Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P＜0.05 or P＜0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P＜0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P＜0.05 or P＜0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P＜0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.

OBJECTIVE To develop a long-acting light-protective nanogel with both physical barrier and chemical clearance functions， and evaluate its performance. METHODS The photoprotective nanogel composed of mussel mucin and sodium hyaluronate was constructed based on a fullerenol-cerium oxide composite nano system， namely fullerenol-cerium oxide nanogel （FCN）， and was characterized. The antioxidant capacity of FCN was evaluated using in vitro free radical scavenging experiments； its UV shielding ability was assessed by using an SPF value detector； its biosafety was assessed according to the requirements of the Guidelines for Drug Safety Evaluation； skin adhesion was assessed using small animal 3D live imaging technology； its sun protection ability was assessed through skin sunscreen detection and histopathological observation. RESULTS The average particle sizes of cerium oxide and fullerenol nanoparticles in FCN were about 20 and 10 nm， respectively， and FCN exhibited good UV absorption and free radical scavenging abilities. SPF value of FCN was 58.95±0.82， and the ultraviolet A protection level value was 6.21±0.15. No pathogenic colonies such as Staphylococcus aureus， were detected in the nanogel， and the contents of lead， arsenic， mercury and cadmium all met the standards for pharmaceutical excipients； FCN group did not show any irritating reactions such as erythema， edema， or desquamation； blood biochemical indicators of the FCN group were within the normal reference range. The material clearance rate of mice in the artificial sweat flushing group was less than 30%， while the material clearance rate of mice in the dry cleaning group reached about 92%. The mice in the protective group did not show obvious erythema or ulcer formation throughout the experiment. Histopathology showed that the fibers were arranged in an orderly manner， and the number of collagen fibers was close to that of the control group. CONCLUSIONS The FCN formulation constructed in this study meets the relevant requirements of the Chinese Pharmacopoeia， has good safety and skin compatibility， and achieves dual synergistic protection of UV shielding and free radical scavenging.

Objective:To explore the application effects of the solution-focused approach combined with empathic nursing in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) .Methods:A total of 96 AMI patients who underwent PCI in the Department of Cardiology at Cangzhou Central Hospital from March 2020 to March 2023 were selected using convenience sampling. They were randomly assigned to an experimental group ( n=48) and a control group ( n=48) using a random number table. The control group received routine nursing care, while the experimental group received a solution-focused approach combined with empathic nursing. Medication adherence, coping strategies, and patient satisfaction were compared between the two groups. Results:After the intervention, medication adherence and satisfaction scores in the experimental group were significantly higher than those in the control group, and the differences werestatistically significant ( P<0.05) . Additionally, the experimental group scored higher in confrontation coping, and lower in avoidance and resignation coping than the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The combination of a solution-focused approach and empathic nursing can effectively improve medication adherence, coping strategies, and patient satisfaction in AMI patients after PCI.

Objective:To explore the effect and mechanism of USP7 on immune and inflammatory response of EV71 infection.Methods:THP-1 cells were induced to differentiate into t-Mφ cells by PMA,cells were treated by targeted USP7 inhibitor P22077,and divided into DMSO control group and P22077 experimental group,and infected with EV71.ELISA was used to detect supernatant concentration of IL-6,CCL3,TNF-α of cells separately.RT-qPCR was used to detect RNA expression of EV71-VP1,plaque test was used to detect virus titer in cell supernatant.Western blot was used to detect expressions and phosphorylation of molecules related to innate immune signaling pathway.Full-length plasmid Myc-USP7 and Flag-MDA5 were constructed and transfected into HEK293T cells,and Co-IP was used to detect external interaction between USP7 and MDA5 with Myc antibody and Flag antibody,respectively.Infected t-Mφ cells with EV71,and Co-IP detection of their interaction by USP7 and MDA5 antibodies,respectively.t-Mφ cells of DMSO control group and P22077 experimental group were infected with EV71,CHX test was used to detect expression of MDA5 and downstream related molecules.Transfected Flag-MDA5,Myc-USP7,HA-Ub or HA-K48 plasmids,Co-IP detection of ubiquitination and ubiquitination types of MDA5 regulated by USP7 with Flag antibody.Co-IP detection of MDA5 ubiquitination types regulated by USP7 in t-Mφ cells by using MDA5 antibodies.Results:After infected with EV71 and inhibited of USP7,mRNA and protein expres-sions of IL-6,CCL3 and TNF-α were decreased(P<0.05),while EV71 replication(P<0.05),and titer increased;expression of MDA5,and activation of p-IKKα/β,p-IκBα and p-p65 in innate immunity signal pathway decreased.Interaction between USP7 and MDA5 could inhibit MDA5 degradation by inhibiting K48 ubiquitination of MDA5.Conclusion:USP7 stabilizes MDA5 expression by inhibiting K48 ubiquitination of MDA5,thereby positively regulating EV71 infection immunity and inflammatory response.

Objective:To explore the effect and mechanism of USP7 on immune and inflammatory response of EV71 infection.Methods:THP-1 cells were induced to differentiate into t-Mφ cells by PMA,cells were treated by targeted USP7 inhibitor P22077,and divided into DMSO control group and P22077 experimental group,and infected with EV71.ELISA was used to detect supernatant concentration of IL-6,CCL3,TNF-α of cells separately.RT-qPCR was used to detect RNA expression of EV71-VP1,plaque test was used to detect virus titer in cell supernatant.Western blot was used to detect expressions and phosphorylation of molecules related to innate immune signaling pathway.Full-length plasmid Myc-USP7 and Flag-MDA5 were constructed and transfected into HEK293T cells,and Co-IP was used to detect external interaction between USP7 and MDA5 with Myc antibody and Flag antibody,respectively.Infected t-Mφ cells with EV71,and Co-IP detection of their interaction by USP7 and MDA5 antibodies,respectively.t-Mφ cells of DMSO control group and P22077 experimental group were infected with EV71,CHX test was used to detect expression of MDA5 and downstream related molecules.Transfected Flag-MDA5,Myc-USP7,HA-Ub or HA-K48 plasmids,Co-IP detection of ubiquitination and ubiquitination types of MDA5 regulated by USP7 with Flag antibody.Co-IP detection of MDA5 ubiquitination types regulated by USP7 in t-Mφ cells by using MDA5 antibodies.Results:After infected with EV71 and inhibited of USP7,mRNA and protein expres-sions of IL-6,CCL3 and TNF-α were decreased(P<0.05),while EV71 replication(P<0.05),and titer increased;expression of MDA5,and activation of p-IKKα/β,p-IκBα and p-p65 in innate immunity signal pathway decreased.Interaction between USP7 and MDA5 could inhibit MDA5 degradation by inhibiting K48 ubiquitination of MDA5.Conclusion:USP7 stabilizes MDA5 expression by inhibiting K48 ubiquitination of MDA5,thereby positively regulating EV71 infection immunity and inflammatory response.

Objective:To explore the application effects of the solution-focused approach combined with empathic nursing in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) .Methods:A total of 96 AMI patients who underwent PCI in the Department of Cardiology at Cangzhou Central Hospital from March 2020 to March 2023 were selected using convenience sampling. They were randomly assigned to an experimental group ( n=48) and a control group ( n=48) using a random number table. The control group received routine nursing care, while the experimental group received a solution-focused approach combined with empathic nursing. Medication adherence, coping strategies, and patient satisfaction were compared between the two groups. Results:After the intervention, medication adherence and satisfaction scores in the experimental group were significantly higher than those in the control group, and the differences werestatistically significant ( P<0.05) . Additionally, the experimental group scored higher in confrontation coping, and lower in avoidance and resignation coping than the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The combination of a solution-focused approach and empathic nursing can effectively improve medication adherence, coping strategies, and patient satisfaction in AMI patients after PCI.

Objective To investigate the protective effect of Liraglutide in rats with diabetic kidney disease(DKD)by regulating the nuclear factor E2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4)ferroptosis signaling pathway.Methods Twelve male Sprague-Dawley(SD)rats were randomly divided into normal control(NC)group,DKD group,and Liraglutide treatment(Lir)group,with 4 rats in each group.The 24 hUAlb,TC,TG,LDL-C,serum creatinine(Scr),BUN,ferrous ion(Fe2+),the activity of glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)were detected in each group.Hematoxylin and eosin(HE),periodic acid-Schiff(PAS),and periodic acid-silver methenamine-Masson(PASM-Masson)staining were used to observe the pathological changes of the kidneys.Immunofluorescence was performed to detect the localization and expression of reactive oxygen species(ROS)in the renal tissue.The protein expressions of Nrf2 and GPX4 were detected by Western blot.Results Compared with the NC group,the levels of 24 hUAlb,Scr,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were increased(P＜0.05 or P＜0.01),while the expressions of GSH-Px,Nrf2,and GPX4 proteins were decreased in the DKD group(P＜0.01).Compared with the DKD group,the levels of 24 hUAlb,BUN,TC,TG,LDL-C,MDA,ROS,and Fe2+were decreased(P＜0.05 or P＜0.01),and the expressions of GSH-Px,Nrf2,and GPX4 proteins were increased in the Lir group(P＜0.01).Conclusions Liraglutide may exert a protective effect in DKD by upregulating the Nrf2/GPX4 signaling pathway and inhibiting ferroptosis.

Objective To explore the role and potential mechanisms of all-trans retinoic acid(ATRA)on activation and oxidative stress of hepatic stellate cell(HSC).Methods Platelet-derived growth factor(PDGF-bb,10 ng/ml)was applied to induce the activation of HSCs,which was then treated with ATRA at a dosage of 5 μmol/L for 48 h.The effects of ATRA on HSC activation were evaluated by detecting changes in cell growth viability and phenotypic marker expression.The effects of ATRA on HSC oxidative stress were evaluated by detecting changes in intracellular reactive oxygen species(ROS),reduced glutathione(GSH)and malondialdehyde(MDA),and the expression of antioxidant genes.The effects of ATRA on HSC autophagic activity were evaluated by detecting changes in autophagy marker expression and autophagic flow.Results Compared with the PDGF-bb group,the cell viability was significantly reduced in ATRA-treated HSCs(P＜0.01),as well as the expression of α-SMA and Collagen I.The intracellular levels of ROS and MDA were significantly reduced in ATRA-treated HSCs(P＜0.01),whereas the GSH level was significantly increased(P＜0.01).The expression levels of antioxidant genes(NRF2,HO-1,and ATF4),were significantly higher in ATRA-treated HSCs than those in the normal ones under PDGF-bb condition(P＜0.01).Meanwhile,the expression of autophagy markers Beclin 1 and LC3 Ⅱ/I,and signal of autophagy flow in ATRA-treated HSCs were found to be significantly reduced(P＜0.01).Conclusion ATRA significantly inhibited PDGF-bb-induced HSC activation and reduced the level of oxidative stress and autophagic activity of HSCs,which had potential applications in the prevention and treatment of liver fibrosis.

Objective:To investigate the application effect of high-altitude field-based teaching in acute mountain sickness.Methods:The medical students of the classes 2018 and 2019 majoring in clinical medicine were selected as subjects, and they were divided into conventional teaching group and field-based teaching group, with 20 students in each group. The students in the conventional teaching group received classroom teaching alone, and those in the field-based teaching group received high-altitude field-based teaching after theoretical lectures. The two groups were compared in terms of the theoretical knowledge of acute mountain sickness, the quality score of internship, and rescue operation score of acute mountain sickness, and questionnaire feedback and post-class discussion were performed among trainees and teachers to evaluate the high-altitude field-based teaching model. SPSS 19.0 was used for statistical analysis.Results:Compared with the conventional teaching group, the field-based teaching group had significantly higher scores of the theoretical knowledge of acute mountain sickness (91.72±4.34 vs. 86.10±5.15, P<0.001), the quality score of internship (89.64±5.21 vs. 83.51±2.38, P<0.001), and the rescue operation of acute mountain sickness [94.05 (89.54, 94.87) vs. 87.01 (84.33, 90.82), P<0.001]. Conclusions:High-altitude field-based teaching can improve the teaching effect of acute mountain sickness and cultivate the interest and learning enthusiasm of students, and therefore, it holds promise for wide application.

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved ¹O₂ generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.