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%。

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

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。

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的制备与性质

研究以空心玻璃微球为载体 ,用Sol gel法制备附载型复合光催化剂的过程 ,并对TiO2 ·SiO2 /beads光催化活性进行评价 .结果表明 :复合型光催化剂TiO2 ·SiO2 摩尔比存在最佳值 ,当n(TiO2 ) /m(SiO2 ) =30 /70时 ,光活性是在同样降解条件下 ,同样含量DegussaP 2 5TiO2 的 2倍左右 .同时研究制备方法、制备条件、TiO2 ·SiO2 摩尔比、TiO2 ·SiO2 /beads吸附性、活化条件、比表面等因素对附载型复合光催化剂活性的影响 .

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。

BACs-on-Beads技术对NIPT阳性结果的诊断价值

目的探讨应用BACs-on-Beads(Bo Bs)技术在无创DNA产前检测(NIPT)阳性结果中的诊断价值。方法对2015年1月至2016年6月因NIPT阳性结果在西京医院产前诊断中心进行羊水穿刺的129例孕妇进行Bo Bs检测和染色体核型分析。结果 Bo Bs共检出异常数80例,检出率62.02%。其中21三体55例、18三体10例、13三体1例、性染色体异常14例(X0 3例,XXX 3例,XXY 5例,XYY 2例,X0/XY嵌合1例),准确率依次为84.62%、71.43%、14.29%、41.18%。染色体核型分析结果与Bo Bs结果完全一致,确证了49例NIPT假阳性结果。结论 NIPT存在一定比例的假阳性结果,阳性病例必须进行进一步产前诊断,Bo Bs技术具有快速,简便,准确、高通量等优点,是快速确诊的有效手段。

BACs-on-Beads技术在快速诊断常见染色体异常中的应用

目的探讨细菌人工染色体标记-微球鉴别分离技术(BACs-on-Beads,BoBs)在快速诊断常见染色体异常中的应用。方法利用BoBs和染色体核型分析技术对856例孕妇的羊水标本进行检测,统计分析两种检测方法的一致性。结果856例孕妇共检出155例染色体异常病例,总体异常率为18.11%。两种方法同时检出141例染色体异常(包括136例非整倍体和5例嵌合体),染色体核型分析单独检出9例染色体异常(包括4例嵌合体和5例平衡易位),BoBs单独检出5例染色体微缺失/微重复。在染色体数目异常检出方面,BoBs和染色体核型分析的一致率为100%,对嵌合体检测的符合率为55.56%,对平衡易位和微缺失/微重复检测的符合率为0%。结论BoBs技术可以快速检测常见染色体数目异常及部分染色体微缺失/微重复,但存在漏诊风险。仅根据BoBs检测结果对胎儿作进一步处理存在一定风险,BoBs检测与染色体核型分析联合应用可以快速诊断常见染色畸形以减轻孕妇心理负担。

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.

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.

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.

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.

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.

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.

CHEMICAL MODIFICATION OF THE SURFACE OF CALCIUM ALGINATE GEL BEADS

The chemical modification of the surface of calcium alginate gel beads (CAGB) via grafting copolymerization with vinyl acetate (VAc) was studied. The optimum reaction conditions with activation and graft copolymerization two steps were explored. First, 5 grams CAGB with 2.5 mm initial diameter was initiated with 0.0493 mol/L K2S2O8 at 51 °C for 30 min in 15 mL 1 % PVA/H2O. Then 4.34 moi/L VAc was added dropwise and the reaction was allowed to proce at 48 °C for 3 h. The grafting efficiency could come up to 30%. It was found the stability of modified CAGB in the air and in electrolyte solutions was greatly improved.

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.

Two kinds of ketoprofen enteric gel beads(CA and CS-SA) using biopolymer alginate

To obtain expected rapid-release and sustained-release of ketoprofen gel beads, this paper adopted biopolymer alginate to prepare alginate beads and chitosan-alginate gel beads. Formulation factors were investigated and optimized by the single factor test. The release of ketoprofen from calcium alginate gel beads in pH 1.0 hydrochloric acid solution was less than 10% during 2 h, then in pH6.8 was about 95% during 45 min, which met the requirements of rapid-release preparations. However, the drug release of chitosan-alginate gel beads in pH1.0 was less than 5% during 2 h, then in pH6.8 was about 50% during 6 h and reached more than 95% during 12 h, which had a good sustained-release behavior. In addition, the release kinetics of keteprofen from the calcium alginate gel beads fitted well with the Korsmeyer–Peppas model and followed a case-II transport mechanism. However, the release of keteprofen from the chitosan-alginate gel beads exhibited a non-Fickian mechanism and based on the mixed mechanisms of diffusion and polymer relaxation from chitosanalginate beads. In a word, alginate gel beads of ketoprofen were instant analgesic, while chitosan-alginate gel beads could control the release of ketoprofen during gastrointestinal tract and prolong the drug's action time.

Transarterial chemoembolization using 40 μm drug eluting beads for hepatocellular carcinoma

AIM To assess the safety and efficacy of transarterial chemoembolization(TACE) of hepatocellular carcinoma(HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment.METHODS Drug eluting bead TACE(DEB-TACE) using a new generation of microspheres(embozene tandem,40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensatedcirrhosis.Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors(RECIST) and modified RECIST(m RECIST) guidelines applied to computed tomography or magnetic resonance imaging.Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation(OLT).This allowed for histological analysis on the treated explanted nodules.RESULTS DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality.The objective response rate of treated tumors was 72.6% and 26.7% according to m RECIST and RECIST respectively.Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases.The overall time to progression was 13 mo(11-21).CONCLUSION DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients(Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

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.