Objective To investigate the level 4 surgical safety management in tertiary public hospitals in Sichuan Province.Methods A combination of questionnaires and qualitative interviews was used to investigate the basic situation of four-level surgery performed,the volume of surgery,and the management of surgery in 34 tertiary public hospitals in Sichuan Province.Results Among the 34 tertiary public hospitals surveyed,the percentage of patients discharged with level Ⅳ surgery in 2023 was 18.96％,which was lower than the level of the percentage of patients discharged with level Ⅳ surgery did not establish a leading group for level Ⅳ surgery (17.65％),a system for preoperative multidisciplinary discussion of level Ⅳ surgery(14.71％),and a system for preoperative multidisciplinary discussion of level Ⅳ surgery with various department-related expert pool(41.18％),multidisciplinary joint examination room(23.53％),and the monitoring and evaluation mechanism for the completion of preoperative multidisciplinary discussion for level 4 surgery(20.59％).Conclusion The volume of level Ⅳ surgeries in tertiary public hospitals in Sichuan Province needs to continue to be improved,and the establishment of a standardized management system for level Ⅳ surgeries is imperative.

OBJECTIVE To investigate the biodistribution of lipid nanoparticles(LNPs)with different surface charges and different particle sizes in mice.METHODS LNPs were prepared using microfluidic technology by incorporating positively charged phospholipids,negatively charged phospholipids,ioniz-able phospholipids,and neutral phospholipids into the formulation to create LNPs with corresponding surface charges.The particle size of the LNPs was controlled by polyethylene glycol(PEG)modifica-tion and measured using dynamic light scattering(DLS)and transmission electron microscopy(TEM),while the surface charge was analyzed using a zeta potential analyzer.The LNPs were labeled with a fluorescent dye,and the mice were intravenously injected with 0.625 μmol·kg-1 of LNPs.At 1,4,12 and 24 h post-injection,the brain,heart,livers,spleen,lungs and kidneys were collected.The fluorescence distribution in different organs was detected using an in vivo imaging system to reflect the distribution of LNPs in various organs.RESULTS Particle size analysis showed that,except the ionizable lipid nanoparticles without PEG modification(LNP-MC3),which had a particle size>200 nm,the particle sizes of positively charged LNPs without PEG modification(LNP-Pos),PEG-modified positively charged LNPs(LNP-Pos-P),PEG-modified neutral LNPs(LNP-Neu-P),PEG-modified ionizable LNPs(LNP-MC3-P),and PEG-modified negatively charged LNPs(LNP-Neg-P)were all<200 nm.Zeta potential analysis revealed that the surface charges of the LNPs were the highest in LNP-Pos,followed by LNP-Pos-P,LNP-MC3-P,LNP-Neu-P,LNP-MC3 and LNP-Neg-P.In vivo imaging results indicated that LNP-Pos-P,LNP-Pos and LNP-MC3-P were primarily distributed in the livers,lungs and kidneys,respectively,while LNP-Neu-P and LNP-Neg-P in the livers,kidneys,and lungs,respectively.The distribution of LNP-MC3-P in the brain,heart,spleen and kidneys peaked at 12 h post-injection,but at 24 h in the livers.The distribution of LNP-Pos-P in the lungs peaked at 1 h post-injection.CONCLUSION LNPs are primarily distributed in the livers.Surface charges influence the second most highly-distributed organs.LNP-Pos-P and LNP-MC3-P are the second most highly-distributed in the lungs,and LNP-Neu-P and LNP-Neg-P in the kidneys.

Objective To investigate the level 4 surgical safety management in tertiary public hospitals in Sichuan Province.Methods A combination of questionnaires and qualitative interviews was used to investigate the basic situation of four-level surgery performed,the volume of surgery,and the management of surgery in 34 tertiary public hospitals in Sichuan Province.Results Among the 34 tertiary public hospitals surveyed,the percentage of patients discharged with level Ⅳ surgery in 2023 was 18.96％,which was lower than the level of the percentage of patients discharged with level Ⅳ surgery did not establish a leading group for level Ⅳ surgery (17.65％),a system for preoperative multidisciplinary discussion of level Ⅳ surgery(14.71％),and a system for preoperative multidisciplinary discussion of level Ⅳ surgery with various department-related expert pool(41.18％),multidisciplinary joint examination room(23.53％),and the monitoring and evaluation mechanism for the completion of preoperative multidisciplinary discussion for level 4 surgery(20.59％).Conclusion The volume of level Ⅳ surgeries in tertiary public hospitals in Sichuan Province needs to continue to be improved,and the establishment of a standardized management system for level Ⅳ surgeries is imperative.

Objective To explore the casual relationship between immune cells and chronic pancreatitis(CP)using Mendelian randomization(MR)analysis.Methods The immune cell phenotypes and CP GWAS data used in this study were obtained from public databases,and 731 immune cell phenotypes were included.The bidirectional MR analysis was used to explore the causal relationship between immune cells and CP,and various sensitivity analysis methods were used to verify the heterogeneity and level multiplicity of the results.Results This study identified 33 immune cell phenotypes with a causal relationship with CP,of which 18 were inhibitory factors,and the rest were risk factors.Among the 18 inhibitory factors,CD25 on CD4+in the Treg cell group showed the most significant inhibitory effect.Among the 15 risk factors,CD8br AC in the TBNK cell group,CD8br on TD CD8br in the mature T cell group,and CD39+CD8br％ T cell and CD28 on CD4+in the Treg cell group showed statistical significance.The reverse MR results further confirmed the unidirectionality of the causal relationship.Conclusion Our study revealed the close relationship between immune cells and CP through MR method,highlighting the complex interaction pattern between the immune system and CP.

Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Objective:To explore the clinical phenotypes and hematological characteristics of β-thalassemia combined with α-globin gene triplet.Methods:A retrospective case analysis study was conducted, taking individuals diagnosed with thalassemia who sought for outpatient services in No 1 people′s hospital of Chenzhou affiliated to South China University from August 10, 2021, to December 31, 2023 as study objectives. Among them, there were 8 768 males and 11 707 females, aged 31.5 (23.0, 46.0) years old. Blood analysis were analyzed by hematology analyze.The hemoglobin(Hb) Hb A, HbA 2,Hb F bands were analyzed by Capillary electrophoresis method, and the genotypes of thalassemia were analyzed by high-throughput sequencing technology.Hematological parameters between different genotypes of thalassemia were analyzed using t-tests and calibrated t-tests for data analysis. Results:A total of 27 cases of beta thalassemia combined with alpha globin triplet were detected, The average hemoglobin (Hb) of 11 cases of β Codon41/42 (-CTTT)/β N combined with ααα anti 4.2 (3.7) (92±16)g/L was lower than that of β Codon41/42 (-CTTT)/β N(112±11)g/L, and the difference was statistically significant ( t=3.97, P0.05). The average Hb of 8 cases of β IVS-Ⅱ-654 (CT)/β N combined with ααα anti 4.2 (3.7)(85±21) g/L was lower than that of β IVS-Ⅱ-654 (CT)/β N(116±12) g/L, and the difference was statistically significant ( t=4.05, P0.05). Conclusion:When the mutation site is at Codon41/42 (-CTTT) or IVS-Ⅱ-654 (CT), β-thalassemia combined with alpha globin triplet can make the clinical manifestations of β-thalassemia at this site more pronounced.

Objective To explore the casual relationship between immune cells and chronic pancreatitis(CP)using Mendelian randomization(MR)analysis.Methods The immune cell phenotypes and CP GWAS data used in this study were obtained from public databases,and 731 immune cell phenotypes were included.The bidirectional MR analysis was used to explore the causal relationship between immune cells and CP,and various sensitivity analysis methods were used to verify the heterogeneity and level multiplicity of the results.Results This study identified 33 immune cell phenotypes with a causal relationship with CP,of which 18 were inhibitory factors,and the rest were risk factors.Among the 18 inhibitory factors,CD25 on CD4+in the Treg cell group showed the most significant inhibitory effect.Among the 15 risk factors,CD8br AC in the TBNK cell group,CD8br on TD CD8br in the mature T cell group,and CD39+CD8br％ T cell and CD28 on CD4+in the Treg cell group showed statistical significance.The reverse MR results further confirmed the unidirectionality of the causal relationship.Conclusion Our study revealed the close relationship between immune cells and CP through MR method,highlighting the complex interaction pattern between the immune system and CP.

The prelimbic cortex (PL) plays a critical role in processing both the sensory and affective components of pain. However, the underlying molecular mechanisms remain poorly understood. In this study, we observed a reduction in hyperpolarization-activated cation current (I_h) in layer V pyramidal neurons of the contralateral PL in a mouse model of spared nerve injury (SNI). The expression of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels was also decreased in the contralateral PL. Conversely, microinjection of fisetin, a partial agonist of HCN2, produced both analgesic and anxiolytic effects. Additionally, we found that cyclin-dependent kinase 5 (CDK5) was activated in the contralateral PL, where it formed a complex with HCN2 and phosphorylated its C-terminus. Knockdown of CDK5 restored HCN2 expression and alleviated both pain hypersensitivity and anxiety-like behaviors. Collectively, these results indicate that CDK5-mediated dysfunction of HCN2 in the PL underlies nerve injury-induced mechanical hypersensitivity and anxiety.
Animals ; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels/metabolism* ; Hyperalgesia/metabolism* ; Cyclin-Dependent Kinase 5/metabolism* ; Neuralgia/metabolism* ; Male ; Anxiety/metabolism* ; Mice ; Potassium Channels/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Pyramidal Cells/metabolism*

Objective To investigate the short- and long-term prognoses and the risk factors affecting “textbook outcome” (TO) after laparoscopic pancreaticoduodenectomy (LPD) for pancreatic ductal adenocarcinoma (PDAC). Methods The clinical and follow-up data of patients diagnosed with PDAC and treated with LPD from January 2019 to December 2022 were retrospectively analyzed. The prognosis was compared between TO and non-TO groups, and univariate and multivariate logistic regression analyses were used to identify independent prognostic factors for TO. Results A total of 284 patients were enrolled in this study, including 185 cases in the TO group and 99 cases in the non-TO group. The 1-, 3- and 5-year overall survival (OS) rates of the TO and non-TO groups with PDAC were 87.3% vs. 85.9%, 52.5% vs. 38.4%, and 18.0% vs. 4.5%, respectively (P=0.020); the recurrence-free survival (RFS) rates were 74.1% vs. 65.7%, 27.1% vs. 21.0%, and 10.0% vs. 0%, respectively (P=0.042). Multivariate logistic regression analysis showed that operation time >360 min (OR=0.561, 95%CI: 0.321-0.979, P=0.042), intraoperative blood loss >400 ml (OR=0.392, 95%CI: 0.175-0.879, P=0.023), hard or tough texture of pancreas (OR=2.240, 95%CI: 1.247-4.022, P=0.007), and main pancreatic duct diameter >3 mm (OR=1.931, 95%CI: 1.126-3.312, P=0.017) were independent prognostic factors for TO. Conclusion After the learning curve, more than 60% of patients with PDAC can achieve TO after LPD. The chances of achieving TO are significantly reduced when the operation time >360 min, the intraoperative blood loss >400 ml, the texture of pancreas was soft, and the diameter of the main pancreatic duct >3 mm.