Pre-existing anti-polyethylene glycol (PEG) antibodies represent risk factors for reduced efficacy and increased adverse reactions in seropositive individuals, but neither the seropositivities, nor levels nor influencing factors have been investigated in pregnant women or newborns. Herein, maternal and cord blood samples were respectively collected from 256 pregnant women and corresponding 256 newborns at the Women's Hospital, Zhejiang University School of Medicine in China for further determination of pre-existing anti-PEG antibodies, along with questionnaire interviews, demographic and clinical data collections. Our data showed that the seropositivities of total anti-PEG antibodies, anti-PEG IgG1 and IgG2, anti-PEG IgM, and coexistence of anti-PEG IgM and IgG were 19.14%, 2.34%, 7.03%, 10.94% and 1.17%, respectively, in pregnant women, and 5.47%, 2.73%, 2.73%, 0% and 0%, respectively, in newborns. Anti-PEG IgG3, IgG4 and IgE were undetectable in all blood samples. Median anti-PEG IgG1, IgG2 and IgM concentrations were 273.88 ng/mL, 748.35 ng/mL and 175.07 ng/mL, respectively, in pregnant women. Median anti-PEG IgG1 and IgG2 concentrations were 207.92 ng/mL and 336.52 ng/mL, respectively, in newborns. Interestingly, in-depth statistical analyses revealed that maternal age, take-out food consumption and cosmetic use were influencing factors of maternal anti-PEG antibodies, while newborn anti-PEG antibodies were affected by maternal age and cosmetic use. These seroepidemiological characteristics raise concerns over the clinical use of PEGylated drugs in pregnant women and newborns, and provide valuable insight into the induction of risky pre-existing anti-PEG antibodies.

Little is known about how cell cycle and autophagy, two fundamental life processes, affect cellular accumulation of nanoparticles. What's even more tough is that several long-lasting methodological barriers have hindered the progress of related research. Here we firstly show the construction of a multi-functional platform for overcoming existing methodological obstacles through integrating multiple technical approaches including autophagy-related gene 7 knockout to specifically block autophagy, PIP-FUCCI transfection and mitotic shake-off to thoroughly separate cell cycle phases, and 3D reconstruction to stereoscopically evaluate cellular accumulation of nanoparticles. Further application of this platform reveals that after a 2-hour incubation of lipid-based nanoparticles, G2-phase and M-phase cells, two populations previously muddled up together as G2/M-phase cells, respectively exhibited the maximum and minimum nanoparticle accumulation. Meanwhile, our data preliminarily suggest enhanced nanoparticle accumulation by autophagy blockade. Besides cell cycle and autophagy, comprehensive statistical analyses reveal a close association between cellular accumulation of nanoparticles and nanoparticle type. This study not only provides a valuable technical strategy, but uncovers important characteristics of cellular accumulation of nanoparticles, offering new insights for optimization and application of nanomedicines.

Cellular uptake of biomedical nanoparticles has been shown to be affected by key cellular biological properties. However, very little is known about the influence of cell cycle and autophagy on nanoparticle uptake. What’s even more tough is that several long-lasting methodological barriers hamper the experimental performance and restrict the research and development. Herein, a multi-functional platform was initially constructed for simultaneously overcoming existing obstacles by integrating several technical approaches, particularly mitotic shake-off, for complete and thorough cell cycle phase separation. Strikingly, further application of this platform revealed that G2-phase and M-phase cells, two cell populations previously muddled up together as G2/M-phase cells, respectively exhibited the maximum and minimum uptake of lipid-based nanoparticles. Moreover, our data generally provided a novel line of evidence for enhanced nanoparticle uptake by specific autophagy blockade. The cell cycle- and autophagy-associated characteristics of nanoparticle uptake discovered here offer new insights for optimization and application of nanomedicines.### Competing Interest StatementThe authors have declared no competing interest.

With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.

目的 分析国内外压力性损伤支撑面研究领域的热点及趋势,为未来相关研究提供参考.方法 检索Web of Science核心数据库、中国知网、万方数据库、维普网中收录的压力性损伤支撑面的相关文献,检索时限为2010年1月1日—2023年2月28日,应用CiteSpace软件进行可视化分析.结果 最终纳入中文文献307篇、英文文献434篇.美国是发文量最多的国家;南京军区南京总医院是国内发文量最多的机构;《中华现代护理杂志》是国内发文量最多期刊,Journal of Tissue Viability是国外发文量最多期刊;蒋琪霞是发文量最多的作者,Gefen是国外发文量最多的作者.中文文献共形成12个聚类,英文文献共形成17个聚类,最终各总结出8个有意义的类别(人群、部位、研究类型、危险因素、静态支撑面、动态支撑面、智能监测、效果评价),其中智能监测是未来研究的趋势.结论 压力性损伤支撑面是近年来国内外的研究热点,建议通过拓宽研究的应用人群范围、联合计算机和人工智能等学科研发利于推广的智能支撑面设备、开展大样本的高质量原始研究和相应的质量改进项目等方法推动国内压力性损伤预防护理研究的发展.

Objective:A foot cleaning device for bedridden patients in ICU was made, and its application effects in foot cleaning for bedridden patients in ICU was discussed.Methods:A total of 200 inpatients in the department of ICU from April 2021 to October 2021 were selected as the research objects.According to the random number table, the patients were divided into two groups, including 100 patients in the control group and 100 patients in the experimental group.The patients in the control group used an ordinary foot basin and dipped warm water by a towel for foot wiping and cleaning. The patients in the experimental group used a foot cleaning device for bedridden patients developed and designed by our hospital. Both groups received warm water foot bath for 20 minutes after cleaning. The incidence of adverse events, average foot washing time, total foot washing time, the subjective comfort and satisfaction of the patients and the satisfaction of the operator were observed.Results:The incidence of adverse events during foot cleaning in the experimental group was 2.00%(28/1 400) lower than 4.36%(61/1 400) in the control group, the difference was statistically significant ( χ2=11.88, P<0.05). The foot washing time in the observation group [(27.77 ± 1.34) min] was longer than that in the control group [(24.63 ± 2.36) min], the difference was statistically significant ( t=9.30, P<0.05). The total foot washing time in the observation group [(27.77 ± 1.34) min] was shorter than that in the control group [(49.26 ± 4.71)min], the difference was statistically significant ( t=42.51, P<0.05). The subjective comfort of foot cleaning, the satisfaction of foot cleaning of patients and the satisfaction of foot cleaning operators in the experimental group were 91.00 (91/100) , 97.00% (97/100) , 91.67% (55/60) , while the control group were 75.00% (75/100) 、85.00% (85/100) , 75.00% (45/60) , and the differences between the two groups were statistically significant ( Z=-3.04, -4.82, -2.71, all P<0.05). Conclusions:The self made foot cleaning device for bedridden patients in this study can be used in ICU patients. It can effectively reduce the incidence of adverse events in the process of foot washing and shorten the time of foot washing. It can also improve the comfort and satisfaction of patients, and improve the satisfaction of operators.

OBJECTIVE To explore the characteristics of intestinal microecology in hepatocellular carcinoma (HCC) model mice. METHODS C57BL/6 male mice aged 2 weeks were divided into normal control group and HCC model group. Mice in HCC model group were exposed to a single intraperitoneal injection of diethylnitrosamine (DEN) 2 weeks after birth; the surviving mice were intraperitoneally injected with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), once every 2 weeks for 8 times starting from the 4 th week after birth. Mice in each group were randomly selected and sacrificed at 10 th, 18 th and 32 nd weeks after birth, respectively, the liver tissue samples were obtained for histopathological examination. At the 32 nd week, all mice in both groups were sacrificed and the feces samples were collected under sterile conditions right before the sacrifice. The feces samples were sequenced for the V3-V4 hypervariable regions of the 16S rRNA gene, and the species abundance, flora diversity and phenotype, as well as flora correlation and functional prediction were analyzed. RESULTS Alpha diversity analysis showed that all Good's coverage reached the maximum value of 1.00, and the differences in the Observed features, Chao1 index, Shannon index and Simpson index of the intestinal flora of mice between normal control group and HCC model group were all statistically significant (all P<0.05). Beta diversity analysis showed that PCoA based on weighted or unweighted Unifrac distances all yielded R>0, confirming that the intra-group differences of the samples were less than the inter-group differences; the trend of separation between the two groups was significant ( P<0.05). Bacteroidetes, Firmicutes, Actinobacteria and Patescibacteria were the dominant taxa at the phylum level in both normal control group and HCC model group. However, compared with normal control group, the abundance of Bacteroidetes in HCC model group was significantly decreased ( P<0.01), while the abundance of Patescibacteria was significantly increased ( P<0.05). Moreover, the dominant taxa at the genus level in normal control group mainly included Muribaculaceae_unclassified, Paramuribaculum, Muribaculum, Lachnospiraceae_NK4A 136 group, Olsenella. The dominant taxa at the genus level in HCC model group mainly included Akkermansia, Dubosiella, Muribaculaceae_unclassified, Lachnospiraceae_NK4A 136 group, Coriobacteriaceae_UCG-002. There were 30 genera with statistically significant differences in relative abundance at the genus level between the two groups (all P<0.05). LEfSe analysis of the intestinal flora of mice in the two groups revealed a total of 14 multi-level differential taxa (all P<0.05, LDA score>4.0), which were mainly enriched in Bacteroidetes. The enrichment of 10 differential taxa including Bacteroidetes, Bacteroidia, Bacteroidales, Muribaculaceae, etc. were found in normal control group, and the enrichment of 4 differential taxa including Dubosiella, Peptostreptococus, etc. were found in HCC model group. There were both positive and negative correlations between the dominant intestinal genera in normal control group (|rho|>0.5, P<0.05), while the correlations of the dominant intestinal genera in HCC model group, being less complex than that in normal control group, were all positive. The relative abundance of gram positive and mobile element containing in the intestinal flora of mice in HCC model group was significantly up-regulated compared with normal control group (both P<0.05), while that of gram negative ( P<0.05) and pathogenic potential ( P<0.05) was significantly down-regulated. The metabolic pathways of the intestinal flora in the two groups were significantly different. For instance, 18 metabolic pathways were enriched in normal control group (all P<0.005), including those related to energy metabolism, cell division, nucleotide metabolism, etc., while 12 metabolic pathways were enriched in HCC model group (all P<0.005), including those related to energy metabolism, amino acid metabolism, carbohydrate metabolism, etc. Conclusions: The amount of intestinal flora in DEN-induced primary HCC model mice decreased, and the composition, correlation, phenotype and function of the intestinal flora in mice were significantly altered. Bacteroidetes at the phylum level, as well as several microbial taxa at the genus level such as Muribaculaceae_unclassified, Muribaculum, Peptostreptococus and Dubosiella could be closely associated with DEN-induced primary HCC in mice.