Objective To investigate the ameliorative effect of deferoxamine(DFO)on cognitive impairment in a rat model of type 1 diabetes mellitus(T1DM)and to elucidate the molecular mechanisms underlying cerebral iron overload in T1DM rats.Methods Thirty-six healthy male SD rats(weighing 180～250 g)were randomly assigned into a blank control group(Ctrl),a T1DM model group and a DFO group,with 12 rats in each group.A single dose of 65 mg/kg streptozotocin(STZ)was intraperitoneally injected to the rats to establish a T1DM model,and those with fasting blood glucose≥16.7 mmol/L at 3 d later were designated as the T1DM group.Intracerebroventricular administration of DFO(5 μg/kg·d)was given to the DFO group for 28 consecutive days since 21 d after STZ injection.Morris water maze test was carried out to assess the spatial learning and memory abilities.Nissl staining and immunofluorescence assay were applied to observe neuronal morphology and number in the hippocampus and cortex.The iron content in the hippocampus was measured with inductively coupled plasma mass spectrometry(ICP-MS).The expression levels of iron metabolism related proteins were detected with Western blotting.Results In the T1DM group,significant declines in learning and memory abilities(P<0.01)and impaired neuronal morphology and reduced neuronal counts in the hippocampal CA1 region(P<0.01),CA3 region(P<0.01),and cortex(P<0.05)were observed when compared with those in the Ctrl group.ICP-MS analysis showed a marked increase in the hippocampal iron content in the T1DM group(P<0.01).Western blot results demonstrated that T1DM rats exhibited obviously up-regulated expression of iron storage proteins FTH and FTL in both the hippocampus(P<0.01,P<0.05)and the cortex(P<0.05,P<0.01),enhanced expression of iron import protein DMT1 in both the hippocampus and the cortex(P<0.05),while decreased expression of iron export protein FPN1 in the hippocampus(P<0.01)and the cortex(P<0.05).DFO treatment significantly ameliorated all above abnormalities.Conclusion The declines in learning and memory in T1DM rats are closely associated with neuronal damage induced by cerebral iron overload.Iron import protein DMT1 and export protein FPN1 jointly regulate cerebral iron content in T1DM rats.DFO reduces brain iron levels and mitigates iron overload-mediated neuronal injury by modulating the expression of DMT1 and FPN1.

BACKGROUND:Asperosaponin Ⅵ has good osteogenic effects,but its ability to promote cellular osteogenesis under hypoxia environment is not yet clear.OBJECTIVE:To investigate the effect and potential mechanism of Asperosaponin Ⅵ on osteogenic differentiation of MC3T3-E1 cells under hypoxia environment.METHODS:MC3T3-E1 cells were divided into three groups.Cells in the control group were cultured in a complete medium under normoxic conditions(volume fraction of 21％O2);cells in the hypoxia group were cultured in the complete medium under hypoxia conditions(volume fraction of 0.5％O2);and cells in the Asperosaponin Ⅵ group were cultured in the complete medium containing Asperosaponin Ⅵ under hypoxia conditions(volume fraction of 0.5％oxygen).After 24 hours of culture,cell counting kit-8 method and EdU staining were used to detect cell proliferation activity,TUNEL staining and western blot assay were performed to detect cell apoptosis,and flow cytometry was used to detect intracellular reactive oxygen species levels and cell cycle distribution.Each group of cells was cultured in an osteogenic induction medium containing 1×10-5,1×10-6,and 1×10-7 mol/L Asperosaponin Ⅵ under hypoxia conditions for 7 days.The optimal concentration of Asperosaponin Ⅵ for intervention was identified using alkaline phosphatase staining under optical microscopy.Western blot was used to detect the expression of bone morphogenetic protein 2,osteopontin,and PI3K/AKT signaling axis-related proteins.RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation ability of MC3T3-E1 cells decreased under hypoxia conditions.1×10-6 mol/L Asperosaponin Ⅵ could significantly improve the cell proliferation ability under hypoxia conditions and reduce cell apoptosis.(2)Compared with the hypoxia group,the Asperosaponin Ⅵ group showed a decrease in intracellular reactive oxygen species and a significant increase in the proportion of cells in the S phase.(3)Compared with the hypoxia group,the cell morphology in the 1×10-6 mol/L Asperosaponin Ⅵ group was elongated,with more protrusions and darker alkaline phosphatase staining.(4)Compared with the hypoxia group,the expression of bone morphogenetic protein 2 and osteopontin increased in the Asperosaponin Ⅵ group,while the expression of p-PI3K and p-AKT proteins decreased.These findings indicate that under hypoxia conditions,Asperosaponin Ⅵcan promote osteogenic differentiation of MC3T3-E1 cells,possibly by regulating the PI3K/AKT pathway.

BACKGROUND:Asperosaponin Ⅵ has good osteogenic effects,but its ability to promote cellular osteogenesis under hypoxia environment is not yet clear.OBJECTIVE:To investigate the effect and potential mechanism of Asperosaponin Ⅵ on osteogenic differentiation of MC3T3-E1 cells under hypoxia environment.METHODS:MC3T3-E1 cells were divided into three groups.Cells in the control group were cultured in a complete medium under normoxic conditions(volume fraction of 21％O2);cells in the hypoxia group were cultured in the complete medium under hypoxia conditions(volume fraction of 0.5％O2);and cells in the Asperosaponin Ⅵ group were cultured in the complete medium containing Asperosaponin Ⅵ under hypoxia conditions(volume fraction of 0.5％oxygen).After 24 hours of culture,cell counting kit-8 method and EdU staining were used to detect cell proliferation activity,TUNEL staining and western blot assay were performed to detect cell apoptosis,and flow cytometry was used to detect intracellular reactive oxygen species levels and cell cycle distribution.Each group of cells was cultured in an osteogenic induction medium containing 1×10-5,1×10-6,and 1×10-7 mol/L Asperosaponin Ⅵ under hypoxia conditions for 7 days.The optimal concentration of Asperosaponin Ⅵ for intervention was identified using alkaline phosphatase staining under optical microscopy.Western blot was used to detect the expression of bone morphogenetic protein 2,osteopontin,and PI3K/AKT signaling axis-related proteins.RESULTS AND CONCLUSION:(1)Compared with the control group,the proliferation ability of MC3T3-E1 cells decreased under hypoxia conditions.1×10-6 mol/L Asperosaponin Ⅵ could significantly improve the cell proliferation ability under hypoxia conditions and reduce cell apoptosis.(2)Compared with the hypoxia group,the Asperosaponin Ⅵ group showed a decrease in intracellular reactive oxygen species and a significant increase in the proportion of cells in the S phase.(3)Compared with the hypoxia group,the cell morphology in the 1×10-6 mol/L Asperosaponin Ⅵ group was elongated,with more protrusions and darker alkaline phosphatase staining.(4)Compared with the hypoxia group,the expression of bone morphogenetic protein 2 and osteopontin increased in the Asperosaponin Ⅵ group,while the expression of p-PI3K and p-AKT proteins decreased.These findings indicate that under hypoxia conditions,Asperosaponin Ⅵcan promote osteogenic differentiation of MC3T3-E1 cells,possibly by regulating the PI3K/AKT pathway.

Objective: To investigate the clinical manifestations, pathological features, and treatment of oral and maxillofacial pyogenic granulomas induced by camrelizumab. Methods: A case of pyogenic granuloma of the gums and lips caused by camrelizumab was reported along with a literature review. Results: After 4 months of treatment with camrelizumab for liver cancer, the patient developed systemic reactive capillary hyperplasia (RCH), followed by multiple masses on the lower lip and gingiva. After periodontal therapy, the masses on the lower lip and the gingiva were removed, and camrelizumab administration was stopped. The pathological result was gingival pyogenic granuloma/granulomatous hemangioma. No new masses were found in the oral cavity during postoperative follow-up. A review of the literature showed that RCH is the most common adverse drug reaction to camrelizumab but it occurs infrequently in the oral cavity. At present, the etiology of RCH has not been clarified, but the research has shown that camrelizumab may trigger tissue proliferation into hemangiomas by activating vascular endothelial cells, and the combined use of camrelizumab is safer than single use. RCH is self-limiting and most cases resolve spontaneously after discontinuation of the drug. If the mass causes dysfunction, surgical excision is feasible. Conclusion Camrelizumab can cause oral and maxillofacial reactive capillary hyperplasia complicated by pyogenic granuloma.

Objective:To analyze the clinical characteristics of elderly patients with papillary thyroid cancer(PTC)by age grouping.Methods:The patients were divided into three groups according to age at diagnosis: old(≥60 years, 90 cases), middle(40-59 years, 359 cases)and young patients(<40 years, 203 cases). The clinical data of 652 patients with PTC who were admitted to the Department of Thyroid Surgery of Beijing Hospital from December 2019 to December 2021 were retrospectively analyzed.The patients were divided into elderly group(≥60 years old, 90 cases), middle-aged group(40-59 years old, 359 cases)and young group(<40 years old, 203 cases). The clinical characteristics, ultrasound characteristics and invasion-related factors of patients in different groups were analyzed by statistical methods.Results:Compared with the young and middle-aged group, the elderly patients with PTC had a higher proportion of microcarcinoma(75.6%, 75.2%, 61.4%, χ2=13.054, P=0.001), less cervical lymph node metastasis(24.4%, 34.3%, 58.1%, χ2=41.650, P<0.001), and lower proportion of metastatic lymph nodes(0.08, 0.14, 0.24, χ2=40.618, P<0.001). There was no significant difference in tumor location and extra glandular invasion among the three age groups(35.56%, 36.2%, 38.4%, χ2=0.959, P=0.545). Conclusions:Compared with the young and middle-aged groups, PTC showed low invasiveness in the elderly population.In addition to surgical treatment, for elderly patients with low-risk clinical characteristics, it is worth performing a further study on whether careful observation or palliative treatment can be selected after comprehensive evaluation.