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 BLAN_mCas9/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.

Objective:To investigate the predictive value of serum levels of tribbles pseudokinase 3(TRIB3)and storkhead box 1(STOX1)for prognosis in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 116 CHD patients undergoing PCI in Daye People's Hospital between May 2019 and August 2022 were enrolled as CHD group,another 95 healthy volunteers undergoing physical examination in our hospital simultaneously were selected as control group.According to presence of major adverse cardiovascular events(MACE)within 3 months after PCI,CHD group was divided into MACE group(n=21)and no MACE group(n=95).Enzyme-linked immunosorbent assay(ELISA)was used to measure serum TRIB3 and STOX1 levels;multivariate Logistic regression was used to analyze influencing factors of poor prognosis in CHD patients after PCI;receiver operating characteristic(ROC)curve was used to analyze predictive value of serum TRIB3 and STOX1 for poor prognosis in CHD patients after PCI.Results:Compared with participants in control group,those in CHD group had significant higher serum TRIB3 and STOX1 levels(P＜0.001 all).Compared with participants in no MACE group,those in MACE group had significant higher serum levels of TRIB3[(9.65±1.27)ng/ml vs.(12.04±1.64)ng/ml]and STOX1[(16.06±1.54)ng/ml vs.(18.21±1.78)ng/ml](P＜0.001 all).Multivariate Lo-gistic regression showed that serum TRIB3 and STOX1 levels were independent risk factors for MACE in CHD pa-tients after PCI(OR=3.859,2.159,P＜0.001 both).ROC analysis indicated that combined detection of serum TRIB3 and STOX1(area under the curve(AUC)=0.916)had higher predictive value for poor prognosis in CHD patients after PCI compared to those of single detection(AUC=0.837,0.776).Conclusion:Serum levels of TRIB3 and STOX1 significantly increase in CHD patients after PCI suffering from MACE,and the combination of both can better predict the prognosis of these patients.

Objective:To investigate the predictive value of serum levels of tribbles pseudokinase 3(TRIB3)and storkhead box 1(STOX1)for prognosis in patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:A total of 116 CHD patients undergoing PCI in Daye People's Hospital between May 2019 and August 2022 were enrolled as CHD group,another 95 healthy volunteers undergoing physical examination in our hospital simultaneously were selected as control group.According to presence of major adverse cardiovascular events(MACE)within 3 months after PCI,CHD group was divided into MACE group(n=21)and no MACE group(n=95).Enzyme-linked immunosorbent assay(ELISA)was used to measure serum TRIB3 and STOX1 levels;multivariate Logistic regression was used to analyze influencing factors of poor prognosis in CHD patients after PCI;receiver operating characteristic(ROC)curve was used to analyze predictive value of serum TRIB3 and STOX1 for poor prognosis in CHD patients after PCI.Results:Compared with participants in control group,those in CHD group had significant higher serum TRIB3 and STOX1 levels(P＜0.001 all).Compared with participants in no MACE group,those in MACE group had significant higher serum levels of TRIB3[(9.65±1.27)ng/ml vs.(12.04±1.64)ng/ml]and STOX1[(16.06±1.54)ng/ml vs.(18.21±1.78)ng/ml](P＜0.001 all).Multivariate Lo-gistic regression showed that serum TRIB3 and STOX1 levels were independent risk factors for MACE in CHD pa-tients after PCI(OR=3.859,2.159,P＜0.001 both).ROC analysis indicated that combined detection of serum TRIB3 and STOX1(area under the curve(AUC)=0.916)had higher predictive value for poor prognosis in CHD patients after PCI compared to those of single detection(AUC=0.837,0.776).Conclusion:Serum levels of TRIB3 and STOX1 significantly increase in CHD patients after PCI suffering from MACE,and the combination of both can better predict the prognosis of these patients.

Objective: To investigate the clinical presentation and genetic characteristics of malignant infantile osteopetrosis. Methods: This was a retrospective case study. Thirty-seven children with malignant infantile osteopetrosis admitted into Beijing Children's Hospital from January 2013 to September 2022 were enrolled in this study. According to the gene mutations, the patients were divided into the CLCN7 group and the TCIRG1 group. Clinical characteristics, laboratory tests, and prognosis were compared between two groups. Wilcoxon test or Fisher exact test were used in inter-group comparison. The survival rate was estimated with the Kaplan-Meier method and the Log-Rank test was used to compare the difference in survival between groups. Results: Among the 37 cases, there were 22 males and 15 females. The age of diagnosis was 0.5 (0.2, 1.0) year. There were 13 patients (35%) and 24 patients (65%) with mutations in CLCN7 and TCIRGI gene respectively. Patients in the CLCN7 group had an older age of diagnosis than those in the TCIRGI group (1.2 (0.4, 3.6) vs. 0.4 (0.2, 0.6) years, Z=-2.60, P=0.008). The levels of serum phosphorus (1.7 (1.3, 1.8) vs. 1.1 (0.8, 1.6) mmol/L, Z=-2.59, P=0.010), creatine kinase isoenzyme (CK-MB) (457 (143, 610) vs. 56 (37, 82) U/L, Z=-3.38, P=0.001) and the level of neutrophils (14.0 (9.9, 18.1) vs. 9.2 (6.7, 11.1) ×10⁹/L, Z=-2.07, P=0.039) at diagnosis were higher in the CLCN7 group than that in the TCIRG1 group. However, the level of D-dimer in the CLCN7 group was lower than that in the TCIRGI group (2.7 (1.0, 3.1) vs. 6.3 (2.5, 9.7) μg/L, Z=2.83, P=0.005). After hematopoietic stem cell transplantation, there was no significant difference in 5-year overall survival rate between the two groups (92.3%±7.4% vs. 83.3%±7.6%, χ²=0.56, P=0.456). Conclusions: TCIRGI gene mutations are more common in children with osteopetrosis. Children with TCIRGI gene mutations have younger age, lower levels of phosphorus, CK-MB, and neutrophils and higher level of D-dimer at the onset. After hematopoietic stem cell transplantation, patients with CLCN7 or TCIRGI gene mutations have similar prognosis.
Child ; Male ; Female ; Humans ; Osteopetrosis/therapy* ; Retrospective Studies ; Prognosis ; Genes, Recessive ; Phosphorus ; Chloride Channels/genetics* ; Vacuolar Proton-Translocating ATPases/genetics*

Background Ultrasound-guided continuous thoracic paravertebral block can provide pain-relieving and opioid-sparing effects in patients receiving open hepatectomy. We hypothesize that these effects may improve the quality of recovery (QoR) after open hepatectomy. Methods Seventy-six patients undergoing open hepatectomy were randomized to receive a continuous thoracic paravertebral block with ropivacaine (CTPVB group) or normal saline (control group). All patients received patient-controlled intravenous analgesia with morphine postoperatively for 48 hours. The primary outcome was the global Chinese 15-item Quality of Recovery score on postoperative day 7, which was statistically analyzed using Student's t-test. Results Thirty-six patients in the CTPVB group and 37 in the control group completed the study. Compared to the control group, the CTPVB group had significantly increased global Chinese 15-item Quality of Recovery scores (133.14 ± 12.97 vs. 122.62 ± 14.89, P = 0.002) on postoperative day 7. Postoperative pain scores and cumulative morphine consumption were significantly lower for up to 8 and 48 hours (P < 0.05; P = 0.002), respectively, in the CTPVB group. Conclusion Perioperative CTPVB markably promotes patient's QoR after open hepatectomy with a profound analgesic effect in the early postoperative period.
Anesthetics, Local/therapeutic use* ; Double-Blind Method ; Hepatectomy/adverse effects* ; Humans ; Morphine/therapeutic use* ; Pain Measurement ; Pain, Postoperative/etiology* ; Ultrasonography, Interventional

Background::Mounting evidence, consistent with our previous study, showed that γ-aminobutyric acid type A receptor (GABAAR) played an indispensable role in airway inflammation and mucus hypersecretion in asthma. Monocyte chemotactic protein-inducing protein 1 (MCPIP1) was a key negative regulator of inflammation. Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases. However, the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied. This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells, and its potential mechanism.Methods::In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were chosen. Interleukin (IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells. MCPIP1 Lentiviral vector (LA-MCPIP1) and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells, respectively. MCP-1, thymic stromal lymphopoietin (TSLP), mucin 5AC (MUC5AC), MCPIP1, and GABAARβ2 expressions were measured in both lung and BEAS-2B cells. Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells. Results::MCPIP1 was up-regulated by LA-MCPIP1 ( P < 0.001) and plasmid-MCPIP1 ( P < 0.001) in lung and cells, respectively. OVA-induced airway inflammation and mucus hypersecretion, OVA-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice (all P < 0.001). IL-13-enhanced MCP-1, TSLP, MUC5AC, and GABAARβ2 expressions, and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells (all P < 0.001). Conclusion::The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells, involving GABAAR signaling pathway.

China ; Humans ; Otolaryngology

Head and Neck Neoplasms ; Humans ; Randomized Controlled Trials as Topic

OBJECTIVE: To study the association between IL-10 gene-592(C→A) (rs1800872) single nucleotide polymorphism (SNP) and the graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: Ninety-seven childhood patients and seventy-one donors in the Hematology Oncology Center of Beijing Children's Hospital from Jan 2011 to Jul 2017 were enrolled in this study. The genomic DNA was extracted from peripheral blood cells and the SNP genotype was analyzed using TaqMan SNP genotyping assay. RESULTS: In malignant patients with AA genotype, the incidence of Ⅱ-Ⅳ grade acute GVHD (aGVHD) was lower than that in patients with AC and CC genotype (9.1% vs 43.5%) (P＜0.01), and the gastrointestinal aGVHD rate was also lower (9.1% vs 39.1%) (P＜0.05). There's no significant association between patients' genotype and Ⅱ-Ⅳ grade aGVHD in total patients and non-malignant patients. Also, the genotype in patients did not corelate with chronic GVHD (cGVHD) and 1 year transplantation-related mortality (TRM). In cases who received HSCT of donors with AA genotype, the liver aGVHD rate was higher than that in cases who received HSCT of donors with AC and CC genotype (23.1% vs 0.0%) (P＜0.05), but the genotype in donors did not correlate with Ⅱ-Ⅳ grade aGVHD, cGVHD and 1 year TRM. CONCLUSION AA genotype in the IL-10 gene-592 (C→A) (rs1800872) single nucleotide polymorphism in patients protects pediatric malignant patients against Ⅱ-Ⅳ grade aGVHD and gastrointestinal aGVHD after allo-HSCT. AA genotype in donors is a risk factor for liver aGVHD after allo-HSCT in non-malignant disease.
Child ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Interleukin-10 ; genetics ; Polymorphism, Single Nucleotide ; Tissue Donors