Objective To identify core targets of hepatocellular carcinoma (HCC) by using bioinformatics and specific algorithms, explore their relationships with immune cells, and investigate the causal relationships between immune cells and HCC through Mendelian randomization. Methods Relevant genes associated with the development of HCC were screened using the GEO and TCGA databases. Immune infiltration analysis was conducted using GSVA and CIBERSORT algorithms. A bidirectional Mendelian randomization analysis was then performed to explore the causal relationships between immune cells and HCC. Results A total of 284 HCC-related genes were identified, with 120 genes recognized within the protein interaction network. Immune infiltration analysis revealed significant correlations between key genes and immune cells. Mendelian randomization results indicated that HLA DR on CD33⁺ HLA DR⁺ CD14dim (OR=1.097, 95%CI: 1.002–1.201, P=0.045, P_Bonferroni=0.091) and CD8 on CD28⁺ CD45RA⁺ CD8⁺ T cell (OR=1.123, 95%CI: 1.027–1.228, P=0.011, P_Bonferroni=0.022) were the risk factors for HCC. Conversely, HLA DR⁺⁺ monocyte absolute count was identified as a protective factor for HCC (OR=0.812, 95%CI: 0.702–0.938, P=0.005, P_Bonferroni=0.139). Conclusion The occurrence and development of liver cancer may be related to CDK1, CCNB1, and CDC20, showing a high degree of correlation with Th2 cells, T helper cells, Th17 cells, and DCs. Mendelian randomization shows that HLA DR on CD33⁺HLA DR⁺ CD14dim and CD8 on CD28⁺CD45RA⁺CD8⁺T cells are associated with an increased risk of HCC. The risk of hepatocellular carcinoma is associated with a decrease in the level of HLA DR⁺⁺monocyte absolute count.

Objective:To explore how one-sided/two-sided brain blood flow affects the occurrence of neurological complications in patients with Stanford type A aortic dissection, as well as to assess the factors that contribute to the development of neurological complications.Methods:A total of 162 patients diagnosed with Stanford type A aortic dissection who had undergone ascending aorta and total aortic arch replacement at Affiliated Hospital of Jining Medical College from August 2020 to December 2023 were retrospectively reviewed. These patients were categorized into two groups based on the presence of postoperative neurological complications: a group with neurological complications comprising 77 cases and a group without neurological complications comprising 85 cases. A comparative analysis was carried out on general clinical data, surgical and brain perfusion characteristics, as well as preoperative test indicators between these two groups in order to investigate the factors influencing the occurrence of postoperative neurological complications in patients with Stanford type A aortic dissection. The data was analyzed using Logistic regression to identify the risk factors associated with postoperative neurological complications and to develop a predictive nomogram model. Calibration curves, receiver operating characteristic (ROC) curves and decision curve (DCA) were generated to assess the accuracy and predictive capability of the nomogram model.Results:In the group of patients who experienced neurological complications, there was a higher prevalence of a history of hypertension, longer operation time, extended periods of cardiopulmonary bypass, cross-clamping, brain perfusion, cooling, and rewarming, as well as increased postoperative drainage volume. Additionally, the levels of preoperative blood urea nitrogen (BUN), creatinine (Cr) and lactic acid (Lac) were elevated compared to those in the non-neurological complications group: 77.9% (60/77) vs. 52.9% (45/85), (409.99 ± 104.26) min vs. (348.29 ± 63.12) min, (223.36 ± 66.86) min vs. (179.25 ± 38.59) min, 112 (94, 133) min vs. 96 (84, 113) min, (35.23 ± 9.89) min vs. (32.14 ± 6.81) min, (82.19 ± 28.69) min vs. (68.76 ± 29.06) min, (79.30 ± 22.60) min vs. (69.54 ± 16.42) min, 806 (529, 1 127) ml vs. 663 (449, 925) ml, 6.78 (5.38, 8.84) mmol/L vs. 6.08 (4.66, 7.76) mmol/L, 86.3 (64.0, 131.9) μmol/L vs. 71.0 (55.6, 84.9) μmol/L, 2.1(1.2, 4.0) mmol/L vs. 1.5 (0.9, 2.3) mmol/L. On the other hand, the percentage of patients who underwent bilateral brain perfusion was lower, and they experienced lower lowest temperature, preoperative platelet count, and ejection fraction levels than those in the non-neurological complications group: 57.1% (44/77) vs. 75.3% (64/85), (25.69 ± 1.04) ℃ vs. (26.04 ± 0.82) ℃, (175.79 ± 58.14) ×10 9/L vs. (213.87 ± 77.29) ×10 9/L, (54.18 ± 3.84)% vs. (55.34 ± 3.56)% ( P<0.05). Multivariate Logistic regression analysis revealed that a prior history of high blood pressure, prolonged cardiopulmonary bypass duration were identified as autonomous risk factors for the development of postoperative neurological issues in individuals with Stanford type A aortic dissection, while simultaneous brain perfusion emerged as an independent protective element ( P<0.05). Subsequently, a predictive nomogram was constructed incorporating these three pivotal factors to assess the likelihood of postoperative neurological complications in patients with Stanford type A aortic dissection. The calibration curve exhibited a noteworthy level of accuracy for the nomogram predictive model ( χ2 = 9.01, P = 0.342). Additionally, the ROC curve analysis displayed an area under the curve of 0.84 (95% CI 0.78 to 0.90) for the nomogram model in predicting postoperative neurological complications in patients with Stanford type A aortic dissection, indicating a high predictive accuracy. Moreover, DCA analysis indicated that the nomogram model provided a net benefit above 0 across the spectrum of 0 to 90%. Conclusions:Postoperative neurological complications in patients with Stanford type A aortic dissection is linked to factors such as a previous history of hypertension, unilateral brain perfusion, an extended cardiopulmonary bypass duration. By developing a nomogram model that incorporates these factors, it becomes feasible to accurately forecast the likelihood of postoperative neurological complications in this patient population. This predictive tool holds significant value in facilitating proactive clinical risk evaluation and preventive measures.

Objective To investigate the predictive value of β3-adrenergic receptor(β3-AR)expression levels for recurrence after radiofrequency ablation in patients with atrial fibrillation(AF).Methods Patients with AF who underwent their first radiofrequency ablation in the Department of Cardiology from January 2022 to February 2024(AF group,n=166)and healthy individuals undergoing routine medical check-ups during the same period(control group,n=100)were selected as study subjects.Based on whether AF recurred after the procedure during follow-up,AF patients were divided into a non-recurrence group and a recurrence group.General clinical data and relevant laboratory indices of AF patients were collected.The relative expression lev-el of lymphocyte β3-AR mRNA was measured using fluorescence real-time quantitative PCR.Multivariate lo-gistic regression analysis was used to identify risk factors for AF recurrence after surgery,and receiver operat-ing characteristic(ROC)curve analysis was employed to evaluate the predictive value of β3-AR mRNA ex-pression levels for AF recurrence after ablation.Results After 9 months of follow-up post-radiofrequency ab-lation,among 166 AF patients,42 experienced recurrence,with a recurrence rate of 25.3%.Compared with the non-recurrence group,patients in the recurrence group had significantly higher levels of sST2,IL-6 and left at-rial diameter(LAD),with a statistically significant differences(P<0.05).The relative expression level of β3-AR was higher in the recurrence group than in the non-recurrence group,with a statistically significant differ-ence(P<0.05).Multivariate logistic regression analysis showed that LAD,sST2,IL-6,and β3-AR were inde-pendent risk factors for AF recurrence after surgery(P<0.05).ROC curve analysis indicated that the area under the curve for β3-AR mRNA relative expression level in predicting AF recurrence after radiofrequency ablation was 0.884(95%CI:0.794 to 0.975;P<0.05).Conclusion High preoperative expression levels of β3-AR in AF patients are associated with recurrence after radiofrequency ablation,and β3-AR can serve as a potential biological marker for predicting AF recurrence.

Objective To explore the application value of combining the ultrasound breast imaging reporting and data system(BI-RADS)classification with serum fibroblast growth factor receptor 1(FGFR1)and growth differentiation factor 3(GDF3)in the differential diagnosis of benign and malignant breast masses.Methods A total of 159 patients with breast masses were selected and divided into the benign mass group(n=83)and the malignant mass group(n=76)based on postoperative pathological diagnosis.All patients underwent ultrasound examination,and enzyme-linked immunosorbent assay(ELISA)was applied to detect serum levels of FGFR1 and GDF3.Receiver operating characteristic(ROC)curve was applied to analyze the diagnostic value of ultrasound BI-RADS classification and serum FGFR1 and GDF3 levels for benign and malignant breast masses.Kappa test was applied to analyze the consistency between various diagnostic methods and pathological diagnosis.Results The serum levels of FGFR1 and GDF3,the proportions of irregular morphology,unclear boundaries,spiculation,microcalcifications,blood flow grade Ⅱ-Ⅲ and posterior echo attenuation,RI and PI were higher in the malignant tumor group than those in the benign tumor group(P＜0.05).The area under the curve(AUC)of FGFR1,GDF3 and ultrasound BI-RADS classification in the differential diagnosis of benign and malignant breast masses separately and in combination was 0.802(95%CI:0.732-0.871),0.817(95%CI:0.751-0.884),0.848(95%CI:0.784-0.912)and 0.956(95%CI:0.918-0.993),respectively.The combined diagnosis was more effective than that of the individual diagnosis of each indicator.The consistency between the individual and combined diagnosis of benign and malignant breast masses and pathological diagnosis showed that the Kappa values were 0.517,0.514,0.688 and 0.912,respectively,with the highest consistency observed in the combined diagnosis(P＜0.05).Conclusion Ultrasound BI-RADS classification combined with serum FGFR1 and GDF3 has high application value in the differential diagnosis of benign and malignant breast masses.

Objective:To review the application of internet cognitive behavioral therapy (CBT) in perinatal women with negative emotions, point out the limitations of existing studies, and put forward development suggestions for future research.Methods:Using the Scope review guide published by Joanna Briggs Institute as the methodological framework, eight Chinese and English databases including China National Knowledge Infrastructure (CNKI), Wanfang, PubMed and Web of Science were searched until July 1, 2024, and the literatures were collected and analyzed.Results:A total of 18 literatures were included. The interventionists of internet cognitive behavioral therapy were mostly psychologists; the intervention methods were mostly in the form of partial participation of therapists, and the intervention platforms were mostly websites. The intervention content was centered on mental health education, emotional monitoring, cognitive reconstruction, behavioral activation training, and problem solving. There were 15 studies that demonstrated that internet cognitive behavioral therapy was effective, and three studies showed that internet cognitive behavioral therapy was not effective in improving negative emotions in perinatal women, but perinatal women responded to treatment.Conclusions:The Internet cognitive behavioral therapy can effectively improve the negative emotions of perinatal pregnant women, but the long-term effect is not clear. Future studies can expand the sample size and follow up the effect for a long time.

Objective Through in vitro experiments,biomechanical data of the transtibial pullout suture(TPS),tendon reconstruction(TR),and tendon reconstruction with suture augmentation(TRS)were collected,so as to evaluate the biomechanical effectiveness of tendon reconstruction for repairing medial meniscus posterior root tear(MMPRT).Methods Eighteen porcine knee joint models were divided into TPS,TR,and TRS groups.Sutures were used to fix the meniscal root in TPS group.Tendons were passed through an incision at the meniscal root in TR group.Tendons were passed through an incision at the meniscal root and secured at tendon-meniscus contact area with additional sutures in TRS group.The sutures and tendons were pulled out through tibial tunnels and fixed at the anteromedial tibia.All groups underwent failure load tests,and ultimate failure load,displacement at failure load,load at clinical failure,stiffness,and failure modes of the samples were recorded.Results The maximum failure load in TPS group was significantly higher than that in TR group(P＜0.05),but there was no significant difference between TPS group and TRS group(P＞0.05).The maximum failure load in TRS group was significantly higher than that in TR group(P＜0.05).The displacement under failure load in TR group and TRS group was significantly lower than that in TPS group(P＜0.05),but there was no significant difference between TR group and TRS group(P＞0.05).There were no significant differences in the load under clinical failure among the 3 groups(P＞0.05).The stiffness of TRS group was significantly greater than that of TPS group(P＜0.05),but no significant difference was observed between TR group and TPS group,as well as between TR group and TRS group(P＞0.05).All failures were caused by suture or tendon cutting through the meniscus.Conclusions The tendon reconstruction techniques is superior to the TPS in terms of failure displacement and stiffness,while the TRS further enhances the stability of the repair.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.

Objective:To explore how one-sided/two-sided brain blood flow affects the occurrence of neurological complications in patients with Stanford type A aortic dissection, as well as to assess the factors that contribute to the development of neurological complications.Methods:A total of 162 patients diagnosed with Stanford type A aortic dissection who had undergone ascending aorta and total aortic arch replacement at Affiliated Hospital of Jining Medical College from August 2020 to December 2023 were retrospectively reviewed. These patients were categorized into two groups based on the presence of postoperative neurological complications: a group with neurological complications comprising 77 cases and a group without neurological complications comprising 85 cases. A comparative analysis was carried out on general clinical data, surgical and brain perfusion characteristics, as well as preoperative test indicators between these two groups in order to investigate the factors influencing the occurrence of postoperative neurological complications in patients with Stanford type A aortic dissection. The data was analyzed using Logistic regression to identify the risk factors associated with postoperative neurological complications and to develop a predictive nomogram model. Calibration curves, receiver operating characteristic (ROC) curves and decision curve (DCA) were generated to assess the accuracy and predictive capability of the nomogram model.Results:In the group of patients who experienced neurological complications, there was a higher prevalence of a history of hypertension, longer operation time, extended periods of cardiopulmonary bypass, cross-clamping, brain perfusion, cooling, and rewarming, as well as increased postoperative drainage volume. Additionally, the levels of preoperative blood urea nitrogen (BUN), creatinine (Cr) and lactic acid (Lac) were elevated compared to those in the non-neurological complications group: 77.9% (60/77) vs. 52.9% (45/85), (409.99 ± 104.26) min vs. (348.29 ± 63.12) min, (223.36 ± 66.86) min vs. (179.25 ± 38.59) min, 112 (94, 133) min vs. 96 (84, 113) min, (35.23 ± 9.89) min vs. (32.14 ± 6.81) min, (82.19 ± 28.69) min vs. (68.76 ± 29.06) min, (79.30 ± 22.60) min vs. (69.54 ± 16.42) min, 806 (529, 1 127) ml vs. 663 (449, 925) ml, 6.78 (5.38, 8.84) mmol/L vs. 6.08 (4.66, 7.76) mmol/L, 86.3 (64.0, 131.9) μmol/L vs. 71.0 (55.6, 84.9) μmol/L, 2.1(1.2, 4.0) mmol/L vs. 1.5 (0.9, 2.3) mmol/L. On the other hand, the percentage of patients who underwent bilateral brain perfusion was lower, and they experienced lower lowest temperature, preoperative platelet count, and ejection fraction levels than those in the non-neurological complications group: 57.1% (44/77) vs. 75.3% (64/85), (25.69 ± 1.04) ℃ vs. (26.04 ± 0.82) ℃, (175.79 ± 58.14) ×10 9/L vs. (213.87 ± 77.29) ×10 9/L, (54.18 ± 3.84)% vs. (55.34 ± 3.56)% ( P<0.05). Multivariate Logistic regression analysis revealed that a prior history of high blood pressure, prolonged cardiopulmonary bypass duration were identified as autonomous risk factors for the development of postoperative neurological issues in individuals with Stanford type A aortic dissection, while simultaneous brain perfusion emerged as an independent protective element ( P<0.05). Subsequently, a predictive nomogram was constructed incorporating these three pivotal factors to assess the likelihood of postoperative neurological complications in patients with Stanford type A aortic dissection. The calibration curve exhibited a noteworthy level of accuracy for the nomogram predictive model ( χ2 = 9.01, P = 0.342). Additionally, the ROC curve analysis displayed an area under the curve of 0.84 (95% CI 0.78 to 0.90) for the nomogram model in predicting postoperative neurological complications in patients with Stanford type A aortic dissection, indicating a high predictive accuracy. Moreover, DCA analysis indicated that the nomogram model provided a net benefit above 0 across the spectrum of 0 to 90%. Conclusions:Postoperative neurological complications in patients with Stanford type A aortic dissection is linked to factors such as a previous history of hypertension, unilateral brain perfusion, an extended cardiopulmonary bypass duration. By developing a nomogram model that incorporates these factors, it becomes feasible to accurately forecast the likelihood of postoperative neurological complications in this patient population. This predictive tool holds significant value in facilitating proactive clinical risk evaluation and preventive measures.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*