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Magnesium phosphate cement (MPC) has been applied in grouting engineering due to its features of quick setting, high early-strength, and perfect volume stability. The rheological properties (RPs) of MPC, being vitally important for site operation, need to be studied further. Sodium tripolyphosphate (STP) is one type of high-efficiency retarders used in MPC. This study investigated the effects of STP content on the RPs of MPC pastes, and the mechanisms were studied by characterizing the zeta potential, 1H NMR relaxation signal, water film thickness, mineral changes, and electrical impedance. Experimental results indicate that the plastic viscosity (η) increases gradually and the yield stress (τ0) decreases firstly and then increases with increasing the STP content. The influencing mechanisms of STP need to be distinguished by analyzing η and τ0 respectively. The water film thickness and the amount of intermediate hydration products within 15 min of hydration is directly related to the change in η. The porosity and distribution of free water obtained from 1H NMR in MPC slurry are the dominant factor for τ0, and followed by the diffused double layer. It is noteworthy that zeta potential is not an effective measure for studying the RPs of MPC. Results of electrical impedance also explain the mechanisms of STP retarding the hydration and improving the early-term strength of MPC.

BACKGROUND Transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) can improve the survival of patients with hepatocellular carcinoma (HCC). The purpose was to explore the characteristics of high-risk and low-risk groups of HCC patients receiving combination therapy using a decision tree model. MATERIAL AND METHODS This retrospective cohort study investigated HCC patients treated with a combination of TACE and RFA at our hospital from 2012 to 2018. Decision tree analysis was used to study the 1-year prognosis of patients, and patients were divided into high-risk and low-risk groups. RESULTS We included a total of 142 patients with HCC, 21.83% female and 78.17% male, with the median age of 60 years old. The median follow-up was 13.5 months; 39.44% of patients had progressive disease or death (high-risk group) and 60.56% of patients did not have progressive disease or survival (low-risk group). The area under the curve (AUC) of the decision tree model was 0.846. There were significant differences in sex (P=0.003), age (P=0.038), tumor number (P=0.043), number of RFAs in the first treatment cycle (P.

Background and aims Optimal candidates for early transjugular intrahepatic portosystemic shunt (TIPS) in patients with Child-Pugh B cirrhosis and acute variceal bleeding (AVB) remain unclear. This study aimed to test the hypothesis that risk stratification using the Chronic Liver Failure Consortium Acute Decompensation score (CLIF-C ADs) may be useful to identify a subgroup at high risk of mortality or further bleeding that may benefit from early TIPS in patients with Child-Pugh B cirrhosis and AVB. Approach and results We analyzed the pooled individual data from two previous studies of 608 patients with Child-Pugh B cirrhosis and AVB who received standard treatment between 2010 and 2017 in China. The concordance index values of CLIF-C ADs for 6-week and 1-year mortality (0.715 and 0.708) were significantly better than those of active bleeding at endoscopy (0.633 [P 56), with a 5.6%, 16.8%, and 25.4% risk of 6-week death, respectively. Nevertheless, the performance of CLIF-C ADs for predicting a composite endpoint of 6-week death or further bleeding was not satisfactory (area under the receiver operating characteristics curve [AUC], 0.588). A nomogram incorporating components of CLIF-C ADs and albumin, platelet, active bleeding, and ascites significantly improved the prediction accuracy (AUC, 0.725). Conclusions In patients with Child-Pugh B cirrhosis and AVB, risk stratification using CLIF-C ADs identifies a subgroup with high risk of death that may derive survival benefit from early TIPS. With improved prediction accuracy for 6-week death or further bleeding, the data-driven nomogram may help to stratify patients in randomized trials. Future external validation of these findings in patients with different etiologies is required.

The development of magnesium oxychloride cement can effectively utilize the waste of potash industry and reduce its harm to the environment. Although magnesium oxychloride cement paste (MOCP) has excellent performance in dry environment, its performance is greatly deteriorated in water or humid environment, which severely limits its practical application. In order to improve the water resistance of MOCP, MOCP was modified by various gypsum in this study, and the intrinsic mechanism was explored. Results showed that replacing MgO with gypsum delayed the setting time of MOCP and effectively improved its volume stability. Although the incorporation of gypsum reduced the 14-d air-cured compressive strength of MOCP, waste gypsum was able to significantly improve the water resistance of MOCP compared to natural gypsum. When 80% flue gas desulfurization gypsum and phosphogypsum (weight of magnesium oxide) were incorporated into MOCP, the 14-d air-cured compressive strength of MOCP was only decreased by 14.49% and 15.94% compared with the control group, but its 28-d water immersion strength retention coefficient (SRC) could still reach 61.02% and 46.55%, respectively. However, for the control group and MOCP with 80% natural gypsum, the 28-d SRC were only 28.99% and 8.41%. The incorporation of high-volume waste gypsum to MOCP not only reduced the relative content of MgO, but also improved the stability of the 5-phase in water, which was beneficial to improve the water resistance of MOCP. In addition, high-volume waste gypsum-modified MOCP had lower cost and carbon emissions, and exhibited superior water resistance and sustainability compared to existing MOCP compositions.

OBJECTIVES Patients with severe cirrhotic ascites have poor prognosis, yet individual patient survival varies greatly. Therefore, suitable prognostic models can be helpful in clinical decision making. The aim of this study was to evaluate and compare the performance of 10 scores in predicting transplant-free survival (TFS) after transjugular intrahepatic portosystemic shunt (TIPS) in severe cirrhotic ascites. METHODS Two hundred eighty consecutive cirrhotic patients with severe ascites undergoing TIPS between March 2006 and December 2017 were retrospectively screened and included from nine tertiary Chinese centers, consisting of 123 patients with refractory ascites and 157 with recurrent ascites. Discriminatory ability of these models was further assessed in the whole cohort and subgroups. RESULTS TFS rates of all 280 patients were 75.4, 65.7, and 53.6% at 6-month, 1-year, and 2-year follow-up, respectively. Compared with other prognostic systems, the integrated model for end-stage liver disease (iMELD, incorporating serum sodium and age) showed optimal performance in predicting 6-month, 1-year, and 2-year TFS. Cutoffs were determined according to c-index and were used to stratify patients into three strata presenting significantly different TFS for short-term and long-term: iMELD

A sand-box experiment equipment is constructed to simulate the transportation of contaminant in unsaturated flow under dirichlet boundary condition. Based on analysis of the mechanism in unsaturated migration, taking a riverland as an example, the model of water quality which was affected by contaminant transport was built, and the calculation values coincided well with experimental data. The results showed that the lateral migration should not be neglected when seepage velocity was high. In addition, the lateral migration was faster in high moisture content areas and the solute was retained for a short time; however, the situation was reversed in low moisture content areas. Moreover, during the initial stage of solute transport, the velocity of the trailing end of the pinnate pollution zone was high under the effect of capillary action, which would lead to expansion of the range of pollution. Furthermore, the relative concentration curve of pollutants presented a single peak state, with the peak value of the curve increasing with the velocity, and the arrival time of the peak value was also gradually advanced. Therefore, this study can provide reference for the prediction and control of groundwater contaminant transport in an unsaturated zone.

Preemptive TIPS Individual Data Metanalysis, International Variceal Bleeding Study and Baveno Cooperation Study groups., [Background & Aims] Compared with drugs plus endoscopy, placement of transjugular portosystemic shunt within 72 hours of admission to the hospital (early or preventive transjugular intrahepatic portosystemic shunt [TIPS], also called preemptive TIPS) increases the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survive for 1 year. However, the benefit of preemptive TIPS is less clear for patients with a Child-Pugh score of B and active bleeding (CP-B+AB). We performed an individual data meta-analysis to assess the efficacy of preemptive TIPS in these patients and identify factors associated with reduced survival of patients receiving preemptive TIPS., [Method] We searched publication databases for randomized controlled trials and observational studies comparing the effects of preemptive TIPS versus endoscopy plus nonselective beta-blockers in the specific population of high-risk patients with cirrhosis and acute variceal bleeding (CP-B+AB or Child-Pugh C, below 14 points), through December 31, 2019. We performed a meta-analysis of data from 7 studies (3 randomized controlled trials and 4 observational studies), comprising 1327 patients (310 received preemptive TIPS and 1017 received drugs plus endoscopy). We built adjusted models to evaluate risk using propensity score for baseline covariates. Multivariate Cox regression models were used to assess the factors associated with survival time. The primary endpoint was effects of preemptive TIPS versus drugs plus endoscopy on 1-year survival in the overall population as well as CP-B+AB and Child-Pugh C patients., [Results] Overall, preemptive TIPS significantly increased the proportion of high-risk patients with cirrhosis and acute variceal bleeding who survived for 1 year, compared with drugs plus endoscopy (hazard ratio [HR] 0.443; 95% CI 0.323–0.607; P < .001). This effect was observed in CP-B+AB patients (HR 0.524; 95% CI 0.307–0.896; P = .018) and in patients with Child-Pugh C scores below 14 points (HR 0.374; 95% CI 0.253–0.553; P < .001). Preemptive TIPS significantly improved control of bleeding and ascites without increasing risk of hepatic encephalopathy in Child-Pugh C and CP-B+AB patients, compared with drugs plus endoscopy. Cox analysis of patients who received preemptive TIPS showed that patients could be classified into 3 categories for risk of death, based on age, serum level of creatinine, and Child-Pugh score. In each of these risk categories, preemptive TIPS increased the proportion of patients who survived for 1 year, compared with drugs plus endoscopy., [Conclusions] In a meta-analysis of data from 1327 patients with cirrhosis, acute variceal bleeding, and Child-Pugh score between 10 and 13 points or CP-B+AB, preemptive TIPS increased the proportion who survived for 1 year, in both subgroups separately, compared with drugs plus endoscopy., Juan Carlos García-Pagán received support in part through grants from the Spanish Ministry of Education and Science (SAF-2016–75767-R and PIE 15/00027) and from the “Commissioner for Universities and Research of the Generalitat de Catalunya” (AGAUR SGR 2017). CIBERehd is funded by the Instituto de Salud Carlos III. Edilmar Alvarado-Tapias and Anna Baiges are recipients of a "Río Hortega" fellowship grant from the Instituto de Salud Carlos III. The study was partially supported by a GORE grant for statistical support.

Background & Aims Placement of an irradiation stent has been demonstrated to offer longer patency and survival than an uncovered self-expandable metallic stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO). We aim to further assess the efficacy of an irradiation stent compared to an uncovered SEMS in those patients. Methods We performed a randomized, open-label trial of participants with unresectable MBO at 20 centers in China. A total of 328 participants were allocated in parallel to the irradiation stent group (ISG) or the uncovered SEMS group (USG). Endpoints included stent patency (primary), technical success, relief of jaundice, overall survival, and complications. Results The first quartile stent patency time (when 25% of the patients experienced stent restenosis) was 212 days for the ISG and 104 days for the USG. Irradiation stents were significantly associated with a decrease in the rate of stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at 360 days; p = 0.010). Patients in the ISG obtained longer survival time (median 202 days vs. 140 days; p = 0.020). No significant results were observed in technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%; p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p = 0.841). Conclusions Insertion of irradiation stents instead of uncovered SEMS could improve patency and overall survival in patients with unresectable MBO. Lay summary For patients with unresectable malignant biliary obstruction (MBO), placement of a self-expandable metallic stent (SEMS) is a recommended palliative modality to relieve pruritus, cholangitis, pain, and jaundice. However, restenosis is a main pitfall after stent placement. Data from this first multicenter randomized controlled trial showed that insertion of an irradiation stent provided longer patency and better survival than a conventional metal stent. ClinicalTrials.gov ID: NCT02001779.

In this work, a harmonic piecewise linearisation-wavelet transform method is proposed for identification of some kind of non-linear/linear vibration “black box” systems. The proposed method firstly looks at the non-linear vibration system as piecewise linear, and then identifies the time-varying damping ratio and frequency by the segmented amplitude log analysis and wavelet transform method, secondly it obtains the relationship between damping and frequency to time or amplitude by least squares method, and finally establishes its non-linear oscillation governing equation. The proposed harmonic piecewise linearisation-wavelet transform method is verified by two numerical examples and then is used to identify the wind-induced cross-wind non-linear/linear aerodynamic parameters of Shanghai’s World Financial Centre by aeroelastic model vibration measurement wind tunnel test. The results show that the proposed harmonic piecewise linearisation-wavelet transform method is feasible for identification of some kind of non-linear/linear “black box” vibration systems, including in a flexible high-rise building subjected to strong wind: in this case, the non-linear/linear aeroelasticity effect cannot be ignored, which would generate additional weak non-linear damping and negative aerodynamic stiffness.

In comparison to other accelerating curing methods in cement-based materials, the direct electric curing (DEC) has unique advantages of easily operating and high-quality controlling. Through employing the fixed voltage and frequency of alternating current, the influence of DEC time ranging from 0 to 24 h on Portland cement was investigated. The optimal DEC time was proposed by measuring the flexural strength, compressive strength , pore structure, capillary water absorption. The influencing mechanism of DEC on the properties of cement was studied by using TGA and XRD analysis. This study also compared the potential CO 2 emission of four methods for preparing high early-strength cement-based materials. The results indicate that short time, i.e., within 2 h, of DEC cannot improve both early-term and middle-term strength. The optimal DEC time is about 6 h, through which the increment in 1-day and 28-day strength, improvement of pore structure and capillary water absorption can be obtained. Superfluous DEC decreases the middle-term strength and makes the pore structure much coarser because delayed ettringite formation (DEF) was observed in 24 h of DEC cured specimens. Judged only by strength requirement, DEC is indeed much cleaner than steam curing, but it has no advantage over the methods of Portland cement with composite early-strength agent or Portland cement with sulphoaluminate cement. While considering CO 2 emission, cost, durability and strength requirement together, DEC is the most effective and environmentally friendly method.

Magnesium phosphate cement (MPC) with unique advantages of quick setting and high early-strength has been used as grouting materials. The rheological properties of MPC, being vitally important for site operation, need to be studied further. Dead burnt magnesia (MgO) and phosphate (ADP) are the main raw materials for preparing MPC. This study measured the rheological properties with different M/P ratios, and the mechanisms of M/P ratio were studied by characterizing the zeta potential, 1H NMR relaxation signal, water film thickness, mineral changes and electrical impedance. Experimental results indicate that both the yield stress (τ0) and plastic viscosity (η) decrease firstly and then increase gradually with increasing the M/P ratio from 2.5:1 to 4.5:1. Higher M/P ratio decreases the interparticle water film thickness and accelerates the initial hydration rate remarkably, which is responsible for the change in rheological parameters. Low field NMR, TG-DTG analysis and Nyquist plots confirm the quicker initial hydration in MPC with higher M/P ratio. The change in hydration products is very slight during the rheological property measurements. Nyquist plots show that the MPC paste with lower M/P ratios has more compact microstructure and lower porosity at several hours. In a word, initial hydration rate is the most important factor influencing the rheological properties of MPC, and the separation distance among solid particles is the secondary factor.

Magnesium phosphate cement (MPC), as a new-fashioned cementitious material with doubly consensus superiorities of rapid-setting and ultra-high early strength, has a significant utilization potentiality in multi-extremely complicated engineering fields. Borax had been employed for prolonging the setting time of MPC as an unexceptionable retarder, which has been verified and approved practically. Nevertheless, the effect of early-hydration behavior on rheological properties (RPs) in borax-admixed MPC remains obscure. Consequently, we adopted rheometer to investigate the RPs of MPC with different borax contents, and then discussed the relationship between yield stress and plastic viscosity affected by hydration process. In addition, a series of microscopic methods were utilized for further exploring the influence of hydration process and products on the RPs of borax-admixed MPC. Results indicated that: 1) The yield stress and plastic viscosity of MPC dramatically decreased with the borax content, and the consequences induced by final curve-fitting are basically in accordance with Bingham model. 2) The Zeta potential exhibited that borax content had no significant effect on the continuous stability of the colloidal dispersion. Moreover, results of electrochemical impedance expressed that increasing the amount of borax enhanced the concentration of ions in MPC, which further induced reduced electrical impedance. 3) Low-field nuclear magnetic resonance and analysis of thermo-gravimetry and derivative thermo-gravimetry conveyed that the addition of borax had a distinct delayed coagulation on MPC, which was mainly attributed to the combination of B(OH4)- and Mg2+ for producing complexes during hydration and then constituted the retarder layer to delay the formation of struvite compared with normal hydration. 4) XRD results indicated that the rupture of retarder layer was the direct inducement of RPs enhancement after hydration reaction had been basically completed. All results verify the interaction between retarded hydration reaction of borax and enhanced RPs, which provide an important reference for the future repairing research of MPC.

Based on the recurrence loss value and recurrence trend, a practical method for non-stationary assessment of vibration signals is proposed adopting principal component analysis (PCA). On the basis of certain observation time scales, the sample vectors of recurrence loss and recurrence trend were established respectively. By the definition of operational stationary, the two vectors were assembled into a multivariate sample matrix, and the PCA was performed on the matrix. As the assessment object of the non-stationarity of vibration signal, the statistic indicator was built using the first principal component. The reliability of the indicator was verified by assessment of several typical non-stationary signals. At the end, this indicator was used for bridge vibration signal analysis, in order to make the signal processing more accurate.

In-service bridge structural performance analysis and prediction are usually complicated and challenging because of many unknown and uncertain factors. Contrary to the traditional structural appearance inspections and load tests, structural health monitoring (SHM) can provide a perspective for online analysis, prediction, and early warning. So far, SHM has been widely used in many bridge structures, and a lot of bridge SHM data have also been collected. However, the existing studies usually focus on some independent and unsystematic analysis methods, which are hard to use widely in engineering applications to reveal the overall structural performance. This study focuses on the structural performance analysis and prediction of the highway in-service bridge. The dynamic problems in bridge SHM are pointed out firstly, followed by a detailed analysis about the characteristics of bridge SHM data. With the consideration of different characteristics, three targeted analysis methods are proposed. An urban concrete-filled steel tube (CFST) truss girder bridge (opened to traffic in 1995) is also presented, which once experienced some prominent vibration problems. The bridge SHM system is designed and stalled after several appearance inspections, load tests, and some reinforcement measures. The data mining methods proposed (distribution function, association analysis, and time-series analysis) are employed for the analysis and prediction of structural response and deterioration extent. This study can provide some references for maintenance and management and can also build a foundation for further online analysis and early warning.

The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with

ObjectivesEarly placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10–13) with cirrhosis and acute variceal bleeding (AVB). However, early TIPS criteria may overestimate the mortality risk in a significant proportion of patients, and the survival benefit conferred by early TIPS in such patients has been questioned. Alternative criteria have been proposed to refine the criteria used to identify candidates for early TIPS. Nevertheless, the true survival benefit provided (or not) by early TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies.DesignWe collected data on 1425 consecutive patients with cirrhosis and AVB who were admitted to 12 university hospitals in China between December 2010 and June 2016. Of these, 206 patients received early TIPS, and 1219 patients received standard treatment. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders.ResultsOverall, early TIPS was associated with an 80% relative risk reduction (RRR) in mortality at 6 weeks (adjusted HR=0.20; 95% CI: 0.10 to 044; pConclusionsEarly TIPS was associated with improved survival in patients with MELD ≥19 or Child-Pugh C cirrhosis but not in patients with MELD ≤11 or Child-Pugh A cirrhosis. For MELD 12–18 or Child-Pugh B patients, future studies addressing optimal selection criteria for early TIPS remain highly warranted.

AIM: To evaluate the efficacy of transitional care interventions of multidisciplinary teams for patients with cirrhosis post-TIPS. METHODS: 68 patients undergone TIPS were randomly allocated to control or intervention group. Patients in control group received conventional care, patients in the intervention group received conventional care combined with transitional care. The compliance behavior, incidence of HE and shunt dysfunction, Child-Pugh scores and ammonia of two groups were compared at 1,3,6 and 12 month post-TIPS. RESULTS: Repeated measures analysis of variance showed significant group effects from 1,3,6 and 12 month post-TIPS for compliance behavior scores of the two groups. Intervention group had significant higher compliance behavior scores than control group 1, 3 and 6 month post-TIPS respectively. The incidences of HE the intervention group were significantly lower than control group12 months after TIPS.The incidences of shunt dysfunction in the intervention group were significantly lower than control group 12 months after TIPS. The group effects ,time effects and group*time interaction showed no significant difference in Child-Pugh scores and blood ammonia between the two groups. CONCLUSION: Post-TIPS transitional care interventions increase the accessibility of patients to scientifically informed nursing, significantly improve patients' compliance behavior and health, decrease the incidence of HE and shunt dysfunction. Clinical Trial Number: The study was registered in an independent clinical trial database (www.clinicaltrials.gov; identifier: NCT02877953)( 08/23/2016). Funding Statement: The Xinjiang Shihezi Science and Technology Administration Department provided funding for the study. This work was supported by the Foundation of the Shanghai Public Health Bureau, No. 201740143; and the Project of Medical Key Specialty of Shanghai Municipality, No. ZK2015A22. Declaration of Interests: There are no conflicts of interest. Ethics Approval Statement: The study protocol was approved by the ethical committees for human investigations at the Third Affiliated Hospital of the Medical College, Shi he zi University and by the Local Department of Health and Family Planning Commission. The study protocol also fulfilled the guidelines of Good Clinical Practice in clinical trials.

This study is to establish a predictive index (PI) model of 5-year survival rate for patients with hepatocellular carcinoma (HCC) after radical resection and to evaluate its prediction sensitivity, specificity, and accuracy. Patients underwent HCC surgical resection were enrolled and randomly divided into prediction model group (101 patients) and model evaluation group (100 patients). Cox regression model was used for univariate and multivariate survival analysis. A PI model was established based on multivariate analysis and receiver operating characteristic (ROC) curve was drawn accordingly. The area under ROC (AUROC) and PI cutoff value was identified. Multiple Cox regression analysis of prediction model group showed that neutrophil to lymphocyte ratio, histological grade, microvascular invasion, positive resection margin, number of tumor, and postoperative transcatheter arterial chemoembolization treatment were the independent predictors for the 5-year survival rate for HCC patients. The model was PI = 0.377 × NLR + 0.554 × HG + 0.927 × PRM + 0.778 × MVI + 0.740 × NT – 0.831 × transcatheter arterial chemoembolization (TACE). In the prediction model group, AUROC was 0.832 and the PI cutoff value was 3.38. The sensitivity, specificity, and accuracy were 78.0%, 80%, and 79.2%, respectively. In model evaluation group, AUROC was 0.822, and the PI cutoff value was well corresponded to the prediction model group with sensitivity, specificity, and accuracy of 85.0%, 83.3%, and 84.0%, respectively. The PI model can quantify the mortality risk of hepatitis B related HCC with high sensitivity, specificity, and accuracy.

Summary Background The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. Methods In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0–3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with 125 iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. Findings Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72–207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153–201) in the irradiation group versus 147 days (124–170) in the control group (p=0·0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). Interpretation In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with 125 iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent. Funding National High-tech Research Foundation of China, National Basic Research Program of China, Jiangsu Provincial Special Program of Medical Science, National Scientific and Technical Achievement Translation Foundation, and National Natural Science Foundation of China.

A class of N-ethyl dabigatran derivatives was designed based on pharmacological strategies for inhibition of thrombin activity and the structure-activity relationship studies of the previous dabigatran derivatives. Activities of these novel compounds were predicted based on CoMFA model, and most of the compounds had comparable predicted activity with dabigatran. All of screened compounds were synthesized and characterized by (1)H NMR, (13)C NMR and HRMS. Subsequently, these compounds were evaluated inhibitory activity on thrombin. Among these compounds, 9a-9e, 9h, 9l-9n and 9p exhibited comparable inhibitory activity to dabigatran (IC50 = 1.20 nM), additionally, compound 9p (IC50 = 0.96 nM) exhibited better inhibitory activity than dabigatran. Moreover, compound 9p also exhibited a fairly good inhibitory activity for arteriovenous thrombosis with inhibition rate of (85.35 ± 0.72) %, which was comparable to that of dabigatran (85.07 ± 0.61) %. These results, along with related molecular docking studies, could provide an important basis for further development of compound 9p as a potent thrombin inhibitor.

The purpose of our study was to test the hypothesis that sorafenib-related dermatologic adverse events (AEs) as an early biomarker can predict the long-term outcomes following the combination therapy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S). The intermediate-stage hepatocellular carcinoma patients who received either TACE-S or TACE-alone treatment were consecutively included into analysis. In the TACE-S group, patients with ≥ grade 2 dermatologic AEs within the first month of sorafenib initiation were defined as responders; whereas those with grade 2 were defined as nonresponders. In the TACE-S group, the median overall survival (OS) of the responders was significantly longer than that of nonresponders (28.9 months vs. 16.8 months, respectively; p = 0.004). Multivariate analysis demonstrated that nonresponders were significantly associated with an increased risk of death compared with responders (HR = 1.9; 95% confidence Interval-CI: 1.3-2.7; p = 0.001). The survival analysis showed that the median OS was 27.9 months (95% CI: 25.0-30.8) among responders treated with TACE-S vs.18.3 months (95% CI: 14.5-22.1) among those who received TACE-alone (p = 0.046). The median time to progression was 13.1 months (95% CI: 4.4-21.8) in the TACE-S group, a duration that was significantly longer than that in the TACE-alone group [5 months (95% CI: 6.4-13.3), p = 0.014]. This study demonstrated that sorafenib-related dermatologic AEs are clinical biomarkers to identify responders from all of the patients for TACE-S therapy. Sorafenib-related dermatologic AEs, clinical biomarkers, can predict the efficacy of TACE-S in future randomized controlled trials.

Twenty-one fluorinated dabigatran derivatives were designed based on the bioisosteric principle. All derivatives were synthesised and evaluated for their thrombin inhibitory activity in vitro. Among these compounds, 14h, 14m, 14s and 14t were potent and the activity was in the range of reference drug, dabigatran. Three structural changes were introduced in these 21 compounds to elucidate the structure-activity relationship of the drugs. In addition, prodrugs of compounds 14h and 14s were developed to investigate their anticoagulant activities in vivo. In these experiments, compound 16 showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and demonstrated potent activity for inhibiting arteriovenous thrombosis with an inhibition rate of (73 ± 6) %, which was comparable to that of dabigatran etexilate (76 ± 2) %. Moreover, molecular docking studies were performed to understand the binding interactions of active compounds 14h, 14s and 14t with thrombin protein (PDB ID:1KTS). Contour maps obtained from the 3D-QSAR model are meaningful in designing more active molecules to act as direct inhibitors of thrombin.

4080 Background: The proof of the superiority of combination therapy with sorafenib and transarterial chemoembolization (TACE) over TACE alone for hepatocellular carcinoma (HCC) in term of survival...