1.Optimized lipid nanoparticles enable effective CRISPR/Cas9-mediated gene editing in dendritic cells for enhanced immunotherapy.
Kuirong MAO ; Huizhu TAN ; Xiuxiu CONG ; Ji LIU ; Yanbao XIN ; Jialiang WANG ; Meng GUAN ; Jiaxuan LI ; Ge ZHU ; Xiandi MENG ; Guojiao LIN ; Haorui WANG ; Jing HAN ; Ming WANG ; Yong-Guang YANG ; Tianmeng SUN
Acta Pharmaceutica Sinica B 2025;15(1):642-656
Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLANmCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.
2.The application value of paediatric age-adjusted shock index in children with sepsis and septic shock
Wei LI ; Haiyan GE ; Shuang LIU ; Siyuan HUANG ; Jing CHEN ; Ning LI ; Xiuxiu LU ; Dong QU
Chinese Pediatric Emergency Medicine 2025;32(7):500-503
Objective:To explore the value of paediatric age-adjusted shock index(SIPA)in early identification of septic shock in children,and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased,they were divided into two groups:compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed,and the predictive value of SIPA on case fatality rate,lactate level,pediatric critical illness score,ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis,112 were males and 91 were females. There were 146 cases in the sepsis group,37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender( P>0.05),but there was a statistically significant difference in age( χ 2=32.905, P<0.001). There was no significant difference in age between the sepsis group and the compensated septic shock group( P>0.05). The age of sepsis group and decompensated septic shock group,compensated septic shock group and decompensated septic shock group were statistically significant( χ 2=29.431, P<0.001; χ 2=19.764, P=0.001). The proportion of increased SIPA was statistically different among the three groups,with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group( χ2=20.383, P<0.001; χ2=33.600, P<0.001). The decompensated septic shock group was higher than the compensated septic shock group( χ2=6.555, P=0.01). SIPA was correlated with case fatality rate,lactate level,pediatric critical illness score,ventilator use rate and length of stay of the children,with statistically significant differences( P<0.05). Conclusion:The increase of SIPA can be used for the early identification of septic shock in children,and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.
3.The application value of paediatric age-adjusted shock index in children with sepsis and septic shock
Wei LI ; Haiyan GE ; Shuang LIU ; Siyuan HUANG ; Jing CHEN ; Ning LI ; Xiuxiu LU ; Dong QU
Chinese Pediatric Emergency Medicine 2025;32(7):500-503
Objective:To explore the value of paediatric age-adjusted shock index(SIPA)in early identification of septic shock in children,and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased,they were divided into two groups:compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed,and the predictive value of SIPA on case fatality rate,lactate level,pediatric critical illness score,ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis,112 were males and 91 were females. There were 146 cases in the sepsis group,37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender( P>0.05),but there was a statistically significant difference in age( χ 2=32.905, P<0.001). There was no significant difference in age between the sepsis group and the compensated septic shock group( P>0.05). The age of sepsis group and decompensated septic shock group,compensated septic shock group and decompensated septic shock group were statistically significant( χ 2=29.431, P<0.001; χ 2=19.764, P=0.001). The proportion of increased SIPA was statistically different among the three groups,with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group( χ2=20.383, P<0.001; χ2=33.600, P<0.001). The decompensated septic shock group was higher than the compensated septic shock group( χ2=6.555, P=0.01). SIPA was correlated with case fatality rate,lactate level,pediatric critical illness score,ventilator use rate and length of stay of the children,with statistically significant differences( P<0.05). Conclusion:The increase of SIPA can be used for the early identification of septic shock in children,and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.
4.Determination of Phosphates, Tetrabromobisphenol A and Sudan Ⅰ in Children Products by Ultra Performance Liquid Chromatography-Mass Spectrometry
Ying LAI ; Rui LIN ; Weijing LIN ; Xiuxiu GE ; Qingmu DONG ; Bin LI ; Huajun DING ; Haixia LIN ; Xingpeng TU ; Xiaoling CHEN ; Shuai YE
Chinese Journal of Analytical Chemistry 2016;(8):1236-1242
A reliable UPLC-MS method was developed for the simultaneous determination of 4 chemicals (Sudan Ⅰ, tetrabromobisphenol A, tris ( 1, 3-dichloroisopropyl ) phosphate and tris ( chlorisopropyl ) Phosphate) in children products. The samples were ultrasonic extracted with acetonitrile, and then the four chemicals were separated on a C18 column in 3 min. Results showed that the limit of quantification of the method was between 5 and 500μg/kg. The calibration curves were linear within 2-3 orders of magnitude with typical correlation coefficient above 0 . 9995 . The recoveries ranged from 83 . 7% to 97 . 8% with three addition levels. The sensitivity, recovery and selectivity of the method could fully meet the requirements of practical work.
5.Function and mechanism of PAR6 gene in the occurrence and development of tumor
Xiuxiu HOU ; Zhiqiang LING ; Minghua GE
Journal of International Oncology 2015;(5):347-350
Cell polarity is a common feature of many different types of cells,and it is essential to the normal differentiation and function of cells. Partitioning defective 6( PAR6)gene encodes PAR6 protein, which is crucial to asymmetric cell division and polarized growth. PAR6 protein as a member of the PAR6 polarity complex,affects the synthetic of centrosome and protein recruitment to the centrosome. The abnormal number of centrosomal and the loss of cell polarity may eventually lead to the occurrence of tumor.
6.Post-operation TSH suppression therapy in differentiated thyroid carcinoma
Journal of International Oncology 2014;(8):585-588
Surgical operation is still the main means of thyroid carcinoma,especially the differentiated thyroid carcinoma. Postoperative endocrine therapy is considered as an important adjuvant therapy. Giving the corresponding endocrine therapy after the surgery,not only prevent the hypothyroidism,but also reduce the recurrence rate and mortality in postoperative patients with thyroid carcinoma.

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