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.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
3.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
4.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
5.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
6.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
7.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
8.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
9.Association of alcohol consumption with aortic aneurysm and dissection risk:results from the UK Biobank cohort study
Liang YAOWEN ; Zou GUOXIANG ; Wang DINGCHEN ; Zeng WEIYUE ; Zhang JIARUI ; Huang XIAORAN ; Lin MIAO ; Mai CONG ; Song FEI'ER ; Zhang YUELIN ; Meng JINXIU ; Feng HONGLIANG ; Huang YU ; Li XIN
World Journal of Emergency Medicine 2024;15(6):465-474
BACKGROUND:Previous studies have reported inconsistent results with positive,negative,and J-shaped associations between alcohol consumption and the hazard of aortic aneurysm and dissection(AAD).This study aimed to examine the connections between weekly alcohol consumption and the subsequent risk of AAD. METHODS:The UK Biobank study is a population-based cohort study.Weekly alcohol consumption was assessed using self-reported questionnaires and the congenital risk of alcohol consumption was also evaluated using genetic risk score(GRS).Cox proportional hazards models were used to estimate hazard ratios(HRs)with 95%confidence intervals(CIs)for the associations between alcohol consumption and AAD.Several sensitivity analyses were performed to assess the robustness of the results. RESULTS:Among the 388,955 participants(mean age:57.1 years,47.4%male),2,895 incident AAD cases were documented during a median follow-up of 12.5 years.Compared with never-drinkers,moderate drinkers(adjusted HR:0.797,95%CI:0.646-0.984,P<0.05)and moderate-heavy drinkers(adjusted HR:0.794,95%CI:0.635-0.992,P<0.05)were significantly associated with a decreased risk of incident AAD.Interaction-based subgroup analysis revealed that the protective effect of moderate drinking was reflected mainly in participants younger than 65 years and women. CONCLUSION:Our findings support a protective effect of moderate alcohol consumption on AAD,but are limited to participants younger than 65 years and women.
10.Preliminary application of robot-assisted core-needle biopsy for the bone tumors
Yu CHEN ; Libin XU ; Xiaotong MENG ; Lin CONG ; Yue ZHU
Chinese Journal of Postgraduates of Medicine 2024;47(10):870-874
Objective:To assess the usage of the robot-assisted core-needle biopsy for the bone tumors, moreover to compare its outcomes with the manual technique.Methods:A retrospective study was conducted from February 2019 to February 2021, the medical records of the patients with bone lesions that had received core-needle biopsy were collected. There were 57 males and 45 females, the age was 45.9 (10~79) years. Eight patients received robot-assisted biopsy, whereas 94 patients underwent C-arm/ CT guided biopsy, the recorded data included operational duration, aspirational direction adjustment, etc. The pathological diagnosis reports of the biopsy specimens and the operational specimens were compared.Results:The diagnosis outcomes included metastases (33 cases), osteosarcoma (12 cases), chondrosarcoma (12 cases), giant cell tumor of bone (12 cases), fibrous dysplasia (7 cases), chronic osteomyelitis (7 cases), lymphoma (4 cases), multiple myeloma (4 cases), chronic fracture (3 cases), chondroblastoma (2 cases), pleomorphic undifferentiated sarcoma (2 cases), leiomyosarcoma (1 case), and Langerhans cell histiocytosis (1 case). Eighty-seven cases (85.29 %) lesions were found in the limbs, whereas 15 cases (14.71%) were in the axial locations. Compared with the manual group, the robot-assisted group had more axial locations: 7/8 vs. 11.70%(11/94), P<0.01; fewer aspirational direction adjustment: (0.4 ± 0.1) times vs. (3.1 ± 1.5) times, P<0.01 ; longer operational duration: (48.8 ± 8.8) min vs. (29.6 ± 6.0) min, P<0.01. There were no statistical differences between the two groups regarding the sex, age, pathological fracture, diagnostic accuracy, open biopsy rate and complications ( P>0.05). Conclusions:The robot-assisted core-needle biopsy is a reliable technique, it helps decrease the operational difficulty. The usage of this technique is recommendable for the bone lesions with great difficulty for biopsy, such as the minimal bone tumors and the lesions in the spine and the pelvis.

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