Drug-eluting beads chemoembolization combined with programmed cell death 1 inhibitor and lenvatinib for large hepatocellular carcinoma

BACKGROUND The combination of transarterial chemoembolization(TACE),lenvatinib,and programmed cell death 1(PD-1)inhibitor has been widely used in the treatment of advanced hepatocellular carcinoma(HCC)and has achieved promising results.However,there are few studies comparing whether drug-eluting beads TACE(DTACE)can bring more survival benefits to patients with large HCC compared to conventional TACE(C-TACE)in this triplet therapy.AIM To compare the efficacy and adverse events(AEs)of triple therapy comprising DTACE,PD-1 inhibitors,and lenvatinib(D-TACE-P-L)and C-TACE,PD-1 inhibitors,and lenvatinib(C-TACE-P-L)in patients with large HCC(maximum diameter≥5 cm),and analyze the prognostic factors.METHODS Following a comprehensive review of our hospital’s medical records,this retrospective study included 104 patients:50 received D-TACE-P-L,and 54 received CTACE-P-L.We employed Kaplan-Meier estimation to assess the median progression-free survival(PFS)between the two groups,utilized Cox multivariate regression analysis to identify prognostic factors,and applied theχ2 test to evaluate AEs.RESULTS The objective response rate(ORR)and median PFS were significantly higher in the D-TACE-P-L group compared to the C-TACE-P-L group(ORR:66.0%vs 44.4%,P=0.027;median PFS:6.8 months vs 5.0 months,P=0.041).Cox regression analysis identified treatment option,portal vein tumor thrombus,and hepatic vein invasion as protective factors for PFS.AEs were comparable between the two CONCLUSION D-TACE-P-L may have significantly better PFS and ORR for large HCC,while exhibiting similar AEs to C-TACE-PL.

H_4SiW_(12)O_(40)/TiO_2/beads光催化降解亚甲基蓝的研究

以钛酸四丁酯为原料,空心微珠为载体,采用溶胶-凝胶法制备TiO2/beads光催化剂载体,然后浸渍法制备出H4SiW12O40/TiO2/beads表面负载修饰型复合光催化剂,并运用SEM、XRD、FT-IR和DRS对催化剂进行表征和分析。研究了H4SiW12O40/TiO2/beads对亚甲基蓝降解的光催化活性,考察了光强度、pH值、曝气量、底物浓度和催化剂用量等对催化效率的影响。实验结果表明,在中性条件下,H4SiW12O40/TiO2/beads催化剂的投加量为0.25 g/L,浓度为7.5 mg/L的亚甲基蓝溶液在250 W的紫外灯和600 W的可见光灯下光照60 min降解率分别可达到94.5%和55%。

附载型复合光催化剂TiO_2·SiO_2/beads降解有机磷农药

研究以四异丙醇钛 [Ti( iso- O C3 H7) 4]、硅酸乙酯为原料 ,以空心玻璃微球为载体 ,用溶胶—凝胶法制备可漂浮附载型复合光催化剂 Ti O2 · Si O2 / beads的过程 ,利用附载型复合光催化剂降解有机磷农药。结果表明 ,复合型光催化剂 Ti O2 · Si O2 摩尔比存在最佳值 ,n ( Ti O2 ) / m ( Si O2 ) =30 / 70时 ,光催化剂活性最高 ,其活性是同样降解条件下、同样含量 Degussa P- 2 5Ti O2 的 2倍左右。该光催化剂比表面大 ,吸附性强。并用 XRD和

TiO_2·SiO_2/beads降解有机磷农药的研究

研究以四氯化钛 ,硅酸乙酯为原料 ,以空心玻璃微球为载体 ,用浸涂法制备TiO2 ·SiO2 /beads负载型复合光催化剂的过程。对利用负载型复合光催化剂降解有机磷农药进行了活性评价。结果表明 :TiO2 ·SiO2 /beads光活性显著提高 ,最佳光催化剂活性是同样降解条件下、同样含量的DegussaP - 2 5TiO2 光活性的 1.35倍左右。另外 ,对TiO2 ·SiO2 /beads的吸附性和比表面进行测试 ,同时从微观角度对负载型复合光催化剂的表面状态和光催化剂颗粒尺寸进行分析。

溶胶-凝胶法制备TiO_2·SiO_2/beads及其光催化性能的研究

研究以四异丙醇钛 [Ti (iso OC3 H7) 4 ]、硅酸乙酯为原料 ,以空心玻璃微球为载体 ,用溶胶 凝胶法制备可漂浮附载型复合光催化剂TiO2 ·SiO2 /beads的过程 ,利用附载型复合光催化剂降解有机磷农药。结果表明 :附载型复合光催化剂活性显著提高 ,牢固性增强 ,TiO2 ·SiO2 摩尔比存在最佳值。n (TiO2 ) /m (SiO2 ) =30 / 70时 ,光催化剂活性最高 ,其活性是同样降解条件下 ,同样含量DegussaP 2 5TiO2 的

CoPcS/TiO_2/beads及TiO_2/beads光催化降解水面漂浮植物油

以钛酸四丁酯为原料,以空心玻璃微珠为载体,采用溶胶-凝胶法制备出TiO2/beads光催化剂,用浸渍法制备出CoPcS/TiO2/beads光催化剂。研究了TiO2/beads及CoPcS/TiO2/beads光催化降解水面漂浮植物油的最优条件。结果表明,酸性或中性条件下,375 W中压汞灯照射2～3 h,TiO2/beads与CoPcS/TiO2/beads的投加量分别为3 g与1 g时,植物油的去除率达90%以上,投加微量的H2O2,可大大提高两者的光催化去除率。

Fabrication of Core-Shell Hydrogel Bead Based on Sodium Alginate and Chitosan for Methylene Blue Adsorption

A novel core-shell hydrogel bead was fabricated for effective removal of methylene blue dye from aqueous solutions.The core,made of sodium alginate-g-polyacrylamide and attapulgite nanofibers,was cross-linked by Calcium ions(Ca^(2+)).The shell,composed of a chitosan/activated carbon mixture,was then coated onto the core.Fourier transform infrared spectroscopy confirmed the grafting polymerization of acrylamide onto sodium alginate.Scanning electron microscopy images showed the core-shell structure.The core exhibited a high water uptake ratio,facilitating the diffusion of methylene blue into the core.During the diffusion process,the methylene blue was first adsorbed by the shell and then further adsorbed by the core.Adsorption tests showed that the coreshell structure had a larger adsorption capacity than the core alone.The shell effectively enhanced the adsorption capacity to methylene blue compared to the single core.Methylene blue was adsorbed by activated carbon and chitosan in the shell,and the residual methylene blue diffused into the core and was further adsorbed.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

BACKGROUND The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization(DEB-TACE)as neoadjuvant therapy before liver transplantation(LT)for advanced-stage hepatocellular carcinoma(HCC)and to analyze the prognostic factors.AIM To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC.METHODS A total of 99 individuals diagnosed with advanced HCC were studied retrospectively.The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT:DEB-TACE group(n=45)and control group(n=54).The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus(PVTT).The DEB-TACE group consisted of two subgroups:Group A(n=31)without PVTT and group B(n=14)with PVTT.The control group also had two subgroups:Group C(n=37)without PVTT and group D(n=17)with PVTT.Data on patient demographics,disease characteristics,therapy response,and adverse events(AEs)were collected.The overall survival(OS)and recurrence-free survival(RFS)rates were assessed using Kaplan-Meier curves.Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS.RESULTS The DEB-TACE group exhibited an overall response rate of 86.6%.Following therapy,there was a significant decrease in the median alpha-fetoprotein(AFP)level(275.1 ng/mL vs 41.7 ng/mL,P<0.001).The main AE was post-embolization syndrome.The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group(68.9%vs 38.9%,P=0.003;86.7%vs 63.0%,P=0.008).Within the subgroups,group A had higher 2-year rates of RFS and OS compared to group C(71.0%vs 45.9%,P=0.038;83.8%vs 62.2%,P=0.047).The 2-year RFS rate of group B was markedly superior to that of group D(64.3%vs 23.5%,P=0.002).Results from multivariate analyses showed that pre-LT DEB-TACE[hazard ratio(HR)=2.73,95%confidence interval(CI):1.44-5.14,P=0.04],overall target tumor diameter≤7 cm(HR=1.98,95%CI:1.05-3.75,P=0.035),and AFP level≤400 ng/mL(HR=2.34;95%CI:1.30-4.19,P=0.009)were significant risk factors for RFS.Additionally,pre-LT DEBTACE(HR=3.15,95%CI:1.43-6.96,P=0.004)was identified as a significant risk factor for OS.CONCLUSION DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

CoPcS／TiO2／beads及TiO2／beads光催化降解水面浮油

以钛酸四丁酯为原料,空心玻璃微珠(beads)为载体,采用溶胶-凝胶法制备出TiO2/beads光催化剂,用浸渍法制备出CoPcS/TiO2/beads新型光催化剂.研究了利用TiO2/beads及CoPcS/TiO2/beads光催化剂降解水面漂浮植物油的最优条件.结果表明:(1)溶胶-凝胶法制备TiO2/beads的最佳条件为:空心玻璃微珠浸渍3次,450～550℃下焙烧2 h.用CoPcS对TiO2/beads进行改性时,TiO2/beads的最佳浸渍时间为30 min.(2)在中性或酸性条件下,375 W中压汞灯光照2～3 h,TiO2/beads与CoPcS/TiO2/beads的最佳用量分别为3 g和1 g(植物油3 g),在此条件下,植物油的去除率都高达90%.(3)微量H2O2对TiO2/beads和CoPcS/TiO2/beads的光催化活性都有很大的提高.对于TiO2/beads催化剂,H2O2的最佳用量为5～11 mmol/L;对于CoPcS/TiO2/beads催化剂,H2O2的最佳用量为5～30 mmol/L.(4)新型光催化剂CoPcS/TiO2/beads比TiO2/beads具有更好的除油性能.

A Different Brachistochrone Problem with Counterintuitive Results

A problem similar to the famous brachistochrone problem is examined in which, instead of a smooth curve, the path consists of two straight-line sections, one slant and one horizontal. The condition for minimum sliding time is investigated, producing results that are both counterintuitive and interesting.

Release Profile of Lansoprazole Encapsulated in Sodium Alginate Beads

Symptomatic gastroesophageal reflux disease (GERD) affects 11% of the population worldwide. Lansoprazole was the second commercially available proton pump inhibitor, recommended for healing and symptomatic relief of reflux esophagitis. This work presents the encapsulation of lansoprazole in sodium alginate beads, generating a controlled release system of the encapsulated drug. The quantification of lansoprazole contents from the encapsulated raw material was carried out, using the methodology prescribed in the Brazilian Pharmacopoeia 5th edition, with adjustments, the encapsulation efficiency and the release profile. Experimental tests were performed using scanning UV-Vis spectrophotometry. Encapsulation efficiency was 100%, obtained from the measurement of the absorbance of the filtrate. Release profile shows the concentration of lansoprazole in the external environment was 4 μg/mL (16%) immediately after 10 min. Concentration of lansoprazole released by the beads follows a linear dynamic as a function of time, with a maximum release equivalent to 25 μg/mL after 210 min (100%). The rate of release is influenced by pH, being higher by 7.4. Beads subjected to heat treatment have a higher release rate at a temperature of 30 °C when compared to a temperature of 60 °C. Increase in temperature decreases the diameter of the beads. The presence of lansoprazole affects the release curve. The absorption rate of the microbeads with lansoprazole is 0.83, and the absorption rate of the microbeads without lansoprazole is 0.58. Sodium alginate beads have a good controlled release effect on lansoprazole.

Pb(Ⅱ) biosorption using chitosan and chitosan derivatives beads: Equilibrium, ion exchange and mechanism studies

The study examined the adsorption of Pb（II） ions from aqueous solution onto chitosan, chitosan-GLA and chitosan-alginate beads. Several important parameters influencing the adsorption of Pb（II） ions such as initial pH, adsorbent dosage and different initial concentration of Pb（II） ions were evaluated. The mechanism involved during the adsorption process was explored based on ion exchange study and using spectroscopic techniques. The adsorption capacities obtained based on non–linear Langmuir isotherm for chitosan, chitosan-GLA and chitosan-alginate beads in single metal system were 34.98, 14.24 and 60.27 mg/g, respectively. However, the adsorption capacity of Pb（II） ions were reduced in the binary metal system due to the competitive adsorption between Pb（II） and Cu（II） ions. Based on the ion exchange study, the release of Ca2＋, Mg2＋, K＋ and Na＋ ions played an important role in the adsorption of Pb（II） ions by all three adsorbents but only at lower concentrations of Pb（II） ions. Infrared spectra showed that the binding between Pb（II） ions and the adsorbents involved mostly the nitrogen and oxygen atoms. All three adsorbents showed satisfactory adsorption capacities and can be considered as an efficient adsorbent for the removal of Pb（II） ions from aqueous solutions.

Synthesis of phosphate-embedded calcium alginate beads for Pb(Ⅱ) and Cd(Ⅱ) sorption and immobilization in aqueous solutions

The phosphate-embedded calcium alginate beads were successfully synthesized based on sodium alginate, calcium dihydrogen phosphate and sodium hydrogen carbonate. Scanning electron microscopy, Fourier transformed infrared (FTIR) spectroscopy and X-ray diffraction (XRD) were conducted to characterize the morphology and structure of the phosphate-embedded calcium alginate beads. The effects of pH and the initial concentration of the metal ions on Pb(II) and Cd(II) sorption by the beads were investigated. The optimal pH values for Pb(II) and Cd(II) sorption are 4.0 and 5.5, respectively. The optimal initial concentrations of Pb(II) and Cd(II) are 200 mg/L and 25 mg/L, correspondingly, and the removal efficiencies are 94.2% and 80%,respectively. The sorption mechanism is that the heavy metal ions accessed the beads firstly due to the large surface area, combinedwith OH?, and then precipitated with phosphate radical, which was proven by FTIR and XRD. The sorption of Pb(II) and Cd(II) isfitted to Langmuir isotherm model with R2 values of 0.9957 and 0.988, respectively. The sorption capacities of Pb(II) and Cd(II) are263.16 mg/g and 82.64 mg/g, respectively. The results indicate that the phosphate-embedded calcium alginate beads could be appliedto treating Pb(II)/Cd(II)-containing wastewater and it could be implied that the synthesized beads also could be used as a kind of soil ameliorant for remediation of the heavy metal contaminated paddy soil.

Microsatellite Enrichment from AFLP Fragments by Magnetic Beads

A simple and efficient method was presented for isolating microsatellite DNA markers from peanut (Arachis hypogaea L.) genome. The genomic DNA was converted into pre-amplified AFLP fragments and hybridized with biotin-labeled SSR probes. Then the hybrid mixture was used to incubate with magnetic beads coated with streptavidin. After washing to remove the non-SSR fragments, the eluted single-strand DNA, which was cloned and sequenced, was largely enriched for microsatellites. Primers can then be designed according to the sequence flanking the repeat motifs and used for polymorphism analysis. The whole experiment can be completed within one week and can be employed as a reliable option for any molecular laboratory to develop SSR markers.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma

AIM To assess the usefulness of intra-arterial contrastenhanced ultrasonography(IAUS) during transarterial chemoembolization(TACE) with drug-eluting beads(DEB) for hepatocellular carcinoma(HCC).METHODS Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography(CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEBTACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using m RECIST(CR/PR/SD/PD).RESULTS The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5%(24/39).CONCLUSION A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Conventional vs drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma

Transarterial chemoembolization(TACE) is the current standard of therapy for patients with intermediatestage hepatocellular carcinoma(HCC) according to the Barcelona Clinic Liver Cancer classification. The concept of conventional TACE(cTACE) is the selective obstruction of tumor-feeding artery by injection of chemotherapeutic agents, leading to ischemic necrosis of the target tumor via cytotoxic and ischemic effects. Drugeluting beads(DEBs) have been imposed as novel drugdelivering agents for TACE, which allows for higher concentrations of drugs within the target tumor and lower systemic concentrations compared with cTACE. Despite the theoretical advantages of DEB-TACE, it is still controversial in clinical practice as to whether DEBTACE is superior to cTACE in regard to overall survival and treatment response. In this review article, we summarize the clinical efficacy and safety of DEB-TACE for patients with intermediate or advanced stage HCC in comparison with cTACE.

Highly efficient generation of GGTA1 knockout pigs using a combination of TALEN m RNA and magnetic beads with somatic cell nuclear transfer

The transcription activator-like effector nuclease （TALEN） technique combined with the somatic cel nuclear transfer （SCNT） method has been successfuly applied for creating geneticaly modiifed pigs. However, methods for isolating cels with bialelic indels requires further improvement because of the relatively low enrichment efifciency of mutated somatic cels. Moreover, little is known regarding the off-target effects of the TALEN system and the heredity of TALEN-modiifed pigs. In this study, an efifcient method to increase the enrichment efifciency of TALEN-mediated bialelic knockout （KO） cels was established, and corresponding geneticaly modiifed pigs with the expected genotype were generated whose off-target effect, fertility and heredity characteristics were aslo evaluated. Two TALEN pairs were constructed to target the porcine α-1,3-galactosyltransferase （GGTA1） gene locus. TALEN mRNA was transfected into the ear ifbroblasts folowed by the enrichment of α-Gal nul cels of minipigs using isolectin B4 （IB4） lectin and magnetic beads. A total of 115 cel colonies were formed and validated to beGGTA1 KO cels by sequencing and 10 bialelic KO cel colonies were used as nuclear donors for SCNT. ThirtyGGTA1 bialelic KO piglets were successfuly delivered and grew normaly. Seventeen potential off-target sites were investigated, and no off-target events were detected in the live piglets. To determine the fertility and heredity characteristics of TALEN-modiifed pigs, 10 mature founders were mated with each other and the mutations were determined to be transmitted to the F1 piglets. We established a robust and safe technology for developing geneticaly modiifed pig lines with expected genotypes for agricultural breeding and biomedical application.

Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

Transarterial chemoembolization(TACE) is a widely used standard treatment for patients with hepatocellular carcinoma(HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia(conventional TACE). Recently, drugeluting beads(DC Beads?) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads? can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads? substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drugeluting beads for the treatment of HCC and discuss future therapeutic possibilities.

Advances in the treatment of hepatocellular carcinoma using drug-eluting beads

Hepatocellular carcinoma(HCC)is one of the most common types of malignant tumor.Although radical surgery and liver transplantation are possible cures for the disease,most patients are beyond the optimum stage for radical treatment at the time of diagnosis.Transarterial chemoembolization(TACE)is the first choice of treatment for advanced HCC.Owing to the widespread use of conventional TACE(cTACE),the problems with this treatment cannot be ignored.Drug-eluting beads(DEBs),a new type of embolization material,appear to overcome the problems of cTACE,and they have other advantages such as synchronous controlled continuous drug release after chemotherapy and embolization and low blood concentrations after treatment.This review summarizes the recent advances in the use of DEB-TACE to treat HCC.

Effects of Polyethylene Oxide Concentration on the Size of Beads in Electrospun Beaded Nanofibers

Embedding particle drugs in beaded nanofibers by electrospinning has been shown a potential approach to control drug release in tissue engineering. The bead size is one of the critical parameters in controlling the drug release rate. In this study,the relationship between polymer concentration and beads size was investigated. Aqueous polyethylene oxide( PEO) solutions with different concentrations were prepared to obtain various beaded nanofibers by electrospnning. Optical microscope and scanning electron microscope( SEM) were used to observe the variation tendency of bead size. With an increase in the polymer concentration,the diameter of fibers between beads became bigger,while the fiber uniformity improved. In addition, the polymer concentration influenced the distribution of bead diameter. Higher polymer concentration would reduce the possibility of small-sized beads formation and improve the uniformity of bead diameter. The study provides a possible way to control the size of beads,which is helpful for further research on the control of particle drug release.