Objective:To investigate the effects of ginkgolide B on neurological function recovery and the Wnt/β-catenin pathway after ischemic stroke in mice.Methods:Fifty-five C57/BL6 mice were selected, of which 10 mice were kept as the sham group and the remaining 45 mice were constructed as the ischemic stroke model. There were 40 mice who finally completed the modeling, and then they were randomly divided into the blank control group (GB0w), short-course administration group (GB1w), long-term administration group (GB2w), and long-term administration+antagonist group (GB2w+PRI-724), with 10 mice in each group. There was no drug intervention after MCAO in GB0w. The mice in GB1w were given ginkgolide B (10 mg/kg) 0.1 ml within 1 week after MCAO; in GB2w were given ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and in GB2w+PRI-724 were nasally fed ginkgolide B (10 mg/kg) 0.1 ml within 2 weeks after MCAO; and selective antagonist PRI-724 was given 3 h before administration of ginkgolide B on days 8 to 14. Neurological function scores, walking on rotor bar test scores, expression of transforming growth factor-β1 (TGF-β1), fibroblast growth factor 4 (FGF4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), Wnt, β-catenin, and glycogen synthase kinase-3β (GSK-3β) were compared among the groups.Results:Compared with the sham group, the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β in GB0w, GB1w, GB2w, and GB2w+ PRI-724 were increased, and the expressions of GSH-Px, SOD, TGF-β1, β-catenin, and Wnt were decreased (all P < 0.001). Compared with GB0w, the expressions of SOD, GSH-Px, TGF-β1, Wnt, and β-catenin were increased in GB1w, GB2w, and GB2w+PRI-724, and the expressions of MDA, TNF-α, IL-6, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB1w, the expressions of GSH-Px, SOD, TGF-β 1, Wnt, and β-catenin were increased in GB2w and GB2w+PRI-724, and the expressions of IL-6, TNF-α, MDA, FGF4, and GSK-3β were decreased (all P < 0.001). Compared with GB2w, the neural function score, walking on the stick test score, and expressions of IL-6, TNF-α, FGF4, MDA, and GSK-3β were increased in GB2w+PRI-724, while the expressions of GSH-Px, TGF-β1, SOD, Wnt, and β-catenin were decreased (all P < 0.001). Conclusions:Ginkgolide B can effectively improve the neurological function of ischemic stroke mice and may be related to the Wnt/β-catenin pathway.

【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL^-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL^-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

ObjectiveTo investigate the regulatory effects of Ginkgolide B on the biological characteristics of brain T cells and their interactions with glial cells during the recovery phase of ischemic stroke in mice. Methods36 adult C57BL/6 mice were randomly assigned to three groups: sham-operated group (Sham group), control group (PBS group), and Ginkgolide B treatment group (GB group). The Sham group underwent only sham surgeries, whereas the PBS and GB groups were subjected to a middle cerebral artery occlusion (MCAO) model using the filament method, followed by intranasal administration of an equivalent volume of either PBS or Ginkgolide B solution for 14 days post-injury. Neurological function changes were evaluated in all three groups using the rotarod test and a neurological scoring system. On day 15, single-cell sequencing was performed on fresh tissues from the brain injury areas, surrounding cortex, corpus callosum, and striatum of mice in the PBS and GB group to assess the biological characteristics of T cells and their subpopulations, and further explore the interactions and mechanisms among T cells, microglia, and oligodendrocytes. ResultsCompared with the Sham group, both PBS and GB group exhibited significant improvements in neurological scores and reduced pre-fall motor durations (P < 0.001). Compared with the PBS group, the GB group showed a downward trend in neurological scores and an upward trend in pre-fall motor durations on days 5, 10, and 15 post-ischemic brain injury, with a significant increase in pre-fall motor duration on day 15 (P < 0.05). Compared with the PBS group, the GB group exhibited a significant increase in T cell proliferative activity in the brain 15 days post brain injury (P < 0.05). The number of proliferative T cells and the levels of lipid metabolism were significantly elevated (P < 0.05), and there was a significant increase in extracellular matrix remodeling in all T cells (P < 0.05). Additionally, the interactions between T cells and both microglia and oligodendrocytes, as well as among the microglia themselves and between microglia and oligodendrocytes, were significantly enhanced in the GB group. This was primarily evident in the strengthened interactions between CD74 and macrophage migration inhibitory factor (MIF), as well as colony stimulating factor 1 receptor (CSF1R) and colony stimulating factor 1 (CSF1) (P < 0.05). However, the inflammatory levels of T cells showed no significant differences compared with the PBS group. ConclusionA mouse model of ischemic stroke can be successfully established by MCAO operation. Ginkgolide B may promote neurological recovery post-brain injury in mice by modulating the biological characteristics of T cells within the brain and their interactions with glial cells.

ObjectiveTo investigate rehabilitation competence among trainers and trainees whom participated in the training program entitled National Training Program of Shortage Rehabilitation Physicians (NTPSRP) using World Health Organization rehabilitation competency framework (RCF). MethodsBased on RCF, a questionnaire was developed and administrated through network using Questionnaire Star. All the trainers and trainees who participated in NTPSRP were investigated in September, 2023. ResultsA total of 911 subjects were collected from 27 provinces, including 426 trainers (teachers) and 485 trainees (students). The average age of the teachers was older, with more years of work experience and professional experience in rehabilitation medicine. The degree and professional title of the teachers was also higher. The overall internal consistency reliability of the questionnaire was good (Cronbach's α = 0.988), and all the internal consistency reliability in five fields was good (Cronbach's α > 0.9). The five dimensional structure of RCF in the results was consistent with the prior model established by RCF theory. The self-ratings of all physicians in the five fields were higher than the median level, and was higher in the teachers than in the students [(3.42±0.68) vs. (2.73±0.80), P < 0.001]. Gender and years of experience in rehabilitation medicine were independent factors for the total score of the questionnaire. The total self-rating of female students was 9.65 points lower than that of the male (95%CI 4.386 to 14.914); and one more year in rehabilitation medicine would increase 1.78 points in self-rating (95%CI 1.140 to 2.419). ConclusionThe structure and content of RCF can be used to evaluate the competence of rehabilitation physicians. The teachers and students of NTPSRP are eligible to RCF. RCF-based evaluation can be used to guide the development of continuing education courses for rehabilitation professionals.

Platelets play an important role in physiological and pathological activities such as thrombosis, inflammation and tumorigenesis. At present, the application of platelets in drug delivery systems is increasingly studied. Compared with traditional drug delivery systems, new drug delivery systems based on platelets and their derivatives can effectively improve the circulation time and selective accumulation, and reduce the occurrence of related immune reactions or off-target toxic and side effects. In this paper, the types and applications of platelet and its derivatives drug delivery systems were summarized in order to provide reference for platelet-related drug delivery research.

Tinnitus refers to the perception of abnormal sound in the absence of external sound stimulation. It can have an impact on a person's mood, memory, attention, and mental state, although the mechanism of tinnitus is still unclear. In recent years, the research on the central neural mechanism of tinnitus has attracted the attention of scholars.Functional magnetic resonance imaging （fMRI）,as an effective imaging technology, has been actively employed in this field. This paper provides a systematic summary of studies on the central neural mechanism of tinnitus by fMRI in recent years,revealed the changes of functional connections among tinnitus-related neural networks,such as auditory network,limbic system,default mode network and salience network. The central neural mechanism of tinnitus involves multiple networks that interact with each other. By understanding this mechanism, we hope to develop more targeted prevention and treatment strategies to help patients alleviate long-term tinnitus.
Humans ; Tinnitus/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Attention

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*

Red blood cells(RBCs), as the most abundant types of blood cells in the blood, have several advantages as a drug delivery system due to their ultra-long circulation half-life, good biocompatibility, and biodegradability. To date, a variety of RBCs-based drug delivery techniques have been developed for the treatment of infection diseases, cancers, chronic diseases, and autoimmune diseases. This review summarized the progress of RBCs related drug delivery systems, and discussed the advantages and disadvantages of different loading methods and their pre-clinical application progress, promoting the research and development of drug delivery.

【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) on the chemosensitivity of human breast cancer MCF-7 cell subcutaneous xenografts in nude mice and its mechanism. 【Methods】 The MCF-7 cells in exponential growth phase were collected and made into suspension cells at a density of 5×10⁷ cells/mL.Subsequently, the cells were inoculated subcutaneously in the right limb of 18 BALB/c-nu nude mice with 0.2 mL cells per mouse to establish subcutaneous xenograft.When the tumor volume reached about 100 mm³, they were randomly divided into chemotherapy group: doxorubicin 5 mg·kg^-1, once/week; chemotherapy + PolyCHb group: in addition to doxorubicin (chemotherapy group), PolyCHb 600 mg·kg^-1, 3 times/week; the control group: normal saline 90 mg·kg^-1, once/week; all were injected through tail vein continuously for 4 weeks.From the day of injection (d 0), the tumor volume of each group of nude mice was measured every 3 days, and the tumor growth curves were drawn accordingly.After 38 days, the tumor growth observation was completed.The tumor was removed and weighed to calculate the tumor inhibition rate.HE staining, immunohistochemistry and TUNEL method were used to observe the pathological changes of tumor tissue, detect the expression of HIF-1α, and detect tumor cell apoptosis respectively.The content of reactive oxygen species (ROS) of each group was determined by fluorescence staining. 【Results】 The tumor volume (mm³) of chemotherapy + PolyCHb group, chemotherapy group and the control group at day 38 were 196.35±103.45 vs 316.29±62.88 vs 519.42±177.33 (P<0.05), and the tumor inhibition rate (%) of chemotherapy + PolyCHb treatment group and chemotherapy group was 62.20 vs 39.11, respectively.HE staining and TUNEL detection showed that cell necrosis and apoptosis in the growth area of tumor tissue increased in chemotherapy + PolyCHb group.Immunohistochemistry and fluorescence staining showed that HIF-1α expression in chemotherapy + PolyCHb group decreased and reactive oxygen species (ROS) content increased. 【Conclusion】 PolyCHb increases the chemosensitivity of subcutaneous xenograft in nude mice with breast cancer, and its mechanism may be related to the increase of ROS in tumor tissue and the promotion of tumor cell apoptosis.

Objective:To investigate the clinical effect on ultrasound-guided vascular access-interventional therapy of hemodialysis in day surgery mode.Methods:Hemodialysis patients with vascular access dysfunction who underwent ultrasound-guided interventional therapy in the First Affiliated Hospital of Xi'an Jiaotong University from September 1, 2018 to October 31, 2020 were retrospectively analyzed. Demographic and clinical data were collected by electronic medical record system and telephone follow-up. Kaplan-Meier method was used to analyze the patency rate of vascular access.Results:A total of 421 cases of ultrasound-guided vascular access intervention were performed in 269 patients. The technical success rates of stenosis, chronic occlusion and acute occlusion lesion were 98.8%, 90.6% and 86.4%, respectively, and 406 cases (96.4%) of 246 patients were clinically successful. The postoperative brachial artery blood flow was 821(627, 1 029) ml/min, which was significantly higher than 309(202, 453) ml/min before the operation ( Z=-13.547, P<0.001). No serious complications occurred during and after the operation. At 6, 12, 18 and 24 months after operation, the primary patency rate was 74%, 59%, 48% and 45%, respectively, the assisted primary patency rate was 94%, 91%, 88% and 82%, and the secondary patency rate was 96%, 93%, 91% and 86%. Compared with the conventional inpatient surgery mode, the total cost of the day surgery mode was significantly reduced [12 067(10 051, 13 198) yuan vs 14 986(12 411, 20 643) yuan, Z=-13.185, P<0.001], and the hospital stay was significantly shortened [5.1(3.5, 6.9) h vs 73.4(31.6, 146.6) h, Z=-13.348, P<0.001]. Conclusion:It is safe and effective to perform interventional therapy for vascular access malfunction under ultrasound in day surgery mode, which can save cost and time of hospitalization, and can be carried out in hospitals with relevant conditions.