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Summary Background Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. Methods AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov , NCT02329860 . Findings Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand–foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. Interpretation Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. Funding Jiangsu Hengrui Medicine.

Carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were selected as the carrier and polypyrrole (PPy) as functional agent to synthesize PPy/MWCNTs dielectric nanofillers via FeCl3 oxidative polymerization of pyrrole (Py) on the surface of MWCNTs-COOHs, and then poly(vinylidene fluoride) based dielectric nanocomposites (PPy/MWCNTs/PVDF) were fabricated by direct melting blending. The effects of the PPy/MWCNTs dielectric nanofillers on the changes of phase behaviors and the mechanical, thermal and dielectric properties of the PPy/MWCNTs/PVDF dielectric nanocomposites were investigated. The results indicated that PPy/MWCNTs/PVDF dielectric nanocomposites showed higher mechanical strength within a certain range of PPy/MWCNTs nanofillers content. When the PPy/MWCNTs content was 10 wt.%, the tensile strength and elastic modulus of the nanocomposites reached 60.2 MPa and 610 MPa respectively, which increased by 24 % and 75 %, in contrast to those of MWCNT-COOH/PVDF dielectric nanocomposites. Dielectric properties tests revealed that the introduction of PPy induced the formation conductive networks and β-type PVDF, and thus enhancing the dielectric constant. the resultant PPy/MWCNTs/PVDF dielectric nanocomposites reached the percolation threshold at the PPy/MWCNTs content of 12 wt.%. The corresponding dielectric constant reached 83, which was 10 times of pure PVDF. Meanwhile, the dielectric constant was also much higher than MWCNTs-COOH/PVDF. Differential scanning calorimeter (DSC) found that the melting and crystallization temperatures of the two nanocomposites were greatly improved compared with pure PVDF, indicating that the addition of dielectric nanofiller improved the thermal property of the nanocomposites.

We report on a wireless magnetoelastic-sensing device for the assay of pathogen with Escherichia coli O157:H7 (E. coli) as a target using chitosan-modified magnetic Fe3O4 nanoparticles (CMNPs) as signal-amplifying tags. At suitable pH the CMNPs, Fe3O4 nanoparticles functionalized with a layer of chitosan, bind to negatively charged E. coli through electrostatic attraction. The E. coli attached CMNPs are magnetically bound to the surface of the magnetoelastic sensor, resulting in enhanced mass loading on the sensor surface that in turn decreases its resonance frequency allowing quantification of E. coli concentrations. The sensor shows a linear response to the logarithmic concentration of E. coli in the range of 10 cells mL−1 to 3.7 × 108 cells mL−1, with a detection limit (LOD) of 10 cells mL−1. Small molecules such as albumin bovine and ovalbumin show no interference on the detection.

A wireless magnetoelastic-sensing device for the detection of polycyclic aromatic hydrocarbons (PAHs) with anthracene as the model target is reported using humic acid-modified magnetic Fe 3 O 4 nanoparticles (HMNPs) as signal-amplifying tags. A sandwich-type detection strategy involves the humic acid (HA)/chitosan composite self-assembled on the polyurethane-protected sensor surface and HMNPs, both of which flank the anthracene target in sequence. As the HMNPs-combined anthracene absorbs to the sensor surface, there is an increase in the mass load on the sensor, and consequently a decrease in resonance frequency. Under optimal conditions, the sensor shows a linear response to polycyclic aromatic hydrocarbons with sensitivity depending on the benzene rings. The sensor shows the largest sensitivity to benzo[ a ]pyrene due to its 5 ring with a detection limit of 3 nM. Tap water, river water and spring water were analyzed with this sensor.