Objective In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.

Objective In view of the potential threat of adverse drug reaction(ADR)to patients'health and the limitations of traditional monitoring methods,this study investigates the construction method of an ADR knowledge graph based on a knowledge-driven technology path to promote the intelligent upgrading of pharmacovigilance field.Methods In this study,an adverse drug reaction knowledge base was established,and the data within the knowledge base were preprocessed.The BERT-CRF model was utilized to identify and extract the relevant entities,relationships and attribute information,and knowledge alignment was carried out by combining the rule method and statistical method.The knowledge fusion data was stored in the Neo4j graph database to construct the knowledge graph.Results Based on the established knowledge base,this study explored the method of constructing knowledge graph of adverse drug reaction by knowledge-driven technology,laying the groundwork for data mining and the development of intelligent auxiliary system tools based on knowledge graph.Conclusions The study on the construction method of an ADR knowledge graph based on a knowledge-driven technology path provides a new perspective and technical path for the intelligent upgrading of pharmacovigilance field.It holds important theoretical and practical significance for improving drug safety,protecting patients'health,and promoting the healthy development of pharmaceutical industry.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

Objective:To evaluate the role of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO-1) signaling pathway in the attenuation of endotoxin-induced acute lung injury (ALI) by hydromorphone and the relationship with Golgi apparatus stress (GA stress) in mice.Methods:Eighteen SPF wild-type (WT) and 18 Nrf2 knockout (Nrf2 KO) male C57BL/6J mice, aged 6-8 weeks, weighing 18-20 g, were divided into 3 groups ( n=6 each) using a random number table method: control groups (WT+ Con group, Nrf2 KO+ Con group), ALI groups (WT+ ALI group, Nrf2 KO+ ALI group) and ALI+ hydromorphone groups (WT+ ALI+ HM group, Nrf2 KO+ ALI+ HM group). ALI was induced by injecting lipopolysaccharide (LPS) 15 mg/kg via the tail vein in anesthetized animals. Hydromorphone 120 μg was intraperitoneally injected at 15 min before LPS injection in WT+ ALI+ HM group and Nrf2 KO+ ALI+ HM group, and the equal volume of normal saline was given instead in control groups. The animals were sacrificed after anesthesia at 12 h after LPS injection, and lung tissues were obtained for examination of the pathological changes which were scored and Golgi ultrastructure (with a transmission electron microscope) and for determination of the content of malondialdehyde (MDA), activity of superoxide dismutase (SOD), and expression of Nrf2, HO-1 and Golgi stress-related markers (Golgi matrix protein 130 [GM130], Golgi autoantigen 97 kDa [Golgin-97], ATPase secretory pathway Ca 2+ Transporting 1 [ATP2C1], Golgi phosphoprotein 3 [GOLPH3]) (by Western blot). Results:Compared with WT+ Con group and Nrf2 KO+ Con group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), no significant changes were found in the expression of Nrf2 and HO-1 ( P>0.05), and the damage to the Golgi apparatus was aggravated in WT+ ALI group and Nrf2 KO+ ALI group. Compared with WT+ ALI group, the lung injury scores and content of MDA were significantly decreased, the activity of SOD was increased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was up-regulated, the expression of GOLPH3 was down-regulated ( P<0.05), and the damage to the Golgi apparatus was significantly attenuated in WT+ ALI+ HM group. Compared with Nrf2 KO+ ALI group, the lung injury scores were significantly decreased, and the activity of SOD was increased ( P<0.05), no significant changes were found in the content of MDA and expression of Nrf2, HO-1, GM130, Golgin-97, ATP2C1 and GOLPH3 ( P>0.05), and no significant reduction in the damage to the Golgi apparatus was found in Nrf2 KO+ ALI+ HM group. Compared with WT+ ALI+ HM group, the lung injury scores and content of MDA were significantly increased, the activity of SOD was decreased, the expression of Nrf2, HO-1, GM130, Golgin-97 and ATP2C1 was down-regulated, the expression of GOLPH3 was up-regulated ( P<0.05), and the damage to the Golgi apparatus was aggravated in Nrf2 KO+ ALI+ HM group. Conclusions:Nrf2/HO-1 signaling pathway is involved in the attenuation of endotoxin-induced ALI by hydromorphone, and it is associated with the inhibition of Golgi stress.

The objective of this study is to assess the current status of vaccination against respiratory disease among the elderly aged ≥60 and analyze the factors influencing vaccination rates at both service provider and recipient levels in Zhejiang Province. Using a stratified random sampling method, a questionnaire survey was conducted from September 2022 to January 2023 among elderly people aged ≥60 in 30 townships/streets in Zhejiang Province, as well as immunization planning staff at the provincial, municipal, county/district, and township/street levels. Logistic regression models were used to analyze the factors related to vaccination among elderly people in Zhejiang Province. Based on the Zhejiang Provincial Comprehensive Management Information System for Vaccine and Vaccination, the systematic coverage rates of influenza vaccine and pneumonia vaccine for the elderly were 21.76% and 4.57%, respectively. Multivariate logistic regression analysis indicated that advanced age ( OR=1.74, 95% CI: 1.51-1.99), knowing that influenza is more severe than the common cold ( OR=1.67, 95% CI: 1.37-2.04) and having heard of the influenza vaccine ( OR=9.78, 95% CI: 7.03-13.59) were motivating factors for elderly to receive influenza vaccines. Advanced age ( OR=1.71, 95% CI: 1.43-2.06), knowing the serious consequences of pneumonia in the elderly ( OR=1.93, 95% CI: 1.47-2.55) and knowing that pneumonia vaccines can prevent pneumonia ( OR=6.36, 95% CI: 4.84-8.36) were motivating factors for elderly to receive pneumonia vaccines. Zhejiang Immunization Program staff believed that the main reasons why the elderly aged ≥60 would not be vaccinated against influenza or pneumonia were that they felt they would not get sick (55.52% and 56.35% respectively), it would not be serious if get sick (47.73% and 37.46% respectively), lacking trust in vaccine efficacy and safety (38.31% and 43.69% respectively). Vaccination rates for influenza and pneumonia vaccines among the elderly aged ≥60 in Zhejiang Province are suboptimal. Advanced age, awareness of the severity of respiratory diseases and awareness of vaccines against such diseases are related factors for elderly individuals to receive influenza and pneumonia vaccines.

The objective of this study is to assess the current status of vaccination against respiratory disease among the elderly aged ≥60 and analyze the factors influencing vaccination rates at both service provider and recipient levels in Zhejiang Province. Using a stratified random sampling method, a questionnaire survey was conducted from September 2022 to January 2023 among elderly people aged ≥60 in 30 townships/streets in Zhejiang Province, as well as immunization planning staff at the provincial, municipal, county/district, and township/street levels. Logistic regression models were used to analyze the factors related to vaccination among elderly people in Zhejiang Province. Based on the Zhejiang Provincial Comprehensive Management Information System for Vaccine and Vaccination, the systematic coverage rates of influenza vaccine and pneumonia vaccine for the elderly were 21.76% and 4.57%, respectively. Multivariate logistic regression analysis indicated that advanced age ( OR=1.74, 95% CI: 1.51-1.99), knowing that influenza is more severe than the common cold ( OR=1.67, 95% CI: 1.37-2.04) and having heard of the influenza vaccine ( OR=9.78, 95% CI: 7.03-13.59) were motivating factors for elderly to receive influenza vaccines. Advanced age ( OR=1.71, 95% CI: 1.43-2.06), knowing the serious consequences of pneumonia in the elderly ( OR=1.93, 95% CI: 1.47-2.55) and knowing that pneumonia vaccines can prevent pneumonia ( OR=6.36, 95% CI: 4.84-8.36) were motivating factors for elderly to receive pneumonia vaccines. Zhejiang Immunization Program staff believed that the main reasons why the elderly aged ≥60 would not be vaccinated against influenza or pneumonia were that they felt they would not get sick (55.52% and 56.35% respectively), it would not be serious if get sick (47.73% and 37.46% respectively), lacking trust in vaccine efficacy and safety (38.31% and 43.69% respectively). Vaccination rates for influenza and pneumonia vaccines among the elderly aged ≥60 in Zhejiang Province are suboptimal. Advanced age, awareness of the severity of respiratory diseases and awareness of vaccines against such diseases are related factors for elderly individuals to receive influenza and pneumonia vaccines.

Objective To observe the effect and mechanism of extracts of Liangxue Tongyu Recipe(LTR) on acute cerebral hemorrhage rats. Methods Twelve SD rats were randomly divided into sham operation group, model group, LTR water-extract group and LTR alcohol-extract group. Rats of sham operation group were injected with 2μL of normal saline into the left caudate nucleus, and rats of the other groups were injected with 2μL (0.25 U/ μL) of type Ⅶ collagenase into the left caudate nucleus to induce the model of acute cerebral hemorrhage. And then the rats of LTR groups were given intra-gastric gavage of LTR water-extract or LTR alcohol-extract. At the end of the experiment, we observed the macroscopic features of rat brain, pathological changes in rat brain under microscope after HE staining, awake time, rectal temperature, neurobehavioral scores and serum-specific enolase (NSE) level. Results Rats except for the sham operation group had various degrees of right hemiplegia symptoms, and the symptoms became severest on the third day of experiment. LTR alcohol-extract group and water-extract group had an effect on improving neurobehavioral scores, shortening awake time, and decreasing rectal temperature and serum NSE level of model rats. Conclusion LTR alcohol-extract and water-extract can relieve acute cerebral hemorrhage induced by type Ⅶcollagenase .

Aim To evaluate the protective effects of salvianolic acid B on the ISO-induced myocardial is-chemic injury model of rats and the influence of regula-ting NLRP3 associated protein on myocardial ischemia. Method All rats were randomly divided into control group, model group and Sal B 5, 10, 15 mg · kg-1 groups. For 7 days, rats in Sal B groups were given by introperitoneal injection of 5, 10, 15 mg·kg-1 Sal B, rats in control group and model group were given the same volume of normal saline. Rats were subcutane-ously multi-point injected ISO ( 30 mg · kg-1 ) for 2 days on the fifth administrating day. The myocardial protective effect of Sal B was evaluated from electrocar-diogram( ECG), myocardial tissue pathological chan-ges, serum myocardial enzymes, oxidation index and inflammatory cytokine, myocardial tissue of NLRP3 related protein expression. Results Sal B could re-duce the degree of myocardial tissue necrosis and the infiltration of inflammatory cells, reduce T-wave values of ECG(P<0. 05 or P<0. 01). Compared with model group, CK values, GOT values and IL-1β values of rats in different dose groups were significantly lower, and MDA values and LDH values of rats in middle-and high-dose groups were significantly lower ( P<0. 05 or P<0. 01 ) . However, T-SOD values of rats middle-and high-dose groups were significantly higher ( P <0. 05 or P<0. 01). Meanwhile,the NLRP3, Caspase-1 and IL-1β protein level in myocardial tissue of the rats in different dose groups compared with model group had reduced ( P <0. 05 or P <0. 01 ) . Conclu-sion Sal B has protective effects on myocardial ische-mic rats, its mechanism may be related with inhibition of decreasing the expression of NLRP3 inflammasome associated protein, which can suppress the generation of inflammatory cytokines.