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【Objective】 To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. 【Methods】 CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. 【Results】 When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P<0.01). The results of H&E staining showed that the PL MNs group had fewer inflammatory cell infiltrates and bleeding spots. The number of fibroblasts and new microvascular in the control group was worse than that in the PL MNs group and the PL smear group. The results of immunohistochemistry indicated that the expression of pro-inflammatory factor IL-6 decreased, while anti-inflammatory factor TGF-β and angiogenesis index CD31 increased in the PL MNs group, which were significantly different from those in the other three groups (P<0.01). 【Conclusion】 The PL MNs prepared in this experiment have good mechanical properties, which has a positive effect on the wound healing of diabetic mice, and provides a new idea for diabetic wound healing.
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【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) in chemoimmunotherapy for breast cancer in mice. 【Methods】 A 4T1 breast cancer in situ tumor model was established, and 15 mice were randomly divided into 3 groups: blank group: no intervention; Control group: doxorubicin + PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg-1 once a week and PD-1 inhibitor 12.5 mg·kg-1 once a week; Experimental group: DOX+ a-PD-1+ PolyCHb, the usage of DOX and a-PD-1 was the same as above, PolyCHb: PolyCHb 600 mg·kg-1 was injected into the tail vein, three times a week; The administration period was 4 weeks. During the administration, the tumor volume was recorded 3 times per week, the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated. The mice were killed on the 29th day, and the tumor was removed and weighed to calculate the tumor inhibition rate. Immunofluorescence, HE staining, TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α, observe the pathological changes of tumor tissue, detect the apoptosis of tumor cells, and detect the expression of tumor proliferation index Ki67. 【Results】 Compared with the blank group and the control group, the tumor volume in the experimental group decreased significantly (P<0.05) and the tumor inhibition rate (%) increased significantly (P<0.05). The content of HIF-1α in tumor tissue in experimental group decreased (P<0.05). In the experimental group, the growth area of tumor tissue decreased, accompanied by the increase of necrosis area; The positive rates (%) of apoptosis in tumor tissues of blank group, control group and experimental group were 18.79±0.62, 20.68±1.19 and 41.65±2.99 respectively (F=135.2, P<0.001). In addition, the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group (P<0.05). 【Conclusion】 PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model, and the mechanism may be related to the decrease of HIF-1α expression, the promotion of apoptosis and the inhibition of cell proliferation.
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【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.
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Most solid tumors suffer from inadequate blood perfusion and oxygenation, leading to a hypoxic microenvironment that accelerates tumor progression and adversely impacts prognosis. Thus, improving oxygenation in tumor tissues is crucial for enhancing the sensitivity and efficacy of tumor therapy. Hemoglobin-based oxygen carriers (HBOCs), as a type of oxygen-carrying nanoparticles, can not only carry and release oxygen but also reach the small blood vessels of obstructive microcirculation to deliver oxygen for anoxic tissues and organs, which are difficult for normal red blood cells to pass through. Studies have demonstrated that the application of HBOCs as a potential nanoscale efficient oxygen carrier in tumor therapy can enhance tissue oxygenation and hold great promise for applications in tumor therapy.This review summarizes the impact of hypoxia in tumors and highlights the progress and potential mechanisms of using HBOCs in tumor radiotherapy, chemotherapy, new kinetic therapy and immunotherapy.
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Objective@#To analyze the association between short term PM 2.5 exposure and high blood pressure in adolescents and its modification effect of overweight and obesity, and to provide a reference for the refined management of students physical health and the scientific prevention and controlling of air pollution.@*Methods@#A total of 148 956 junior high school students and senior high school students who passed the annual physical examination data of middle school students in Beijing from 2017 to 2018 were selected; The inverse distance weighted interpolation method was used to get the meteorological elements and air quality of the research area; Linear mixed effect model was used to estimate the cumulative lag effect of short term PM 2.5 exposure on systolic and diastolic blood pressure within 7 days, and analyze the modification effect of overweight and obesity on the association between short term PM 2.5 exposure and high blood pressure in adolescents.@*Results@#From September 1, 2017 to June 30, 2018, the average concentration of PM 2.5 was (56.53±45.85)μg/m 3; The detection rate of overweight and obesity was 34.22%, and the detection rate of high blood pressure was 8.03%. The cumulative lag effect of PM 2.5 on systolic blood pressure in overweight and obesity group was the largest at lag07, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.05,95% CI =1.03-1.07); the cumulative lag effect of PM 2.5 on systolic blood pressure in non overweight and obese group was the largest at lag05, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.04,95% CI =1.02-1.06). Short term exposure to PM 2.5 did not affect the high diastolic blood pressure in adolescents. Overweight and obese adolescents were more susceptible to high blood pressure caused by short term PM 2.5 exposure within 3 days of cumulative lag (lag01-lag03).@*Conclusion@#The short term exposure of PM 2.5 has a significant positive correlation with adolescent blood pressure, and shows a lag effect. Overweight and obese adolescents have higher blood pressure after PM 2.5 short term exposure.
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Objective@#To analyze the relationship between short term exposure of PM 2.5 and the vital capacity of children and adolescents and the modification effect of overweight and obesity, and to provide a scientific reference for appropriate outdoor activities and strengthening prevention of air pollution.@*Methods@#A total of 1 036 273 students who qualified in the annual health examination data of primary and secondary school students in a city from 2017 to 2018 were selected; the meteorological factors and air quality of the study area were obtained by inverse distance weighted interpolation method; the generalized linear mixed model was used to estimate the individual lag effect and average lag effect of PM 2.5 short term exposure on lung capacity with in 7 days, and to analyze the modification effect of overweight and obesity on the relationship between short term PM 2.5 exposure and vital capacity in children and adolescents.@*Results@#From September 1, 2017 to June 30, 2018, the average PM 2.5 concentration in this city was 66.36 μg/m 3, the detection rate of overweight and obesity was 33.38%, and the average lung capacity was (2 286.72±956.77)mL. The single lag effect of PM 2.5 on vital capacity was the biggest when lag6, the average daily PM 2.5 concentration increased by 10 μg/m 3 and the decrease of vital capacity of children and adolescents by 2.81(95% CI =2.60-3.03)mL. The average lag effect of PM 2.5 on lung capacity was the largest when lag07, the average concentration of PM 2.5 sliding was significantly correlated with the decrease of lung capacity of children and adolescents by 5.82(95% CI =5.37-6.27)mL every 10 μg/m 3 increase. The prevalence of PM 2.5 short term exposure to pulmonary capacity decreased in overweight and obese children and adolescents was higher ( P ＜0.01).@*Conclusion@#The short term exposure of PM 2.5 has a significant negative correlation with the lung capacity of children and adolescents, and there is a lag effect. The decrease of the vital capacity of overweight and obese children and adolescents after PM 2.5 short term exposure is more significant.