Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Purpose/Significance To introduce the knowledge graph technology in the field of electronic information into the study of traditional Chinese medicine(TCM)terminology,and to demonstrate the dialectical relationship between the therapeutic effects of TCM and its nature,flavor,meridians and TCM diseases in a vivid way.Method/Process The top-down ontology construction method is adopted to build the top-level structure of TCM ontology on the Protégé platform.Taking the 2020 edition of the Chinese Pharmacopoeia as the data source,the TCM information in the pharmacopoeia is split and extracted,and the information of each axis is sorted,disambiguated and nor-malized.With the help of the Protégé platform,entities and relationships are created,and the TCM triple data is output in RDF data for-mat.Finally,the Neo4j graph database is used to store and display the RDF data to form a systematic TCM knowledge graph.Result/Con-clusion It mainly realizes the construction of the knowledge graph of TCM in the pharmacopoeia,and fully reveals the complex knowledge system structure in the field of TCM through data statistical analysis,knowledge measurement and drawing of visual graphics.

ObjectiveTo investigate the composition and changing trend of the etiologies of liver failure in Shaanxi Province, China. MethodsA retrospective analysis was performed for the clinical data of 975 patients with liver failure who were hospitalized in The First Affiliated Hospital of Xi’an Jiaotong University from January 2008 to December 2017. According to the clinical type of liver failure, the patients were divided into acute liver failure (ALF) group with 115 patients, subacute liver failure (SALF) group with 165 patients, and acute-on-chronic liver failure (ACLF) group with 695 patients. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the t-test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. ResultsDrug was the primary cause of ALF (25.22%, 29/115), followed by hepatitis B virus (HBV) infection (21.74%, 25/115); HBV infection was the primary cause of SALF (35.15%, 58/165), followed by drug (27.27%, 45/165); HBV infection was the primary cause of ACLF (87.19%, 606/695), followed by alcohol (3.45%, 24/695). The main age distribution of patients with liver failure due to HBV infection, alcohol, and drug was 20-60 years (595/689), 30-40 years (22/32), and 30-70 years (67/89), respectively. There was a significant reduction in the proportion of patients with HBV-related liver failure in the recent 5 years (61.52% vs 81.33%, χ2=45.87, P＜0.001), while there were significant increases in the proportion of patients with drug-induced liver failure (13.14% vs 4.44%, χ2=22.10, P＜0.001) and alcoholic liver failure (4.76% vs 1.56%, χ2=7.85, P=0005). Further analysis showed that the age of onset of HBV-related liver failure in the recent 5 years was significantly higher than that in the first 5 years (45.3±13.0 vs 42.5±12.9, t=-2.567, P=0.011). ConclusionManagement of chronic HBV infection is still an important link in the control of liver failure, and meanwhile, the prevention and treatment of drug-induced and alcoholic liver diseases should be strengthened. More attention should be paid to the treatment of elderly patients with liver failure.