超声引导下空芯针和针吸活检对乳腺癌内乳淋巴结诊断价值的比较

目的:评估超声引导下空芯针活检(core needle biopsy,CNB)和针吸活检(fine needle aspiration,FNA)对乳腺癌内乳淋巴结(internal mammary node,IMN)转移的诊断价值。方法:回顾性分析2012年5月至2020年10月河北医科大学第四医院496例行超声引导下IMN穿刺的乳腺癌患者临床资料,其中CNB组374例、FNA组122例,采用一致性Kappa检验分析CNB、FNA的诊断效能,计算诊断的敏感度、特异度等指标。亚组分析不同大小及类型IMN的CNB、FNA诊断效能及影响标本满意度的因素。结果:CNB组和FNA组穿刺标本不满意度分别为5.6%(21/374)和3.3%(4/122),差异无统计学意义(P>0.05)。剔除不满意标本后比较CNB、FNA的诊断效能,其Kappa值分别为0.817、0.907。亚组分析显示IMN厚径<0.5 cm组和0.5~0.9 cm组中,CNB、FNA的Kappa值分别为0.877、1.000和0.772、0.783(均P<0.01);IMN厚径≥1.0 cm组中,CNB组的假阴性率为3.4%(1/29),FNA组无假阴性。结论:对于IMN定性诊断,FNA诊断效能更高,由于IMN一般较小且位置特殊,FNA也是更安全的穿刺方法。

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence,the management of gout remains suboptimal.The intermittent nature of the gout makes the long-term urate-lowering therapy(ULT)particularly important for gout management.However,patients are reluctant to take medication day after day to manage incurable occasional gout flares,and suffer from possible long-term toxicity.Therefore,a safe and easy-tooperate drug delivery system with simple preparation for the long-term management of gout is very necessary.Here,a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal.This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention.Furthermore,its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models.Besides,the drug co-delivery system could help avoid long-term daily oral colchicine,a drug with a narrow therapeutic index.This system also avoids mass injection of uricase by improving its stability,enhancing the clinical application value of uricase.In general,this two-drug system reduces the dosage of uricase and colchicine and improves the patient’s compliance,which has a strong clinical translation.

Pure drug nano-assemblies: A facile carrier-free nanoplatform for efficient cancer therapy

Nanoparticulate drug delivery systems(Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity.Recently, pure drug nano-assemblies(PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Albumin mediated reactive oxygen species scavenging and targeted delivery of methotrexate for rheumatoid arthritis therapy

Rheumatoid arthritis(RA)is a common chronic systemic autoimmune disease.Although there are a variety of treatments for RA,the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs(DMARD),which would induce obvious side-effect in patients after long-term administration.Herein,an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin nanomedicine.The hydrophobic drug methotrexate(MTX)could induce self-assembly of superoxide dismutase(SOD)and human serum albumin(HSA)to form HSA-SOD-MTX nanoparticle.After intravenous injection,dual-modal imaging including fluorescence imaging or single-photon emission computed tomography(SPECT)/CT imaging exhibits high accumulation of cyanine 5.5(Cy5.5)or 125l labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis(CIA)mice.Importantly,using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species(ROS)and MTX to suppress inflammation,HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other groups.Micro-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA-SOD-MTX nanoparticles is significantly relived,which was further demonstrated by the histological analysis and the inflammatory factors measurement.The synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side effects.Therefore,our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX,which may provide the reference for clinical RA treatment.

Facile preparation of^(177)Lu-microspheres for hepatocellular carcinoma radioisotope therapy

As one of the most common cancers in the world,hepatocellular carcinoma(HCC)has become a major threat to human health.Radioembolization is a first-line option for the treatment of HCC,especially when other conventional treatments fail or there exist some relative contraindications.Herein,we developed a facile and efficient method for preparing ^(177)Lu-microspheres potentially useful for precise radioembolization therapy of HCC.The radiolabeling efficiency of ^(177)Lu-microspheres was as high as 96.8%±0.5%,and the radiolabeling process did not alter the morphology of the mother microspheres.The SPECT/CT studies enabled by the unique emissions of ^(177)Lu suggested that almost no ^(177)Lu ion loaded by the microspheres was released over more than 32 d in vivo,which led to remarkable inhibition effect on the growth of HepG2 tumors subcutaneously transplanted in mice.The current approach may thus offer promising ^(177)Lu-microspheres for clinical radioembolization of HCC.