Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Objective:To explore the influence of injection methods of different contrast agents on CMR image quality,and further optimize"one-stop"examination process under the premise of the analysis for high-pressure bolus pressure curve of contrast-enhanced(CE)cardiac magnetic resonance(CMR).Methods:The data of CMR examination of 70 patients with old myocardial infarction who admitted to the department of emergency of Xuanwu Hospital,Capital Medical University from December 2023 to December 2024 were selected as research objects.They were divided into an observation group and a control group by a simple randomization method,with 35 cases in each group.The observation group adopted gadolinium contrast agent injection with double-phase double-flow,with two bolus injections at 4 ml/s and 2 ml/s sequentially.The control group adopted the injection with single-phase double-flow,with only one bolus injection at 4 ml/s.The dynamic pressure time curve was drawn,and the total bolus dose and pressure peak of two kinds of injection methods were compared.The residual liquid samples of the observation group and the control group were collected after injection of contrast agent was conducted.After the residual liquids of 10 ml,20 ml and 30 ml were derived respectively,the T1 mapping sequence was used to collect signal intensity values,and to compared the difference of that between two groups.The signal-to-noise ratio(SNR)of left ventricular blood pool,infarcted myocardium and distal myocardium,and the contrast-to-noise ratios(CNR)between infarcted myocardium and blood pool,and between distal myocardium and blood pool were compared between the observation group and the control group.Results:There was no statistical difference in the total dose of bolus injection between the observation group and the control group(P>0.05).The peak value of the pressure of bolus injection in the observation group and control group were respectively(87.4±11.3)pound force per square inch(PSI)and(104.0±20.1)PSI,and the difference was statistically significant(t=5.81,P<0.05).T1 signal intensity values of 10 ml residual liquid and 20 mL residual liquid were respectively 1984.43±70.26 and 2190.56±195.96 in observation group,and they were respectively 1203.36±184.99 and 2884.64±349.39 in control group,and the differences were significant(t=-3.57,6.03,P<0.05).The T1 signal intensity value of 30mL residual fluid sample was 4371.75±75.16 in observation group,and that was 4261.86±110.68 in control group,and the difference was no significant(P>0.05).The SNR value of blood pool was(4.88±1.01)in observation group,which was lower than(8.25±1.36)in control group,and the difference of that between two groups was significant(t=6.11,P<0.05).The CNR values of infarcted myocardium and blood pool,of remote myocardium and blood pool between two groups were statistically significant(t=-4.79,-5.39,P<0.05).Conclusion:The contrast agent of high-pressure bolus injection with dual-phase dual-flow method can not only explore the time window of the extravasation of contrast agent,but also improve the SNR and the CNR of CMR images,and further optimize the CMR examination process.

Objective:To explore the influence of injection methods of different contrast agents on CMR image quality,and further optimize"one-stop"examination process under the premise of the analysis for high-pressure bolus pressure curve of contrast-enhanced(CE)cardiac magnetic resonance(CMR).Methods:The data of CMR examination of 70 patients with old myocardial infarction who admitted to the department of emergency of Xuanwu Hospital,Capital Medical University from December 2023 to December 2024 were selected as research objects.They were divided into an observation group and a control group by a simple randomization method,with 35 cases in each group.The observation group adopted gadolinium contrast agent injection with double-phase double-flow,with two bolus injections at 4 ml/s and 2 ml/s sequentially.The control group adopted the injection with single-phase double-flow,with only one bolus injection at 4 ml/s.The dynamic pressure time curve was drawn,and the total bolus dose and pressure peak of two kinds of injection methods were compared.The residual liquid samples of the observation group and the control group were collected after injection of contrast agent was conducted.After the residual liquids of 10 ml,20 ml and 30 ml were derived respectively,the T1 mapping sequence was used to collect signal intensity values,and to compared the difference of that between two groups.The signal-to-noise ratio(SNR)of left ventricular blood pool,infarcted myocardium and distal myocardium,and the contrast-to-noise ratios(CNR)between infarcted myocardium and blood pool,and between distal myocardium and blood pool were compared between the observation group and the control group.Results:There was no statistical difference in the total dose of bolus injection between the observation group and the control group(P>0.05).The peak value of the pressure of bolus injection in the observation group and control group were respectively(87.4±11.3)pound force per square inch(PSI)and(104.0±20.1)PSI,and the difference was statistically significant(t=5.81,P<0.05).T1 signal intensity values of 10 ml residual liquid and 20 mL residual liquid were respectively 1984.43±70.26 and 2190.56±195.96 in observation group,and they were respectively 1203.36±184.99 and 2884.64±349.39 in control group,and the differences were significant(t=-3.57,6.03,P<0.05).The T1 signal intensity value of 30mL residual fluid sample was 4371.75±75.16 in observation group,and that was 4261.86±110.68 in control group,and the difference was no significant(P>0.05).The SNR value of blood pool was(4.88±1.01)in observation group,which was lower than(8.25±1.36)in control group,and the difference of that between two groups was significant(t=6.11,P<0.05).The CNR values of infarcted myocardium and blood pool,of remote myocardium and blood pool between two groups were statistically significant(t=-4.79,-5.39,P<0.05).Conclusion:The contrast agent of high-pressure bolus injection with dual-phase dual-flow method can not only explore the time window of the extravasation of contrast agent,but also improve the SNR and the CNR of CMR images,and further optimize the CMR examination process.

OBJECTIVES: To explore the damage effects of chronic restraint stress (CRS) on amygdala cells through the rat CRS model. METHODS: The rat CRS model was established, and the changes in body weight and adrenal mass in control group and CRS group were monitored at 1 d, 7 d, 14 d and 21 d. The behavior changes were evaluated by the percentage of retention time of open arms and open arm entries using the elevated plus maze (EPM). ELISA was used to detect the concentrations of rat's corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol. The changes of expression of glucocorticoid receptor (GR) and glial fibrillary acidic protein (GFAP) in amygdala were determined by immunohistochemistry and Western blotting. Ultrastructure changes of glial cell were observed by transmission electron microscopy. The apoptosis rate of amygdala was measured by flow cytometry. RESULTS: Compared with the control group at the same time points, body weight of CRS 1 d, 7 d, 14 d and 21 d groups increased slowly, but adrenal mass increased significantly; the serum level of CRH, cortisol and ACTH increased significantly at 7 d, 14 d and 21 d respectively; the expression of GR in amygdala was increased while that of GFAP was decreased; EPM test suggested that the percentage of retention time of open arms and open arm entries decreased significantly after 14 d. The CRS group showed different degrees of glial cell damage in amygdala, and the apoptosis rate of glial cell was significantly increased in 21 d group. CONCLUSIONS This study successfully established a CRS model in rats, and anxiety-like behavioral changes in model rats may be caused by apoptosis of amygdala astrocytes.
Rats ; Animals ; Hydrocortisone/pharmacology* ; Amygdala/metabolism* ; Adrenocorticotropic Hormone/pharmacology* ; Apoptosis ; Body Weight

Objective To set up a mouse model of spondyloarthritis,analyzethe clinical phenotype,radiographic and pathological features,and investigate the therapeutic effect of cysteine-rich 61 (CCN1) monoclonal antibody in spondyloarthritis mouse model.Methods Proteoglycan from bovine nasal septum was used for immunization of 14-16 week old female BALB/c mice.CCN1 monoclonal antibody 093G9 or control immunoglobulin (Ig)G were injected to the spondyloarthritis mice.The arthritis scores were analyzed by t test.Peripheral and axial joints disease development was assessed by Micro-CT and histology.Results Proteoglycan immunized mice began to develop peripheral arthritis in the 8th week.The peripheral arthritis score reached the peak (10.5±1.5) in the 11th week,with the inflammation and spur formation of the ankle and knee joint.We found infiltration of inflammation cells in intervertebral discs of the lumbar vertebrae and the caudal vertebrae.Chondrocyte proliferation couldbe seen in the meniscus of knee and lumbar intervertebral discs.In the 18th week,the intervertebral discsof thoracic vertebrae and the cervical vertebrae were also damaged.Abundant chondrocytesgathered in the intervertebra] discs.The inflammation and new bone for-marion of peripheral and axial joints were more severe in control IgG group than 093G9 group.The peripheral arthritis score in the 093G9 group decreased significantly after 2 treatments,[(2.8±1.3) vs (4.2±2.1),t=2.516,P＜0.05].The difference in arthritis scores between the two groups was the most significant after 8.treatments,[(2.0±2.0)vs (5.3±2.0),t=4.082,P＜0.01].Conclusion The mouse model of spondyloarthritissimulates human spondyloarthritis,including inflammation and new bone formation in p()gheral and axial joints.CCN1 monoclonal antibody can improve the inflammation and new bone formation inspondyloarthritis mouse model.

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.

;Objective To investigate the influence of pharmacist inter-vention on patients′knowledge of anticoagulation therapy with warfarin . Methods Two hundred sixteen patients who were admitted to cardiovas-cular wards and were prescribed anticoagulation therapy with warfarin from October 2013 to August 2014 were included in the study .According to the ward they stayed , patients were divided into control group ( Cardiology ward No1.) and intervention group ( Cardiology ward No 2.) . In the control group , physicians and nurses introduced anticoagulation knowledge for the patients as usual , while intervention group received medication education and guidance on warfarin use by pharmacists .All patients of two groups filled out an assessment questionnaire about warfa-rin anticoagulation at discharge ( outpoint =13 ) .If any answer to the questions was wrong , pharmacists would educate them again .The score of the questionnaire were compared between the two groups . Results The intervention group enrolled 112 patients while the control group enrolled 104 patients. Scores of assessment questionnaire at discharge of the intervention group and the control group were (10.50 ±2.24) vs (8.08 ±2.61) respectively,with statistical difference ( P <0.05 ) .Conclusion Knowledge of warfarin therapy was much better in patients who received pharmacist intervention than patients who received usual care . Integrated management model with pharmacist interventions can improve patients′cognition in anticoagulation therapy with warfarin .