propensity score approach. RESULTS: Median overall survival (OS) was 18.0 months in the TACE+sorafenib group compared with 10.0 months for TACE (p = 0.002). In matched patients, multivariate analysis showed that the use of TACE+sorafenib (HR = 0.351, 95%CI: 0.215-0.574, p < 0.001) and multiple-diffuse nodules (HR = 0.497, 95% CI: 0.293 - 0.884, p = 0.010) were independently associated with a better prognosis. Subgroup analysis showed survival benefits for patients with Child-Pugh A classification (p = 0.001), cirrhosis (p = 0.001), hepatitis B (p < 0.001), hypovascular lesion (p = 0.001), and both single/multiple nodules p = 0.001). Cumulative rates of adverse events were similar between the two groups (p = 0.155), but hand-foot syndrome (58.7% vs. 12.5%, p < 0.001) and diarrhea (60.9% vs. 40.3%, p = 0.02) were more frequent in the TACE+sorafenib group. CONCLUSIONS: The combination of TACE+sorafenib might improve the OS of patients with BCLC stage B HCC. These results also suggest that some subsets of patients could benefit more from the TACE+sorafenib combination.
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Is Salvage Liver Resection Necessary for Initially Unresectable Hepatocellular Carcinoma Patients Downstaged by Transarterial Chemoembolization? Ten Years of Experience.

INTRODUCTION: This study evaluated long-term outcomes of salvage surgery as additional therapy following downstaging of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) in patients with initially unresectable HCC. METHODS: A retrospective analysis was performed of 831 consecutive patients with unresectable HCC who underwent TACE as initial treatment between June 2004 and December 2014. Of these, 82 patients with downstaged resectable HCC were enrolled in this study: 43 received salvage surgery (S group) and the remaining 39, who refused salvage resection, were the control group (T group). The primary endpoint was overall survival (OS). RESULTS: The median OS in the S and T groups was 49 and 31 months, respectively (p = .027). The 2-, 4-, and 5-year survival rates were 93%, 47%, and 26% in the S group and 74%, 18%, and 10% in the T group, respectively (p = .019). Treatment modality (hazard ratio [HR], 0.337; 95% confidential interval [CI], 0.184-0.616; p < .001) and response to TACE (complete vs. partial; HR, 3.154; 95% CI, 1.709-5.822; p < .001) were independent prognostic factors for survival. The median OS for patients in the complete response and partial response (PR) subgroups was 50 and 49 months, respectively, in the S group and 54 and 24 months, respectively, in the T group (p = .699 and p < .001, respectively). The median OS for HCC patients with macroscopic vascular invasion (MVI) was 58 and 30 months in the S and T groups, respectively (p = .024). CONCLUSION: Salvage surgery after downstaging of unresectable HCC had a survival benefit only for patients with MVI or a PR to TACE. IMPLICATIONS FOR PRACTICE: The results of this study suggest that salvage liver resection after downstaging of unresectable hepatocellular carcinoma in patients with a complete response to transarterial chemoembolization (TACE) has a comparable long-term outcome in this good-prognosis group. Salvage liver resection may provide a better long-term outcome compared with TACE alone, but only in patients with macroscopic vascular invasion or those with a partial response to TACE.

C14orf166 overexpression correlates with tumor progression and poor prognosis of breast cancer.

BACKGROUND: Chromosome 14 open reading frame 166 (C14orf166) is upregulated in various tumors, but its role in breast cancer has not been reported. METHODS: Quantitative real-time PCR and western blot were used to determine C14orf166 expression in normal breast epithelial cells (NBEC), breast cancer cells, and four matched pairs of breast cancer tissues and adjacent noncancerous tissues. Using immunohistochemistry, we determined C14orf166 expression in paraffin-embedded tissues from 121 breast cancer patients. Statistical analyses were performed to examine the associations among C14or166 expression, clinicopathological parameters and prognosis outcome of breast cancer. MTT and colony formation assay were used to determine the effect of C14orf166 on cell proliferation by overexpression or knockdown of C14orf166 level. RESULTS: C14orf166 was upregulated in breast cancer cell lines and tissues compared with the normal cells and adjacent normal breast tissues, high C14orf166 expression was positively with advancing clinical stage. The correlation analysis between C14orf166 expression and clinicopathological characteristics suggested C14orf166 expression was significantly correlated with clinical stages, T classification, N classification and PR expression, Kaplan-Meier curves with log rank tests showed patients with low C14orf166 expression had better survival, Cox-regression analysis suggested C14orf166 was an unfavorable prognostic factor for breast cancer patients. C14orf166 overexpression promoted breast cancer cell proliferation, whereas knockdown of C14orf166 inhibited this effect. Further analysis found C14orf166 overexpression inhibited cell cycle inhibitors P21 and P27 expression, and increased the levels of Cyclin D1 and phosphorylation of Rb, suggesting C14orf166 contributed to cell proliferation by regulating G1/S transition. CONCLUSION: Our findings suggested C14orf166 could be a novel prognostic biomarker of breast cancer, it also contributes to cell proliferation by regulating G1/S transition.

Initial Experience: Alleviation of Pain with Percutaneous CT-Guided Cryoablation for Recurrent Retroperitoneal Soft-Tissue Sarcoma.

PURPOSE: To evaluate the pain-alleviating effect of computed tomography (CT)-guided percutaneous cryoablation for recurrent retroperitoneal soft-tissue sarcomas (RPSs). MATERIALS AND METHODS: Data from 19 men and 20 women (median age, 50.3 y) with recurrent malignant RPS who underwent percutaneous cryoablation were reviewed retrospectively. A total of 50 tumors were treated by cryoablation, including a single tumor in 29 patients, 2 tumors in 9, and 3 tumors in 1. Adverse events and analgesic outcomes were compared as a function of tumor size (< 10 cm and ≥ 10 cm). Efficacy was assessed based on modified Response Evaluation Criteria In Solid Tumors and progression-free survival (PFS). RESULTS: Grade 1/2 adverse events included fever (n = 17), emesis (n = 7), frostbite (n = 5), and local pain (n = 4). The median follow-up period and PFS were 18.5 months (range, 12-42 mo) and 13.4 months ± 6.2, respectively. At the end of follow-up, 13 patients had died and 26 were living. The mean severe local pain scores on pretreatment day 1 and posttreatment days 1, 5, 10, 15, 20, and 25 were 7.49, 7.40, 6.51, 5.81, 5.35, 5.04, and 5.44, respectively, and significant differences versus pretreatment (P < .001) were reported for posttreatment days 5-25. Immediate relief occurred more frequently in the small-tumor group (4 of 7; 57.1%; P = .018), whereas delayed relief occurred more frequently in the large-tumor group (17 of 22; 77.3%; P = .030). CONCLUSIONS: Minimally invasive percutaneous cryoablation improves local pain and is a feasible treatment for recurrent RPSs.

Discovery of novel free fatty acid receptor 1 agonists bearing triazole core via click chemistry.

The free fatty acid receptor 1 (FFA1/GPR40) is a novel antidiabetic target based on particular mechanism in enhancing glucose-stimulated insulin secretion. Most of reported FFA1 agonists, however, have been suffered from relatively high lipophilicity and molecular weight. Aiming to develop potent agonists with improved physicochemical property, 25 compounds containing triazole scaffold and various carboxylic acid fragments were synthesized via the click chemistry. Among them, the optimal lead compound 26 with relatively low lipophicity (LogD7.4=1.95) and molecular weight (Mw = 391.78) exhibited a considerable FFA1 agonistic activity (36.15%). In addition, compound 26 revealed a significant improvement in the glucose tolerance with a 21.4% and 14.2% reduction of glucose AUC0-2h in normal ICR mice and type 2 diabetic C57BL/6 mice, respectively. All of these results demonstrated that compound 26 was considered to be a promising lead compound suitable for further optimization.

The feasibility and safety of a through-and-through wire technique for central venous occlusion in dialysis patients.

BACKGROUND: To retrospectively compare the operation time, success rate and efficacy between unidirectional and bidirectional procedures in the treatment of central venous occlusion diseases (CVOD), assess the advantages of the bidirectional approach, and determine the characteristics of CVOD appropriate for the bidirectional approach treatment. METHODS: A total of 49 patients who underwent endovascular interventions with all relevant data between January 2011 and December 2015 at the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, were included in this retrospective study, and were categorized into two groups: the 19 patients in group 1 had undergone percutaneous transluminal venoplasty (PTV) via a conventional technique (unidirectional procedure from the vein distal or proximal to the obstructive lesion), and the 30 in group 2 had undergone flossing wire technique (bidirectional procedure from femoral vein and the vein distal to obstructive lesion and using a flossing wire technique). The technical success rate, the fluoroscopy time in the procedure, perioperative complications, and patency were evaluated retrospectively. RESULTS: Compared with group 1, group 2 had a higher initial technical success rate (83.33% vs. 47.36%, p = 0.012) but a shorter fluoroscopy time (82.6 ± 26.1 vs. 116.1 ± 42.1, p = 0.048). Receiver operating characteristic (ROC) analysis indicated that a lesion with a length of 6.5 cm was the best predictor of technique success (p = 0.02) in group 1, but no cut-off value was identified for group 2. There were no significant differences in perioperative complications between these two groups. The complication rates were 31.58% (6/19) in group 1 and 6.67% (2/30) in group 2, (p = 0.043), respectively. No significant difference was observed between these two groups with respect to the stent patency rate. CONCLUSION: Compared with the conventional technique, the flossing wire technique has a higher success rate, shorter fluoroscopy time, fewer complications and similar patency rate. It is a feasible treatment for CVOD, especially for long obstructive lesions.

Sorafenib With and Without Transarterial Chemoembolization for Advanced Hepatocellular Carcinoma With Main Portal Vein Tumor Thrombosis: A Retrospective Analysis.

BACKGROUND: The survival benefit of combining sorafenib and transarterial chemoembolization (TACE) therapy compared with sorafenib monotherapy for patients with advanced hepatocellular carcinoma (HCC) and main portal vein tumor thrombosis (MPVTT) is unclear. METHODS: Between January 2009 and June 2013, 183 consecutive patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) and MPVTT were retrospectively reviewed. Of these, 89 patients with advanced HCC and MPVTT were enrolled in this study: 45 were treated with combination therapy (sorafenib-TACE group), and the other 44 treated with sorafenib monotherapy (sorafenib group). RESULTS: The mean number of TACE sessions per patient was 2.6 (range: 1-5). The median duration of sorafenib in the sorafenib-TACE group and sorafenib group was 5.6 months and 5.4 months, respectively. The disease control rate was similar between the two groups. Median time to progression was 3.0 months (95% confidence interval [CI]: 2.2, 3.7) in the sorafenib-TACE group, and 3.0 months (95% CI: 2.1, 3.8) in the sorafenib group (p = .924). Median overall survival was 7.0 months (95% CI: 6.1, 7.8) and 6.0 months (95% CI: 4.7, 7.3) in the sorafenib-TACE group and the sorafenib group, respectively (p = .544). The adverse events related to sorafenib were comparable between the two groups. Twenty-one adverse events of grade 3-4 related to TACE occurred in 12 patients (26.7%), and 2 of them died (4.4%). CONCLUSION: This study demonstrated no advantage of combination therapy over sorafenib monotherapy. Considering the patients' morbidity after TACE, sorafenib monotherapy is appropriate for managing patients with advanced HCC and MPVTT.

URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway.

BACKGROUND: Angiogenesis is essential for tumor growth. Hepatocellular carcinoma (HCC) is characterized by hypervascularity; high levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in HCC. Up-regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP), is overexpressed in multiple tumor types and has been suggested to act as an oncogene. This study aimed to elucidate the effect of URG4/URGCP on the angiogenic capacity of HCC cells in vitro. METHODS: Expression of URG4/URGCP in HCC cell lines and normal liver epithelial cell lines was examined by Western blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or transiently knocked down using a shRNA in two HCC cell lines. The human umbilical vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells. A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa - light - chain - enhancer of activated B cells (NF-κB). NF-κB was inhibited by overexpressing degradation-resistant mutant inhibitor of κB (IκB)-α. Expression of vascular endothelial growth factor C (VEGFC), tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA. RESULTS: URG4/URGCP protein and mRNA expression were significantly upregulated in HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule formation and migration and neovascularization in the CAM assay. Furthermore, overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased - VEGFC expression, NF-κB transcriptional activity, the levels of phosphorylated (but not total) IκB kinase (IKK) and IκB-α, and expression of TNFα, IL-6, IL-8 and MYC in HCC cells. Additionally, inhibition of NF-κB activity in HCC cells abrogated URG4/URGCP-induced NF-κB activation and angiogenic capacity. CONCLUSIONS: This study suggests that URG4/URGCP plays an important pro-angiogenic role in HCC via a mechanism linked to activation of the NF-κB pathway; URG4/URGCP may represent a potential target for anti-angiogenic therapy in HCC.

Design, synthesis and structure-activity relationship studies of novel phenoxyacetamide-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes.

The free fatty acid receptor 1 (FFA1) has attracted extensive attention as a novel antidiabetic target in the last decade. Several FFA1 agonists reported in the literature have been suffered from relatively high molecular weight and lipophilicity. We have previously reported the FFA1 agonist 1. Based on the common amide structural characteristic of SAR1 and NIH screened compound, we here describe the continued structure-activity exploration to decrease the molecular weight and lipophilicity of the compound 1 series by converting various amide linkers. All of these efforts lead to the discovery of the preferable lead compound 18, a compound with considerable agonistic activity, high LE and LLE values, lower lipophilicity than previously reported agonists, and appreciable efficacy on glucose tolerance in both normal and type 2 diabetic mice.

Design, synthesis and biological activity of phenoxyacetic acid derivatives as novel free fatty acid receptor 1 agonists.

The free fatty acid receptor 1 (FFA1) is a novel antidiabetic target for the treatment of type 2 diabetes based on particular mechanism in amplifying glucose-stimulated insulin secretion. We have previously identified a series of phenoxyacetic acid derivatives. Herein, we describe the further chemical modification of this series directed by ligand efficiency and ligand lipophilicity efficiency. All of these efforts lead to the discovery of the promising candidate 16, an excellent FFA1 agonist with robust agonistic activity (43.6 nM), desired LE and LLE values. Moreover, compound 16 revealed a great potential for improving the hyperglycemia levels in both normal and type 2 diabetic mice without the risk of hypoglycemia even at the high dose of 40 mg/kg.