Objective:To investigate the clinical demand for subcutaneous immunotherapy (SCIT) with pet allergens and explore the sensitization characteristics of patients undergoing pet SCIT.Methods:A cross-sectional retrospective analysis was conducted on patients diagnosed with pet allergies and treated with pet allergen SCIT in our outpatient clinic from January 2019 to December 2023. Patients were categorized into three groups based on the type of SCIT received: single-cat SCIT group, single-dog SCIT group, and combined cat-dog SCIT group.Results:A total of 931 patients were included, the age range was 5-65 years (median age of 30 years), with 283 male and 648 female. Among them, 67.7%( n=630) received single-cat SCIT, 10.9% ( n=102)received single-dog SCIT, and 21.4% ( n=199) received combined cat-dog SCIT. The number of patients receiving pet allergen SCIT increased annually. Patients in the single-dog SCIT group were significantly older than those in the other two groups ( H=41.329, P<0.001) and had a lower prevalence of allergic rhinitis (91.2% vs. 96.5% and 98.5%; χ2=10.400, P=0.006). In the combined cat-dog SCIT group, the allergy rate to mold allergens was significantly higher than in the single-cat SCIT group (12.6% vs. 4.9%, χ2=13.965, P=0.001). In the single-dog SCIT group, the allergy rate to spring pollen allergens was significantly higher than in the other two groups ( χ2=15.731, P<0.001), and the allergy rate to autumn pollen allergens was significantly higher than in the single-cat SCIT group ( χ2=13.459, P=0.001). There was no significant difference in the dust mite allergy rate among the three groups( χ2=4.117, P=0.129). In the single-dog SCIT group, patients with asthma were significantly older than those without asthma (41.2 vs. 35.2 years old, t=-2.073, P=0.041). In both the single-cat and single-dog SCIT groups, the proportion of allergic rhinitis in the asthma group(91.2%,78.3%) was significantly lower than that in the non-asthma group(97.4%,94.9%) ( χ2=8.863,6.158; P=0.008,0.026). In the single-cat SCIT group, non-asthmatic patients were significantly more likely to receive SCIT combined with spring pollen allergens compared to asthmatic patients (23.9% vs. 11.0%, χ2=7.586, P=0.006). Conclusions:The demand for pet allergen SCIT has steadily increased over the years, with a predominance of female patients. Sensitization profiles varied among patients receiving SCIT for different pet allergens. This study comprehensively elucidates the clinical demand and sensitization characteristics of patients undergoing pet allergen SCIT, providing valuable reference data for clinical diagnosis and treatment.

Objective:To identify the risk factors for ascending aortic dilatation and develop a prediction model using LASSO-Logistic regression in patients with normally functioning bicuspid aortic valves（BAV）.Methods:Eight-four adult patients with BAV diagnosed as having normal valve function by transthoracic echocardiography who attended to the General Hospital of Ningxia Medical University between June 2024 and April 2025 were prospectively selected，there were 42 patients with ascending aortic dilatation and 42 patients without dilatation.The patients were divided into a training set（60 cases）and a test set（24 cases）using stratified random sampling at a ratio of 7 to 3 via the R caret package. All subjects underwent transthoracic echocardiography，lipid and plasma matrix metalloproteinases（MMP）and tissue inhibitors（TIMP）levels detection. The inverse probability of treatment weighting（IPTW）method was employed to control for potential confounding factors. LASSO and multifactorial binary Logistic regression was applied to screen the independent risk factors for ascending aortic dilatation of BAV and development a nomogram prediction model. The accuracy，consistency and clinical applicability of the prediction model were evaluated by applying the ROC curve，calibration curve，and decision curve analysis（DCA），respectively.Results:①After adjustment for IPTW，LASSO-Logistic regression analysis identified left ventricular global longitudinal strain（LVGLS）and plasma MMP-2 levels as independent risk factors for ascending aortic dilatation in BAV patients with normal valve function.②The nomogram prediction model constructed based on the above screening features，and the area under the curve（AUC）of ROC for the training set and test set were 0.917 and 0.903，with specificities of 0.867 and 0.917，and sensitivities of 0.933 and 0.916，respectively. ③Calibration curves demonstrated satisfactory alignment，with C-indices of 0.908（95% CI=0.879～0.937）for the training set and 0.903（95% CI=0.874 - 0.932）for the test set. Hosmer-Lemeshow goodness-of-fit tests indicated strong consistency between predicted and observed outcomes，with P-values of 0.138 and 0.750 for the training and test sets，respectively.The DCA curve demonstrated that within a threshold probability range of 0.04 - 0.90 in the test set，the clinical decision-making model provided a higher net benefit rate for patients with BAV. Conclusions:LVGLS absolute value reduction and elevated plasma MMP-2 levels are independent risk factors for predicting ascending aortic dilatation in BAV patients with normal valve function. The prediction model based on LASSO-Logistic regression has good predictive value，providing a scientific basis for clinical decision-making in patients with BAV and aortic diseases.

Objective:To analyze the changes in the costs of hospital rehabilitation after the reform of health insurance payments in the past 6 years, and to identify relevant factors which can provide a reference for the reform of the health insurance payment system in rehabilitation department.Methods:Information on 16, 827 patients hospitalized in the rehabilitation department of The First Affiliated Hospital of Xi′an Jiaotong University between May 2018 and May 2024 was collected and subjected to non-parametric analysis.Results:The average hospitalization cost of rehabilitation department patients over the six years was Y14, 574.92±10, 524.79. During that time the proportion of the cost attributable to Western medicine decreased from 17.1% in 2018 to 7.6% in 2024. The proportion of the patients with hypertension was 51.94%, followed by diabetes mellitus (20.10%). Those with infections had the highest total hospitalization costs. Motor disorders were the most common dysfunction (59.02%), followed by speech disorders (17.45%). Patients with swallowing disorders had the highest hospitalization costs. After the payment system shifted from fee-for-service (FFS) to payment by diagnosis-related group (DRG) in 2023, the average daily inpatient expenditures for rehabilitation patients with all types of diseases gradually declined, reaching its lowest level in 2024.Conclusions:After the health insurance payments shifted from FFS to DRG, the proportion of in patients′ total drug costs decreased annually, and the average daily costs of patients with different types of diseases also decreased significantly, but the comprehensive service fee and diagnostic costs increased.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

BACKGROUND:It has been proved that induced pluripotent stem cells can differentiate into cardiomyocytes,but there are few reports on the maturity of differentiated cardiomyocytes.OBJECTIVE:To explore the effect of prolonging the induced differentiation time on the morphology,sarcomere length,binuclear cell content,cardiac gene expression,cardiac protein expression,and mitochondrial function of cardiomyocytes derived from induced pluripotent stem cells.METHODS:Bone morphogenetic protein 4,CH IR 99021,and IWR1 were used to induce pluripotent stem cells to differentiate into cardiomyocytes,and differentiated cardiomyocytes were collected on days 20 and 40 respectively.The expression levels of cardiac genes and proteins in differentiated cardiomyocytes were detected by RT-PCR and immunofluorescence,respectively.LAS X image analysis software was used to analyze the morphology and sarcomere length of differentiated cardiomyocytes.MitoTracker Green FM mitochondrial staining was used to detect total mitochondria.JC-1 mitochondrial staining was used to detect mitochondrial membrane potential.RESULTS AND CONCLUSION:Differentiated card io myocytes on day 40 had longer cell circumference and sarcomere length,and larger cell area than those on day 20(P＜0.05).The proportion of multinucleated cells rose sharply from about 16％on day 20 to about 29％on day 40(P＜0.05).Differentiated cardiomyocytes on day 40 had gene expression levels that were more similar to those of the primary cardiomyocytes,and the expression levels of SERCA2A,Cx-43,and α-MHC genes were significantly higher than on day 20(P＜0.05).Compared with the differentiated cardiomyocytes on day 20,the expression density of TNNT2 and α-MHC protein was relatively higher,the distribution density of mitochondria was larger,and the number of functional mitochondria was greater on day 40(P＜0.05).The results show that prolonging the induced differentiation time can increase the maturity of differentiated cardiomyocytes by increasing the length of sarcomere and the number of functional mitochondria,as well as improving the expression levels of cardiac genes and proteins.

Objective:To investigate the clinical demand for subcutaneous immunotherapy (SCIT) with pet allergens and explore the sensitization characteristics of patients undergoing pet SCIT.Methods:A cross-sectional retrospective analysis was conducted on patients diagnosed with pet allergies and treated with pet allergen SCIT in our outpatient clinic from January 2019 to December 2023. Patients were categorized into three groups based on the type of SCIT received: single-cat SCIT group, single-dog SCIT group, and combined cat-dog SCIT group.Results:A total of 931 patients were included, the age range was 5-65 years (median age of 30 years), with 283 male and 648 female. Among them, 67.7%( n=630) received single-cat SCIT, 10.9% ( n=102)received single-dog SCIT, and 21.4% ( n=199) received combined cat-dog SCIT. The number of patients receiving pet allergen SCIT increased annually. Patients in the single-dog SCIT group were significantly older than those in the other two groups ( H=41.329, P<0.001) and had a lower prevalence of allergic rhinitis (91.2% vs. 96.5% and 98.5%; χ2=10.400, P=0.006). In the combined cat-dog SCIT group, the allergy rate to mold allergens was significantly higher than in the single-cat SCIT group (12.6% vs. 4.9%, χ2=13.965, P=0.001). In the single-dog SCIT group, the allergy rate to spring pollen allergens was significantly higher than in the other two groups ( χ2=15.731, P<0.001), and the allergy rate to autumn pollen allergens was significantly higher than in the single-cat SCIT group ( χ2=13.459, P=0.001). There was no significant difference in the dust mite allergy rate among the three groups( χ2=4.117, P=0.129). In the single-dog SCIT group, patients with asthma were significantly older than those without asthma (41.2 vs. 35.2 years old, t=-2.073, P=0.041). In both the single-cat and single-dog SCIT groups, the proportion of allergic rhinitis in the asthma group(91.2%,78.3%) was significantly lower than that in the non-asthma group(97.4%,94.9%) ( χ2=8.863,6.158; P=0.008,0.026). In the single-cat SCIT group, non-asthmatic patients were significantly more likely to receive SCIT combined with spring pollen allergens compared to asthmatic patients (23.9% vs. 11.0%, χ2=7.586, P=0.006). Conclusions:The demand for pet allergen SCIT has steadily increased over the years, with a predominance of female patients. Sensitization profiles varied among patients receiving SCIT for different pet allergens. This study comprehensively elucidates the clinical demand and sensitization characteristics of patients undergoing pet allergen SCIT, providing valuable reference data for clinical diagnosis and treatment.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

BACKGROUND:It has been proved that induced pluripotent stem cells can differentiate into cardiomyocytes,but there are few reports on the maturity of differentiated cardiomyocytes.OBJECTIVE:To explore the effect of prolonging the induced differentiation time on the morphology,sarcomere length,binuclear cell content,cardiac gene expression,cardiac protein expression,and mitochondrial function of cardiomyocytes derived from induced pluripotent stem cells.METHODS:Bone morphogenetic protein 4,CH IR 99021,and IWR1 were used to induce pluripotent stem cells to differentiate into cardiomyocytes,and differentiated cardiomyocytes were collected on days 20 and 40 respectively.The expression levels of cardiac genes and proteins in differentiated cardiomyocytes were detected by RT-PCR and immunofluorescence,respectively.LAS X image analysis software was used to analyze the morphology and sarcomere length of differentiated cardiomyocytes.MitoTracker Green FM mitochondrial staining was used to detect total mitochondria.JC-1 mitochondrial staining was used to detect mitochondrial membrane potential.RESULTS AND CONCLUSION:Differentiated card io myocytes on day 40 had longer cell circumference and sarcomere length,and larger cell area than those on day 20(P＜0.05).The proportion of multinucleated cells rose sharply from about 16％on day 20 to about 29％on day 40(P＜0.05).Differentiated cardiomyocytes on day 40 had gene expression levels that were more similar to those of the primary cardiomyocytes,and the expression levels of SERCA2A,Cx-43,and α-MHC genes were significantly higher than on day 20(P＜0.05).Compared with the differentiated cardiomyocytes on day 20,the expression density of TNNT2 and α-MHC protein was relatively higher,the distribution density of mitochondria was larger,and the number of functional mitochondria was greater on day 40(P＜0.05).The results show that prolonging the induced differentiation time can increase the maturity of differentiated cardiomyocytes by increasing the length of sarcomere and the number of functional mitochondria,as well as improving the expression levels of cardiac genes and proteins.

Objective Under the operation background of Diagnosis-Intervention Packet(DIP),whether there is interaction between reducing medical cost and average length of stay combined with pre-hospitalization mode,and whether there is difference between different departments and diseases in interaction.Methods Based on real-world data from 71 453 patients admitted to Guizhou Provincial People's Hospital from July to December 2021,a two-way analysis of variance was employed.When the interaction effect was statistically significant,parameter estimation was used to determine the magnitude and direction of the interaction effect,followed by subgroup analyses by department and disease.Results Without adjustment,both total medical costs and average length of stay exhibited a negative interaction effect(P＜0.05).Subgroup analyses revealed that in terms of total medical costs,the effect size for the surgical system was 0.18％,lower than that for the internal medicine system(0.70％);for core diseases,it was 6.62％,lower than that for comprehensive diseases(7.71％).Regarding average length of stay,the effect size for the surgical system was 0.55％,better than that for the internal medicine system(0.22％);for core diseases,it was 8.70％,higher than that for comprehensive diseases(2.90％).Conclusion The combination of DIP payment reform and pre-admission management model demonstrates a synergistic effect,effectively reducing patients' medical costs and length of stay.This effect is influenced by disease complexity and the standardization of diagnostic and treatment processes.

Objective:To analyze the changes in the costs of hospital rehabilitation after the reform of health insurance payments in the past 6 years, and to identify relevant factors which can provide a reference for the reform of the health insurance payment system in rehabilitation department.Methods:Information on 16, 827 patients hospitalized in the rehabilitation department of The First Affiliated Hospital of Xi′an Jiaotong University between May 2018 and May 2024 was collected and subjected to non-parametric analysis.Results:The average hospitalization cost of rehabilitation department patients over the six years was Y14, 574.92±10, 524.79. During that time the proportion of the cost attributable to Western medicine decreased from 17.1% in 2018 to 7.6% in 2024. The proportion of the patients with hypertension was 51.94%, followed by diabetes mellitus (20.10%). Those with infections had the highest total hospitalization costs. Motor disorders were the most common dysfunction (59.02%), followed by speech disorders (17.45%). Patients with swallowing disorders had the highest hospitalization costs. After the payment system shifted from fee-for-service (FFS) to payment by diagnosis-related group (DRG) in 2023, the average daily inpatient expenditures for rehabilitation patients with all types of diseases gradually declined, reaching its lowest level in 2024.Conclusions:After the health insurance payments shifted from FFS to DRG, the proportion of in patients′ total drug costs decreased annually, and the average daily costs of patients with different types of diseases also decreased significantly, but the comprehensive service fee and diagnostic costs increased.