Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Its occurrence secondary to hepatobiliary malignancies is even rarer, and without timely diagnosis and treatment, the mortality rate is extremely high. There is a need to raise awareness of this disease. This report describes a case of a 70-year-old female patient diagnosed with AHA 2 months after surgery for cholangiocarcinoma, admitted to the Second Affiliated Hospital of Bengbu Medical College in October 2022. The patient presented with subcutaneous hematoma in both lower limbs. Coagulation function tests showed a markedly prolonged activated partial thromboplastin time (APTT) of 74.5 seconds, with no correction in the APTT mixing test. Coagulation factor assays revealed a severely reduced coagulation factor VIII activity (FVIII:C) of 0.3%, and an inhibitor titer of 25.6 BU/mL was detected. After ruling out other potential causes, the patient was diagnosed with cholangiocarcinoma-associated AHA. With chemotherapy to control the primary tumor, alongside hemostatic and immunosuppressive therapy for inhibitor eradication, AHA was brought under control. The patient had no further coagulation abnormalities or bleeding, enabling timely and full-course chemotherapy for cholangiocarcinoma and significantly improving survival and quality of life. Therefore, in patients with malignancies who present with spontaneous bleeding or unusual bleeding following surgery, trauma, or invasive procedures, clinicians should be alert to the possibility of secondary AHA. Timely diagnosis and treatment can significantly improve prognosis.
Humans ; Cholangiocarcinoma/surgery* ; Female ; Hemophilia A/drug therapy* ; Aged ; Bile Duct Neoplasms/surgery* ; Factor VIII

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

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective To investigate the mechanism of metformin for regulating tumor-stromal cell cross-talk in breast cancer.Methods Tumor associated fibroblasts(CAFs)co-cultured with breast cancer cells were treated with metformin,and the changes in expressions of hypoxia-inducible factor-1α(HIF-1α),p-AMPK,stroma-derived factor-1(SDF-1)and interleukin-8(IL-8)in the CAFs were detected using ELISA,RT-qPCR or Western blotting;Transwell assay was used to evaluate the invasiveness of the tumor cells and its changes following treatment with exogenous SDF-1,IL-8 and TGF-β1.The effects of HIF-1α shRNA or overexpression plasmid,AMPK shRNA,and treatment with OG(a proline hydroxylase inhibitor)or 2-OXO(a proline hydroxylase activator)were examined on p-AMPK,HIF-1α,SDF-1 and IL-8 expressions and invasiveness of the CAFs.Results Metformin treatment significantly increased the expression levels of p-AMPK,SDF-1 and IL-8(P<0.05)and decreased HIF-1α expression(P<0.05)without affecting AMPK expression level(P>0.05)in the CAFs.The invasion ability of metformin-treated breast cancer cells was significantly decreased(P<0.05).Exogenous SDF-1 and IL-8,HIF-1α overexpression,and OG-induced upregulation of HIF-1α all significantly attenuated the inhibitory effects of metformin on breast cancer cell invasion(P<0.05)and HIF-1α,SDF-1 and IL-8 expressions in CAFs(P<0.05).Transfection with HIF-1α shRNA or treatment with 2-OXO significantly decreased the invasiveness of breast cancer cells(P<0.05).P-AMPK knockdown significantly suppressed the inhibitory effect of metformin on HIF-1α expression in CAFs and on invasion of breast cancer cells(P<0.05).Treatment with TGF-β1 partially decreased the inhibitory effect of metformin on HIF-1α expression in CAFs and invasiveness of the breast cancer cells(P<0.05).Conclusion Metformin suppresses HIF-1α expression in CAFs to block tumor-stromal cross talk in breast cancer.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.

Objective:Optimizing and upgrading the accounting methods and approaches for each dimension by comparing and analyzing the practical effects of the full-dimension costing path in public hospitals.Methods:List the mainstream accounting paths guided by the current cost accounting plan for public hospitals,to compare the advantages and disadvantages of the results of each type of accounting methods and their degree of difficulty,and to optimize and upgrade the details of accounting in all dimensions.Re-sults:Different accounting methods have their own advantages and disadvantages,and the path selection needs to rely on the scale of public hospitals,management needs,accounting level and information construction degree and other comprehensive factors,that is,with the selection of accounting paths in each dimension from simple to fine,the degree of data refinement and reference strength are correspondingly from weak to strong.Conclusion:Public hospitals should combine their own accounting basic conditions,choose the best accounting methods and paths,build a cost accounting control system,and continuously optimize and upgrade the ac-counting model,in order to provide strong decision-making support for hospitals to find out the asset base,strengthen resource allo-cation and improve data governance capabilities.