Objective:To analyze the nonlinear correlation and inflection points between age and short-term mortality in patients with negative systemic inflammatory response syndrome (SIRS)sepsis score.Methods:A retrospective cohort study was conducted using the medical information mart for intensive care Ⅳ(MIMIC-Ⅳ)database, which included adult patients with sepsis who were admitted to the intensive care unit(ICU)within 24 hours and did not receive mechanical ventilation or vasoactive drug, with a SIRS score ≤1.Patients were divided into survivors and non-survivors based on 28-day survival.Baseline variables such as age, gender, Charlson Comorbidity Index(CCI), body mass index(BMI), Sequential Organ Failure Assessment(SOFA)score, and initial lactate levels were compared between the two groups.With case fatality rate as the dependent variable, variables with differences in univariate analysis were incorporated into the binary logistic regression model, and baseline variables with statistically significant differences except age were matched according to the 1∶3 propensity score.Restricted cubic spline (RCS) regression was used to analyze the nonlinear relationship between patient age and mortality after matching and to determine the inflection point.Results:A total of 53 150 hospital records in the MIMIC-Ⅳ database were retrospectively screened, and 1 691 adult patients[aged(69.82±14.87)years]diagnosed with sepsis and negative SIRS score within 24 hours of ICU admission were included, with 101(5.97%)deaths within 28 days.Patients in the non-survivor group were older [(73.63±14.55)years vs.(69.58±14.86)years, t=-2.663, P=0.008], had higher CCI(4.38±2.64 vs.2.99±2.34, t=-5.732, P<0.001), and higher SOFA score (8.18±3.58 vs.5.04±2.67, t=-8.664, P<0.001)compared to the survivor group.There were no significant differences in gender, BMI, initial lactate levels, and the suspected infection sites (all P>0.05).Multivariable logistic regression analysis showed that increased age ( OR=1.03, 95% CI: 1.02-1.05, P<0.001), increased CCI ( OR=1.16, 95% CI: 1.06-1.26, P<0.001), and increased SOFA score ( OR=1.34, 95% CI: 1.26-1.43, P<0.001)were significantly associated with increased mortality in patients with negative SIRS score.After including SOFA score and CCI in the propensity score matching, there were 271 survivors and 93 non-survivors.RCS results showed a non-linear association between age and mortality( Poverall=0.001, Pnon-linear=0.001), with a significant increase in the OR for mortality when age exceeded 73 years. Conclusions:In sepsis patients with comparable organ function, the short-term mortality rate of patients with negative SIRS score increases non-linearly with age.These patients have mild symptoms but poor clinical outcomes, necessitating early and enhanced monitoring when age exceeds 73 years.

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.

Objective:To analyze the nonlinear correlation and inflection points between age and short-term mortality in patients with negative systemic inflammatory response syndrome (SIRS)sepsis score.Methods:A retrospective cohort study was conducted using the medical information mart for intensive care Ⅳ(MIMIC-Ⅳ)database, which included adult patients with sepsis who were admitted to the intensive care unit(ICU)within 24 hours and did not receive mechanical ventilation or vasoactive drug, with a SIRS score ≤1.Patients were divided into survivors and non-survivors based on 28-day survival.Baseline variables such as age, gender, Charlson Comorbidity Index(CCI), body mass index(BMI), Sequential Organ Failure Assessment(SOFA)score, and initial lactate levels were compared between the two groups.With case fatality rate as the dependent variable, variables with differences in univariate analysis were incorporated into the binary logistic regression model, and baseline variables with statistically significant differences except age were matched according to the 1∶3 propensity score.Restricted cubic spline (RCS) regression was used to analyze the nonlinear relationship between patient age and mortality after matching and to determine the inflection point.Results:A total of 53 150 hospital records in the MIMIC-Ⅳ database were retrospectively screened, and 1 691 adult patients[aged(69.82±14.87)years]diagnosed with sepsis and negative SIRS score within 24 hours of ICU admission were included, with 101(5.97%)deaths within 28 days.Patients in the non-survivor group were older [(73.63±14.55)years vs.(69.58±14.86)years, t=-2.663, P=0.008], had higher CCI(4.38±2.64 vs.2.99±2.34, t=-5.732, P<0.001), and higher SOFA score (8.18±3.58 vs.5.04±2.67, t=-8.664, P<0.001)compared to the survivor group.There were no significant differences in gender, BMI, initial lactate levels, and the suspected infection sites (all P>0.05).Multivariable logistic regression analysis showed that increased age ( OR=1.03, 95% CI: 1.02-1.05, P<0.001), increased CCI ( OR=1.16, 95% CI: 1.06-1.26, P<0.001), and increased SOFA score ( OR=1.34, 95% CI: 1.26-1.43, P<0.001)were significantly associated with increased mortality in patients with negative SIRS score.After including SOFA score and CCI in the propensity score matching, there were 271 survivors and 93 non-survivors.RCS results showed a non-linear association between age and mortality( Poverall=0.001, Pnon-linear=0.001), with a significant increase in the OR for mortality when age exceeded 73 years. Conclusions:In sepsis patients with comparable organ function, the short-term mortality rate of patients with negative SIRS score increases non-linearly with age.These patients have mild symptoms but poor clinical outcomes, necessitating early and enhanced monitoring when age exceeds 73 years.

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.

Objective To preliminarily understand the current status of medication safety management of medical institutions in China. Methods Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs (INRUD) and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases jointly established a research group. Basing on the voluntary principle,members (medical institutions)of the group did medication safety self-assessment using the questionnaires of "2011 ISMP Medication Safety Self Assessment? for Hospitals (Chinese version)", which included 10 key elements,20 core indicators,and 270 assessment projects. The questionnaires were handed out on August 17,2018 and needed to be completed and submitted within 2 months. Results As of October 19,2018,67 hospitals of 16 provincial administrative regions in total had submitted their questionnaires,including 61 (91. 0％)3A hospitals and 6 (9％)2A hospitals. The average value of total scores of medication safety self-assessment in the 67 hospitals was 58. 9％ (7. 6％ -90. 0％). None of the 67 hospitals evaluated the key element Ⅵ(medication device acquisition,use,and monitoring). The scores of the other 9 key elements from high to low were 67. 6％,66. 2％,65. 1％,64. 8％,64. 1％,58. 2％, 54. 5％,54. 4％,and 52. 5％ respectively for element Ⅶ (environmental factors,workflow and staffing patterns),element Ⅳ(drug labeling,packaging and nomenclature),element Ⅸ (patient education), element Ⅲ(communication of drug orders and other drug information),element Ⅷ (staff competency and education),element Ⅴ(drug standardization,storage and distribution),element Ⅹ (quality processes and risk management),element Ⅰ (patient information),and element Ⅱ (drug information). Conclusion The data of medication safety from 67 hospitals of 16 provincial administrative regions were obtained through the first national self-assessment questionnaire survey in medical institutions,which initially reflected the current status of medication safety in medical institutions in China.

Objective To preliminarily understand the current status of medication safety management of medical institutions in China. Methods Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs (INRUD) and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases jointly established a research group. Basing on the voluntary principle,members (medical institutions)of the group did medication safety self-assessment using the questionnaires of "2011 ISMP Medication Safety Self Assessment? for Hospitals (Chinese version)", which included 10 key elements,20 core indicators,and 270 assessment projects. The questionnaires were handed out on August 17,2018 and needed to be completed and submitted within 2 months. Results As of October 19,2018,67 hospitals of 16 provincial administrative regions in total had submitted their questionnaires,including 61 (91. 0％)3A hospitals and 6 (9％)2A hospitals. The average value of total scores of medication safety self-assessment in the 67 hospitals was 58. 9％ (7. 6％ -90. 0％). None of the 67 hospitals evaluated the key element Ⅵ(medication device acquisition,use,and monitoring). The scores of the other 9 key elements from high to low were 67. 6％,66. 2％,65. 1％,64. 8％,64. 1％,58. 2％, 54. 5％,54. 4％,and 52. 5％ respectively for element Ⅶ (environmental factors,workflow and staffing patterns),element Ⅳ(drug labeling,packaging and nomenclature),element Ⅸ (patient education), element Ⅲ(communication of drug orders and other drug information),element Ⅷ (staff competency and education),element Ⅴ(drug standardization,storage and distribution),element Ⅹ (quality processes and risk management),element Ⅰ (patient information),and element Ⅱ (drug information). Conclusion The data of medication safety from 67 hospitals of 16 provincial administrative regions were obtained through the first national self-assessment questionnaire survey in medical institutions,which initially reflected the current status of medication safety in medical institutions in China.