摘要：作为一种新兴的联合治疗策略,肿瘤化学免疫治疗拓展了传统化疗药物的潜在可能性,利用某些化疗药物诱发免疫原性细胞死亡(ICD)激活抗肿瘤免疫应答,提升肿瘤治疗效率.本文设计了一种ICD和免疫激动剂协作的树形高分子纳米平台作为极简“原位”肿瘤疫苗用于高效的化学免疫治疗.利用树状高分子PAMAM担载ICD引发药物DOX以及免疫激动剂CpG,该DOX@PAMAM/CpG(简称DPC)纳米粒子物理性能适宜,通过便捷的瘤内注射可在肿瘤组织良好蓄积和内化,并最大限度地降低全身毒性.在CpG的协助下该纳米粒子可引发强劲的ICD并激活全面的抗肿瘤免疫反应,体内动物实验证实该DPC纳米粒子对侵袭性黑色素瘤具有显著的抑制.本研究为肿瘤化学免疫治疗纳米递药平台的构建提供了一种切实可行的策略.

摘要：电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸附能力、具有高灵敏度和准确性的电化学一氧化氮传感器.其对一氧化氮的物理和化学吸附能力分别来自于电极的高比表面积和丰富的羧基官能团.此外,柔软的电极可以与脑组织的力学性能相匹配,实现了一个高度适应的电极/组织界面.由此设计的颅内一氧化氮传感器表现出迄今为止所报道文献中最高的灵敏度,为3245 pA nmol^(-1)L,检测限为0.1 nmol L^(-1).电极在植入后未观察到显著的炎症反应以及过量的一氧化氮表达,提高了检测的准确性.该传感器成功捕捉了大脑中的一氧化氮波动,并实现了对多个脑区的同时检测,促进了对大脑中一氧化氮生理病理作用的研究.

摘要：设计和制备具有优异防污能力的可注射防粘连材料对预防手术后组织和器官的粘连具有重要的意义.在此,我们将含有羟基的氨基酸衍生物引入水凝胶的制备中,通过N-丙烯酰丝氨酸(ASer)的自由基聚合制备了一种新型的氢键交联水凝胶(PASer).结果发现一个甲基取代基的存在会对分子间氢键相互作用产生明显的影响:与聚(N-丙烯酰苏氨酸)(PAThr)水凝胶相比,PASer水凝胶具有较低的成胶浓度和增强的力学性能.值得一提的是,亲水性羟基使PASer水凝胶能够有效抵抗蛋白质吸附和细胞粘附.PASer水凝胶具有优异的力学性能、可注射性、自融合性、良好的生物相容性和适宜的体内停留时间,符合临床对术后抗粘连材料的要求.体内研究实验结果表明,PASer水凝胶在建立的小鼠腹壁缺损模型中可以有效预防术后腹膜粘连发生.

摘要：目的:作为遗传研究中最常用的设计之一,基于家系数据的实验设计因其优势而得到了广泛认可,例如家系数据在人群分层和混合情况下表现出来的稳健性。在疾病风险预测中,研究者对如何基于家系遗传数据,寻找和分析遗传标记的作用非常感兴趣。本研究旨在开发一种新的统计方法,用于基于家系数据的遗传风险预测。创新点:期望新方法能够捕捉小或中等边际效应的遗传因子,及其相互作用,与基于家族史或家系数据的现有风险预测方法相比,具有更高的预测准确性。方法:在这项研究中,我们提出了集群化似然比(ELR)的新方法,Fam-ELR,用于家系数据的基因组疾病风险预测。Fam-ELR采用集群化的受试者工作特征曲线(ROC)方法来考虑家系样本内部的相关性,并使用计算有效的集群树进行变量选择和模型构建。结论:通过模拟,Fam-ELR显示了其在各种疾病遗传模型和谱系结构中的稳健性,并且获得了比现有的两种基于家系数据的风险预测方法更好的性能。同时,在基于全基因组行为障碍家系数据集的实际应用中,Fam-ELR展示了其将潜在风险预测因子和其相互作用整合到模型中以提高准确性的能力,尤其是在全基因组水平上。通过比较现有方法,例如遗传风险评分方法等,Fam-ELR被证实具有将较小或中等边际效应的遗传变异及其相互作用纳入改进的风险预测模型的能力。因此,它是一种强有力且实用的方法,适用于基于家系数据的高维度遗传风险预测中,特别是对于病因未知或知之甚少的人类复杂疾病。

摘要：Three-dimensional(3D)printing has attracted increasing research interest as an emerging manufacturing technology for devel-oping sophisticated and exquisite architecture through hierarchical *** has also been employed in various advanced industrial *** development of intelligent biomedical engineering has raised the requirements for 3D printing,such as flexible manufacturing processes and technologies,biocompatible constituents,and alternative ***,state-of-the-art 3D printing mainly involves inorganics or polymers and generally focuses on traditional industrial fields,thus severely limiting applications demanding biocompatibility and *** this regard,peptide architectonics,which are self-assembled by programmed amino acid sequences that can be flexibly functionalized,have shown promising potential as bioinspired inks for 3D ***,the combination of 3D printing and peptide self-assembly poten-tially opens up an alternative avenue of 3D bioprinting for diverse advanced ***,a small but innovative nation,has significantly contributed to 3D bioprinting in terms of scientific studies,marketization,and peptide architectonics,including modulations and applications,and ranks as a leading area in the 3D bioprinting *** review summarizes the recent progress in 3D bioprinting in Israel,focusing on scientific studies on printable components,soft devices,and tissue *** paper further delves into the manufacture of industrial products,such as artificial meats and bioinspired supramolecular architectures,and the mechanisms,physicochemical properties,and applications of peptide ***,Israel contributes significantly to the field of 3D bioprinting and should thus be appropriately recognized.

摘要：Introduction Mandibular segmental defects result in significant cosmetic and functional ***,the reconstruction of both the contour and function of the mandible is a challenging *** present,autologous vascularized fibula transplantation is the most common method to reconstruct a mandible with long-span defects[1].

摘要：Type 1 diabetes is caused by insulin deficiency due to the loss of beta cells in the islets of *** severe cases,islet transplantation into the portal vein is ***,due to the loss of transplanted islets and the failure of islet function,the 5-year insulin independence rate of these patients is<50%.In this study,we developed a long-term,insulin-secreting,3 Dbioprinted construct implanted subcutaneously with the aim of preventing islet *** bioprinted construct was fabricated by the multi-layer bioprinting of beta-cell(mouse insulinoma-6:MIN-6)-encapsulated alginate bioink and poly(caprolactone)biodegradable polymer.A glucose response assay revealed that the bioprinted constructs proliferated and released insulin normally during the 4-week in vitro *** MIN-6 generated clusters with a diameter of 100-200μm,similar to the original pancreatic islets in the *** an in vivo study using type 1 diabetes mice,animals implanted with bioprinted constructs showed three times higher insulin secretion and controlled glucose levels at 8 weeks after *** the implanted,bioprinted constructs had a positive effect on insulin secretion in the experimental animals,the survival rate of the implanted group(75%)was three times higher than that of the non-implanted group(25%).The results suggest that the proposed,3 D-bioprinted,subcutaneous construct can be a better alternative to portal vein islet transplantation.

摘要：创面处理的原则,包括清创、创面准备和使用涉及改变创面生理以促进愈合的新技术,在试图治愈慢性糖尿病相关的足溃疡时是至关重要的。此外,糖尿病相关的足溃疡的发病率和治疗成本不断上升,这就需要结合作为金标准的多学科治疗已有共识,运用高质量的疗效和成本效益证据来支持和加强慢性糖尿病相关的足溃疡创面愈合的干预措施。本指南是2023年国际糖尿病足工作组(IWGDF)针对促进糖尿病患者足溃疡愈合的干预措施的循证指南。它是对2019年IWGDF指南的更新。我们遵循推荐、评估、发展、评价分级(GRADE)方法,以患者-干预-对照-结果(PICO)形式设计临床问题从而得出重要结果,进行系统综述,制定评判表汇总,并为每个问题撰写推荐和理由。每条推荐的形式都是基于系统综述中发现的证据,并使用GRADE评判汇总项目,包括理想和不理想的效果、证据的可信度、对患者的价值、所需的资源、成本效益、公平性、可行性和可接受性;我们制定的推荐由作者同意并由独立专家和利益相关者审查。根据系统综述和从证据到决策过程的结果,我们提出29条推荐。我们对使用干预措施改善糖尿病患者足溃疡的愈合提出了一些有条件的支持性推荐。这些推荐包括蔗糖八硫酸盐敷料的使用,对手术后的创面使用负压疗法,使用胎盘衍生产品,使用自体白细胞、血小板、纤维蛋白贴剂,使用局部氧疗,以及使用高压氧,但我们强调在任何情况下这些推荐应在单独应用最佳标准治疗无法治愈伤口且有资源可用于干预的情况下使用。这些关于创面愈合的推荐应该有助于提高糖尿病伴足溃疡患者的疗效,我们希望这些推荐能得到广泛的实施。然而,尽管作为推荐基础的许多证据的准确性正在提高,但总体上仍然很差,我们鼓励在这一领域进行更多、质量更好的试验,包括那些有关卫生经济学分析的试验。

摘要：Three-dimensional(3D)tumor models prepared from patient-derived cells have been reported to imitate some of the biological development processes of in situ tumors in *** 3D tumor models share several important characteristics with their in vivo tumor ***,their applications in tumor modeling,drug screening,and precision-targeted treatment are ***,the establishment of tumormodels is subject to several challenges,including advancements in scale size,repeatability,structural precision in time and space,vascularization,and the tumor ***,bioprinting technologies enabling the editorial arrangement of cells,factors,and materials have improved the simulation of tumormodels in *** the 3D bioprinted tumor models,the organoidmodel has been widely appreciated for its advantages of maintaining high heterogeneity and capacity for simulating the developmental process of tumor *** this review,we outline approaches and potential prospects for tumor model bioprinting and discuss the existing bioprinting technologies and bioinks in tumor model *** multidisciplinary combination of tumor pathology,molecular biology,material science,and additive manufacturing will help overcome the barriers to tumor model construction by allowing consideration of the structural and functional characteristics of in vitro models and promoting the development of heterogeneous tumor precision therapies.

摘要：减轻组织的机械性压力在治愈糖尿病相关的足溃疡所需的多种干预措施中最为重要。本文是2023年国际糖尿病足工作组(IWGDF)发布的减压治疗促进糖尿病相关的足溃疡愈合的循证指南,也是对2019年IWGDF指南的更新。我们遵循推荐、评估、发展和评价分级(GRADE)方法学,以患者-干预-比较-结局(patient-intervention-control-outcome,PICO)模式设计临床问题和重要结果,进行系统评价和Meta分析,制定评判表汇总,为每个问题编写推荐和理由。每项推荐都是基于系统综述中发现的证据,在无证据情况下则采用专家意见,以及对判断项目的GRADE等级总结进行仔细权衡,包括可预期和不可预期的影响、证据的确定性、患者价值、所需资源、成本效益、公平性、可行性和可接受性。为了治愈糖尿病患者神经性前足底或中足底溃疡,要使用不可拆卸的齐膝高减压装置作为首选减压干预措施。如果患者存在对不可拆卸减压装置的禁忌证或不能耐受,考虑使用可拆卸齐膝(或踝)高减压装置作为减压干预措施的第二选择。如果无可用的减压装置,考虑使用合适的鞋具结合毡制泡沫作为减压干预措施的第三选择。如果这种非手术减压治疗不能治愈前足底溃疡,可以考虑跟腱延长术、跖骨头切除术、关节置换术或跖骨截骨术。为了治疗继发于屈趾畸形的神经性足底或小趾远端溃疡,可行趾屈肌腱切开术。为了促进后足、非足底或并发感染或缺血的溃疡的愈合,提出了进一步的推荐。所有推荐都已在减压临床路径中进行了总结,以帮助促进本指南在临床实践中的实施。这些减压推荐将帮助医务人员为糖尿病相关的足溃疡患者提供最佳的治疗和预后,降低患者感染、住院和截肢的风险。