BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.

Objective To explore the mechanism of Bushen Zhupai Decoction in treating ovarian fibrosis in polycystic ovary syndrome(PCOS)model rats based on IL-17/TRAF6/NF-κB signaling pathway.Methods Totally 60 SPF grade female SD rats were randomly divided into blank group,model group,Yousiyue group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.The PCOS model was replicated by gavage of 1 mg/kg letrozole for 21 days.The Yousiyue group was given a 10 mg/kg solution of drospirenone ethinylestradiol tablets by gavage,TCM low-,medium-and high-dosage groups were given 8.82,17.64 and 35.28 g/kg of Bushen Zhupai Decoction by gavage,once a day for 28 consecutive days.HE and Masson staining were used to observe the morphology of ovarian tissue and ovarian fibrosis,the contents of serum IL-17,IL-18 and IL-1β were detected by ELISA,the mRNA expression of IL-17,TRAF6,NF-κB p65 and TGF-β1 in ovarian tissue were determined by RT-qPCR,the protein expression of TRAF6,NF-κB p65,TGF-β1,α-SMA,E-cadherin and the positive expression of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue were detected by Western blot and immunohistochemical staining respectively.Results Compared with the blank group,the body mass,ovarian mass and ovarian index significantly increased of rats in model group,with follicular cystic dilation,thinning of granulosa cell layer,and significant increase in fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly increased(P<0.01),the expressions of IL-17,TRAF6,NF-κB p65,TGF-β1 mRNA and IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA proteins significantly increased(P<0.01,P<0.05),the expression of E-cadherin protein significantly decreased(P<0.01).Compared with the model group,the ovarian index of rats in Yousiyue group and TCM medium-and high-dosage groups significantly decreased(P<0.01,P<0.05),the rats in TCM high-dosage group showed dominant follicles,increased thickness of granulosa cell layer,and significantly reduced fibrosis positive range(P<0.01),the serum contents of IL-17,IL-18 and IL-1β significantly decreased in Yousiyue group and TCM low-,medium-and high-dosage groups(P<0.01),the mRNA expressions of IL-17,TRAF6,NF-κB p65,TGF-β1,and the protein expressions of IL-17RA,TRAF6,NF-κB p65,TGF-β1 and α-SMA in ovarian tissue significantly decreaed in TCM high-dosage group(P<0.01,P<0.05),the expression of E-cadherin protein significantly increased(P<0.01).Conclusion Bushen Zhupai Decoction can decrease the body mass,improve the ovarian index,decrease the expressions of inflammatory factors and improve the status of ovarian fibrosis in PCOS rats.The mechanism may be related to the regulation of IL-17/TRAF6/NF-κB signaling pathway.

Objective:To investigate the effects of spinal cord injury(SCI)on neuropathic pain(NP)and cognitive dysfunction in mice,as well as the activation of neurons in the anterior cingulate cortex(ACC),in order to provide experimental evidence for the connection between NP and cognitive dysfunction following SCI.Methods:Ten 8-week-old male C57BL/6J mice were used to prepare a model of spinal cord hemisection(SCI).Pain behavior and cognitive function of mice after SCI were assessed using von Frey,thermal stimulation,and Morris water maze behavioral experi-ments.Immunofluorescence staining were used to analyze the expression of c-Fos and GAD67/VGLUT2 positive cells in the anterior cingulate cortex(ACC)of the SCI model mice.Results:Compared with the Sham group,the SCI group of mice showed a significant decrease in mechanical threshold and thermal pain threshold(P＜0.05).The Morris water maze results indicated a significantly prolonged escape latency(P＜0.05)and a significant reduction in the use of search strategies for locating the hidden platform.Immunofluorescence results showed a significant increase in the num-ber of c-Fos positive cells in the ACC(P＜0.05),which were mainly co-labeled with excitatory neuron marker VGLUT2 positive cells.Conclusion:SCI leads to abnormal pain behavior and cognitive dysfunction in mice,and it induces the activation of neurons in the ACC,with a predominant activation of excitatory neurons.This study provides morphological evidence for the involvement of excitatory neurons in the ACC in the comorbidity of NP and cognitive impairment following SCI.

Objective:To investigate the effects of spinal cord injury(SCI)on neuropathic pain(NP)and cognitive dysfunction in mice,as well as the activation of neurons in the anterior cingulate cortex(ACC),in order to provide experimental evidence for the connection between NP and cognitive dysfunction following SCI.Methods:Ten 8-week-old male C57BL/6J mice were used to prepare a model of spinal cord hemisection(SCI).Pain behavior and cognitive function of mice after SCI were assessed using von Frey,thermal stimulation,and Morris water maze behavioral experi-ments.Immunofluorescence staining were used to analyze the expression of c-Fos and GAD67/VGLUT2 positive cells in the anterior cingulate cortex(ACC)of the SCI model mice.Results:Compared with the Sham group,the SCI group of mice showed a significant decrease in mechanical threshold and thermal pain threshold(P＜0.05).The Morris water maze results indicated a significantly prolonged escape latency(P＜0.05)and a significant reduction in the use of search strategies for locating the hidden platform.Immunofluorescence results showed a significant increase in the num-ber of c-Fos positive cells in the ACC(P＜0.05),which were mainly co-labeled with excitatory neuron marker VGLUT2 positive cells.Conclusion:SCI leads to abnormal pain behavior and cognitive dysfunction in mice,and it induces the activation of neurons in the ACC,with a predominant activation of excitatory neurons.This study provides morphological evidence for the involvement of excitatory neurons in the ACC in the comorbidity of NP and cognitive impairment following SCI.

Objective:To elucidate the effects of different morphologies and sizes of micro/nanomaterial on luminescence properties.Methods:Lu2O3:Eu3+micro-/nanocrystals with different morphologies were synthesized hydrothermally,and the effects of precursor concentration,reaction time,pH,and alkali source on morphology and photoluminescence were investigated.Products were calcined and then characterized for morphology and photoluminescence.Spectra were collected with 250 nm excitation,focusing on the O2-→Eu3+charge-transfer band(CTB)and Eu3+f-f transitions.Results:The use of NaOH,aqueous ammonia,or triethylamine yielded monodisperse square nanosheets after calcination,while the use of urea produced monodisperse and uniform nanospheres.Fluorescence measurements showed a strong CTB near 250 nm.Under 250 nm excitation,the emission comprised multiple peaks,with the the strongest being the 5D?→7F2 hypersensitive transition at 614 nm.Conclusions:In the hydrothermal system,alkali source and reaction parameters provide significant control over the morphology and size of Lu2O3:Eu3+micro-/nanocrystals.The morphology-dependent emission is dominated by red light at 614 nm(5D?→7F).

Objective:To comprehensively assess the nutritional literacy among family caregivers of elderly patients with chronic heart failure (CHF), so as to provide reference for developing clinical nutrition management strategies for elderly CHF patients.Methods:This study was a descriptive qualitative research. From February to March 2025, purposive sampling was used to select 17 family caregivers of elderly CHF patients at Affiliated Hospital of Yangzhou University as research subjects for semi-structured interviews. The data was analysed using a directed content analysis approach.Results:Three themes and nine subthemes were identified, including functional nutrition literacy (lack of disease-related nutrition knowledge, difficulty in knowledge transformation and utilization, and barriers to voluntary nutritional adherence), interactive functional literacy (limited channels for accessing nutrition information, broken healthcare services, insufficient motivation for proactive communication, and demand for professional dietary guidance), and critical nutrition literacy (challenges in distinguishing information authenticity, reliance on inherent cognition for evaluation) .Conclusions:Family caregivers of elderly patients with CHF commonly lack relevant nutritional knowledge. Healthcare providers should attach importance to the education of nutrition knowledge and skills for family caregivers, establish a multidimensional nutrition education system, develop personalized nutrition guidance plans, and integrate the family-community-medical collaborative support network to systematically strengthen caregivers' understanding of disease nutrition management for elderly CHF patients and enhance their compliance with nutrition care practices.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.