HER2阳性乳腺癌治疗模式的进展和优化

随着抗人表皮生长因子受体2（human epidermalgrowth factor receptor 2 ，HER2）抗肿瘤药物的不断出现及广泛应用，HER2 阳性乳腺癌患者的治疗以及预后得到了显著的改善。PEONY 研究结果的发布再次奠定了帕妥珠单抗+曲妥珠单抗的双靶治疗模式在新辅助治疗领域中的地位；结合TRYPHAENA 和TRAIN-2 两项研究，紫杉类+铂类应该是抗HER2 双靶治疗的首选化疗方案，疗程宜6 个周期。结合中国乳腺癌新辅助治疗专家共识和辅助APT 研究的最新随访结果，新辅助治疗适用人群为肿瘤直径超过3 cm 和/或淋巴结阳性的患者，新辅助治疗后如果没有获得pCR，T-DM1 应该是辅助治疗的首选模式，帕妥珠单抗+曲妥珠单抗的双靶辅助模式期待PEONY 研究的后续生存随访；对于没有淋巴结转移的小肿瘤（≤3 cm）低危患者可以考虑免除新辅助治疗，采取直接手术+术后给予曲妥珠单抗联合单药紫杉醇的辅助治疗模式。曲妥珠单抗+帕妥珠单抗联合紫杉类药物依然是晚期HER2 阳性患者的标准一线治疗；对于中国患者而言，吡咯替尼联合卡培他滨可以作为二线的优选；T-DM1 可以作为三线及后线选择；曲妥珠单抗、帕妥珠单抗、T-DM1 治疗失败的情况下，DS-8201 成为新的选择模式；伴有脑转移的HER2 阳性晚期乳腺癌患者则可以考虑图卡替尼与曲妥珠单抗和卡培他滨的联合治疗模式。     

星点设计-效应面法优化pH值响应及线粒体靶向双功能金丝桃苷脂质体的处方及其体外评价

目的 优化线粒体靶向金丝桃苷脂质体（DLD/Hyp-Lip）制备的最佳处方，并研究研究其在胎牛血清中的稳定性及体外释放行为，考察其线粒体靶向性。方法 采用薄膜分散法制备DLD/Hyp-Lip，以包封率和载药量为考察指标进行单因素实验，考察磷脂总量与金丝桃苷（hyperoside，Hyp）用量比、二硬脂酰磷脂酰乙醇胺-聚乙二醇（DSPE-PEG）与DLD用量比等条件对DLD/Hyp-Lip的影响，结合星点设计-效应面法优化DLD/Hyp-Lip处方。使用透射电子显微镜和粒径仪观察测定脂质体粒子外观、平均粒径和Zeta电位，采用血清稳定性实验和体外释药、线粒体靶向性对该载药系统进行评价。结果 DLD/Hyp-Lip最佳处方为磷脂总量和金丝桃苷用量比为12.50：1，磷脂总量与胆固醇用量比为6.00：1，DSPE-PEG与DLD用量比为3：5；测得金丝桃苷包封率为（95.57±0.56）%，载药量为（8.55±0.57）%。所制备的DLD/Hyp-Lip外观良好，平均粒径为（124.9±3.4）nm，Zeta电位为（-6.2±1.9）mV；在胎牛血清中性状稳定，在体外释放介质中24 h累积释放量达到40%。线粒体靶向实验表明DLD/Hyp-Lip可以促进药物聚集在线粒体部位。结论 采用此方法能够精准有效的优化DLD/Hyp-Lip的制备工艺，该方法操作简单方便，可以用于DLD/Hyp-Lip制备与处方的优化，制备的DLD/Hyp-Lip包封率高，粒径小，分布均匀，且具有良好的缓释作用，为DLD/Hyp-Lip的进一步体内研究奠定了基础。载金丝桃苷的DLD/Hyp-Lip具有良好的肝癌细胞线粒体靶向性，是一种潜在高效的肝癌细胞线粒体靶向给药系统。     

Balancing Workload in the PACU by Using an Integrated OR Planning Methodology

PurposeThe individual scheduling of the operating rooms (ORs) has a significant influence on postoperative care at hospital facilities. We studied the effect of incorporating postoperative departments in the decision process with regard to scheduling ORs and developed an integrated OR planning methodology that determines an optimal surgery sequence and postanesthesia care unit (PACU) nursing staff level, with the objective to level the variability in inflow of patients in the PACU.DesignWe developed an integrated OR planning methodology that investigates the sequencing of a surgical suite process with multiple ORs and postoperative hospital facilities.MethodsThis research was performed by representing a discrete-time two-stage flow shop problem. A retrospective study was performed in which the derived model was validated using discrete-event simulation.FindingsSimulation results show that applying the integrated planning methodology decreased the variability in bed demand and smoothed the workload for the nursing staff in the PACU. Moreover, applying the algorithm led to a decrease in PACU completion time and a reduced amount of overtime hours for the surgical suite. Based on our results, we derived simple scheduling guidelines.ConclusionsOur simulation results confirmed the hypothesis that prospectively sequencing ORs' cases can effectively decrease the variability in bed demand and smoothen the workload for the staff personnel. Moreover, applying the algorithm leads to a decrease in PACU completion time and less overtime hours for the surgical suite. As such, an integrated OR planning methodology facilitates hospitals in improving OR efficiency.     

Avian mud nest architecture by self-secreted saliva

Mud nests built by swallows (Hirundinidae) and phoebes (Sayornis) are stable granular piles attached to cliffs, walls, or ceilings. Although these birds have been observed to mix saliva with incohesive mud granules, how such biopolymer solutions provide the nest with sufficient strength to support the weight of the residents as well as its own remains elusive. Here, we elucidate the mechanism of strong granular cohesion by the viscoelastic paste of bird saliva through a combination of theoretical analysis and experimental measurements in both natural and artificial nests. Our mathematical model considering the mechanics of mud nest construction allows us to explain the biological observation that all mud-nesting bird species should be lightweight.

Bird nests come in a variety of forms made from diverse building materials (1, 2). Each type of bird nest is subjected to mechanical constraints imposed by material characteristics. To overcome these constraints, birds have devised brilliant architectural technologies, which provide inspiration for a novel materials processing scheme and help us to better understand animal behavior.For instance, some birds including storks (Cicioniidae) and eagles (Accipitidae) build nests by piling up hard filamentary materials such as twigs, harnessing their friction as the cohesion mechanism (3). Weaverbirds (Ploceidae) weave soft filamentary materials such as grass and fine leaves into a woven nest tied to a tree branch. Some bird species use their own saliva in nest building, which Darwin considered an example of natural selection (4). An extreme case is the Edible-nest Swiftlets, which build their nest purely of self-secreted saliva so that it can be attached to cliff walls and cave ceilings where the above twig piles and tied leaves are not allowed (5).Swallows (Hirundinidae), phoebes (Sayornis), and other mud nesters have developed a unique building material, a mixture of mud and their own saliva, in contrast to those made of purely collected or self-secreted materials (6) (Fig. 1). During construction, mud nesters repeatedly pile a beakful of wet mud on the nest, and liquid bridges are formed in the nest due to evaporation. While building a nest usually takes several weeks, a transition from wet to dry structures can occur within a few hours. Hence, the capillary forces of liquid bridges temporarily provide cohesion such as those in sandcastles. However, unlike sandcastles, dehydrated saliva comes into play for permanent cohesion after complete evaporation (SI Appendix, Supplementary Note 1).Open in a separate windowFig. 1.A nest of the barn swallow (H. rustica). (A) Photograph of a barn swallow nest, taken from under the ceiling of a house in Suwon-si, Gyunggi-do, South Korea (37°16′13.5″N 126°59′01.0″E). (B) SEM image of the nest surface. (C) Chemical composition analysis of the surface shown in B by EDS. The red area indicates a region containing mostly carbon atoms, which may originate from bird saliva. The green area indicates a region containing mostly the silicon atoms of clay particles.Mud itself cannot confer sufficient cohesion and adhesion in mud nests. The ability of mud nests to bear tensile loads originates from the gluing agent in the bird''s saliva, which permeates into granules as a liquid and binds them as a solid after solvent evaporation (6–8) (SI Appendix, Supplementary Note 2). The gluing agent is called mucin, a family of large glycoproteins that are ubiquitous in animal organs and form a mucus gel with versatile functionality (9). Fig. 1B shows the scanning electron microscopy (SEM) image of a barn swallow’s mud nest consisting of platelet clay particles and larger grains. Energy-dispersive spectroscopy (EDS) mapping image of Fig. 1C clearly shows regions corresponding to organic material which is presumed to be from bird’s saliva.Of particular interest and worth biophysical investigation are the tensile strength of the mud nest with hardened saliva, design principles associated with the saliva-originated strength, and the resulting effects on the evolution of these mud-nesting birds. Principles behind cohesion in granular materials, such as wet sands (10), cemented powder aggregates (11), construction materials (12), and pharmaceutical tablets (13), have been studied to date, exploring the stress transmission, elasticity, and failure (14–18), and the formation of solidified bridges (19–21). However, little attention has been paid to the cohesion effects of self-secreted polymer materials upon evaporation and the biologically constructed granular architecture like birds’ mud nests. Here we devised experimental techniques to measure the strength of the relatively small and fragile nest specimens in order to mechanically characterize birds’ mud nests. We elucidate how solutes from bird saliva generate solid bridges that give rise to macroscopic tensile strength, which has long awaited physicochemical explanation since its first observation (4). To characterize the design principle of bird''s mud nests, we investigated natural and three-dimensional (3D)-printed artificial nests with various tools for visualization and mechanical testing. Along with the experimental studies, we theoretically investigated the effects of biopolymer concentration on nest strength. This combination of theory and experiment suggests that there is a size limit for mud-nesting birds, which is supported by biological data.     

A Computational Geometry Generation Method for Creating 3D Printed Composites and Porous Structures

A computational method for generating porous materials and composite structures was developed and implemented. The method is based on using 3D Voronoi cells to partition a defined space into segments. The topology of the segments can be controlled by controlling the Voronoi cell set. The geometries can be realized by additive manufacturing methods, and materials can be assigned to each segment. The geometries are generated and processed virtually. The macroscopic mechanical properties of the resulting structures can be tuned by controlling microstructural features. The method is implemented in generating porous and composite structures using polymer filaments i.e., polylactic acid (PLA), thermoplastic polyurethane (TPU) and nylon. The geometries are realized using commercially available double nozzle fusion deposition modelling (FDM) equipment. The compressive properties of the generated porous and composite configurations are tested quasi statically. The structures are either porous of a single material or composites of two materials that are geometrically intertwined. The method is used to produce and explore promising material combinations that could otherwise be difficult to mix. It is potentially applicable with a variety of additive manufacturing methods, size scales, and materials for a range of potential applications.     

Xenograft materials in maxillary sinus floor elevation surgery: a systematic review with network meta-analyses

A systematic review and network meta-analysis was conducted to compare different commercially available xenograft materials used in maxillary sinus floor elevation surgery (MSFES). Embase, PubMed, the Cochrane Library, Web of Science, Scopus, LILACS, and grey literature were searched up to 13 July 2020. Only randomised controlled trials (RCTs) were included. A frequentist network meta-analysis using a random effects model compared different commercially available xenograft materials. The primary outcomes were the percentage of newly-formed bone and residual bone-substitute rate. Both were measured by histomorphometric analysis from bone biopsies obtained during preparation of the implant site. Of the 659 studies initially identified, 11 involving 242 MSFES were included in the quantitative analyses. A total of six bone-substitute materials were analysed (Bio-Oss® (Geistlich Pharma), InduCera® Dual Coat, Lumina-Bone Porous® (Critéria), Osseous® (SIN - Sistema de Implantes Nacional), THE Graft® (Purgo Biologics), and Osteoplant Osteoxenon® (Bioteck)). The P-score estimation showed that Osteoplant Osteoxenon® produced the most newly-formed bone and reabsorbed faster than other xenograft materials after six months. The combination of Bio-Oss® plus bone marrow aspirate concentrate (BMAC) significantly increased the percentage of newly-formed bone compared with Bio-Oss® alone. In contrast, the addition of Emdogain® (Straumann) and leucocyte and platelet-rich fibrin (L-PRF) to Bio-Oss® did not significantly improve the amount of regenerated bone. Study-level data indicated that the percentage of newly-formed bone differs among commercially available xenograft materials. Osteoplant Osteoxenon® seems to result in the highest amount of new bone in MSFES.     

几何不确定性鲁棒优化在肝癌立体定向放疗中的应用

目的:分析基于几何不确定性的鲁棒优化计划对肝癌立体定向放疗（SBRT）剂量分布的影响。方法:选取12例肝癌SBRT患者，对每例制作3个调强计划:①基于PTV（ITV-PTV 5 mm）的常规优化（PTV-Based Plan）；②基于ITV非均匀几何不确定性（本中心计算的不确定性值:进出方向7 mm，左右和前后方向4 mm）的鲁棒优化（Robust Planactual）；③基于ITV均匀5 mm几何不确定性的鲁棒优化（Robust Plan5 mm）。所有计划都以95%的PTV满足处方剂量作为目标，以等中心均匀偏移4、5、7 mm计算扰动剂量评估鲁棒性。结果:计划①②③的均匀性指数（HI）分别为0.083±0.027、0.099±0.035、0.096±0.026，不具有统计学意义；计划①②③的适形性指数（CI）分别为0.98±0.02、1.02±0.05、1.00±0.04，计划②③相对于计划①的CI具有统计学意义。计划③的正常肝组织平均受量和V2500相对于计划①②分别下降了4.1%、2.5%和5.4%、3.0%，且具有统计学意义（P=0.034、P=0.021和P=0.004、P=0.004），计划②相对于计划①的正常肝组织平均受量和V2500不具有统计学意义（P=0.308和P=0.182），但下降了1.6%和2.5%。对于其鲁棒性，计划②③的5 mm-D99%、5 mm-D98%、5 mm-D95%的剂量-体积直方图带宽（DVHBW）差值相对于计划①更小，随着摆位不确定度的增大，其DVHBW差值越大。结论:在肝脏SBRT治疗中，采用鲁棒优化能够提高靶区剂量分布质量，即使在摆位不确定度有所增加的情况下，仍可以保证ITV的剂量覆盖同时不增加正常组织的照射剂量。     

Assisted Peritoneal Dialysis for Older People with End-Stage Renal Disease: The French and Danish Experience

Older people are the largest and fastest growing group of patients with end-stage renal disease (ESRD), and, due to advanced age and a heavy burden of comorbidities, they are usually not candidates for renal transplantation or home-based dialysis treatment. Some of the barriers for home treatment are non-modifiable, but the majority of physical disabilities and psychosocial problems can be overcome provided that assistance is offered to the patients at home.In the present review, we describe the programs for assisted peritoneal dialysis (PD) in France and Denmark, respectively. In both nations, assisted PD is totally publicly funded, and the cost of assisted PD is comparable to the cost of in-center HD. Assisted continuous ambulatory PD (aCAPD) is the preferred modality in France whereas assisted automated PD (aAPD) is the preferred modality in Denmark. Assistants are professional nurses or healthcare technicians briefly educated by expert PD nurses from the dialysis unit.The establishment of a program for assisted PD may increase the number of patients actually treated with PD and may reduce the risk of PD technique failure and prolong PD duration. Compared with autonomous PD patients, patients on assisted PD may have shorter patient survival and peritonitis-free survival indicating that, besides advanced age and the burden of comorbidities, dependency on help may be an independent risk factor for poorer outcome.Assisted PD is an evolving dialysis modality, and may in the future prove to be a feasible complementary alternative to in-center hemodialysis (HD) for the growing group of dependent older patients with ESRD.