BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1％Zn2+poly(vinylidene fluoride),1％Mg2+poly(vinylidene fluoride),1％Zn2++1％Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)％,(0.149±0.020)％,(0.466±0.018)％,and(0.037±0.018)％,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

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Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95％CI:1.532～2.499),length of ICU stay (P=0.000,OR=2.561,95％CI:1.728～3.794),number of operations (P=0.015,OR=1.814,95％CI:1.124～2.927),spinal fixation (P=0.004,OR=0.370,95％CI:0.189～0.724),restrictive position (P=0.000,OR=21.269,95％CI:5.276～85.740),platelet count (P=0.000,OR=1.553,95％CI:1.236～1.951),D-dimer level (P=0.000,OR=1.600,95％CI:1.376～1.860)and prothrombin time (P=0.025,OR=2.756,95％CI:1.138～6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.

BACKGROUND:Due to the unstable drug release rate of uniaxial bone scaffolds,multi-structure composite printing methods have been sought in and outside China in recent years.Currently,coaxial drug-loaded bone scaffolds,which combine drug-loaded sustained release system with bone transplantation and repair technology,not only replace the defective bone after implantation,but also release drugs slowly,providing a microenvironment conducive to bone formation at the implant site. OBJECTIVE:To explore and assess the in vitro antibacterial properties of uniaxial and coaxial minocycline hydrochloride bone scaffolds. METHODS:Rapid prototyping technology was used to prepare uniaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,uniaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,coaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,and coaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,respectively,which were named S1,S2,T1 and T2.The morphology,porosity,degradation performance,in vitro sustained-release performance and cytotoxicity of scaffolds were characterized.Four kinds of bone scaffolds were immersed in PBS to prepare the extracts at different time points(1,3,5,7,14,21,and 28 days).The qualitative filter paper was placed into the extract for 24 hours.The filter paper was co-cultured with Porphyromonas gingivalis and Fusobacterium nucleatum for 72 hours.The bacteriostatic effect of four groups of scaffolds was detected by the agar diffusion method. RESULTS AND CONCLUSION:(1)Scaffold characterization:Four groups of scaffolds were well formed.The surface of micro-wires in the S1 and S2 groups was dense and smooth,and the surface of micro-wires in the T1 and T2 groups was rough.Porosity was between 40%-47%and met the requirements of bone scaffolds.Compared with the S2 group,sustained release time was longer in the T2 group.The sustained release concentration of the drug was between 1-10 μg/mL for a long time,which was more conducive to bacteriostasis and osteogenesis.After 10 weeks of immersion in PBS in vitro,the degradation rate of the coaxial printed bone scaffold was faster than that of the corresponding uniaxial printed bone scaffold,and the degradation rate of the coaxial loaded bone scaffold was lower than that of the coaxial non-loaded bone scaffold.The four groups of scaffold extracts were co-cultured with osteoblasts respectively.CCK-8 assay displayed that the cell proliferation rate was greater than 75%,which met the requirements of biocompatibility.(2)In vitro antibacterial effect:S1 and T1 did not have antibacterial activity.S2 and T2 had an obvious antibacterial effect.Under the extraction solution on day 28,the diameter of Porphyromonas gingivalis and Fusobacterium nucleatum inhibition zone in the S2 group was smaller than that in the T2 group(P<0.05).(3)These findings exhibit that hydroxyapatite/silk fibroin-polyvinyl alcohol scaffolds with coaxial minocycline have good physical properties and bacteriostatic properties.

BACKGROUND:Polyvinylidene fluoride(PVDF)with piezoelectric properties,good biocompatibility and nontoxicity make it a suitable candidate for periosteal repair. OBJECTIVE:To evaluate the cytotoxicity of PVDF bionic periosteum by electrospinning with zinc and magnesium ions in vitro. METHODS:Pure PVDF,zinc-doped PVDF,magnesium-doped PVDF and Zinc-magnesium ion PVDF piezoelectric bionic periosteum were prepared by electrospinning technology,respectively.They were named PVDF,PVDF-Zn,PVDF-Mg and PVDF-Zn-Mg,in which the mass fraction of zinc and magnesium ions were all 1%.Osteoblasts and vascular endothelial cells were co-cultured with four groups of bionic periosteum.Cell compatibility of bionic periosteum was determined by alkaline phosphatase staining,CD31 immunofluorescence staining,and scanning electron microscopy. RESULTS AND CONCLUSION:(1)Osteoblasts:Alkaline phosphatase staining after 7 days of culture showed that the PVDF-Zn group secreted more alkaline phosphatase than the other three groups.Under a scanning electron microscopy,after 1 day of culture,the cells had a certain spread on the surface of PVDF-Mg and PVDF-Zn-Mg bionic periosteum,and the pseudopod extended to all sides.On day 3,the cell edge of each group extended pseudopods to the material.By days 5 and 7,the cells were fully spread,well grown and firmly covered the surface of the fibers,and the cellular pseudopods extended around and into the interstitial space of the fibers.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed an increasing trend over time and the relative proliferation rate of cells at 1,3,5,and 7 days was≥75%,and the cytotoxicity was≤grade 1.(2)Vascular endothelial cells:CD31 immunofluorescence staining for 3 days showed that the cells adhered and spread well on the bionic periosteum of each group and connected with each other,and the number of cells in the PVDF-Zn-Mg group was more than that in the other three groups.Under scanning electron microscope,the cells began to adhere to the surface of each group of fibers after 1 and 3 days of culture.On day 5,the cells were well spread on the surface of the fibers and extended obvious pseudopods.On day 7,the cells on the PVDF-Mg and PVDF-Zn-Mg bionic periosteum grew in multiple layers and extended the pseudopod into the fibrous void.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed a downward trend over time,and the relative proliferation rate of cells at 1,3,5 and 7 days was≥125%,and the cytotoxicity was grade 0.(3)The results showed that Zn-Mg electrospun PVDF piezoelectric bionic periosteum had good cytocompatibility.

Objective:To evaluate the risk factors for pulmonary embolism in patients with spinal injury.Methods:Literature on risk factors for pulmonary embolism after spinal injury was searched on CNKI, Wanfang database, VIP Chinese Science, PubMed, Embase, Cochrane Library, Up to Date databases from inception through November 2023. A Meta-analysis was performed with the software of RevMan 5.4 after two researchers screened the literature independently according to the inclusion and exclusion criteria, extracted the data and evaluated their quality. Correlations of gender, age, surgical duration, intervertebral disc fusion, body mass index, comorbidity, medicine prophylaxis, deep venous thrombosis (DVT) history, and length of hospital stay with the incidence of pulmonary embolism in patients with spinal injury were evaluated.Results:A total of 10 studies were enrolled, including 2 prospective cohort studies and 8 cross-sectional studies. The total sample size was 401 698 patients, with 525 in the pulmonary embolism group and 401 173 in the non-pulmonary embolism group. The Meta analysis showed that gender ( OR=1.59, 95% CI 1.20, 1.97), age ( OR=1.58, 95% CI 1.19, 2.10), surgical duration ( OR=2.56, 95% CI 1.84, 3.56), DVT history ( OR=15.84, 95% CI 1.88, 133.25) and length of hospital stay ( OR=1.08, 95% CI 1.07, 1.09) were statistically significantly correlated with the incidence of pulmonary embolism in patients with spinal injury ( P<0.01), while intervertebral fusion, body mass index, comorbidity, and medicine prophylaxis were not correlated with the incidence of pulmonary embolism ( P>0.05). Conclusion:Gender, age, surgical duration, DVT history and length of hospital stay are risk factors for pulmonary embolism in patients with spinal injury.

【Objective:】 To construct a questionnaire on medical students’ cognition level of public health ethics, and to provide a scientific and objective evaluation tool for understanding the cognitive level of medical students on public health ethics. 【Methods:】 Based on the literature review and focus group discussion, the initial questionnaire was constructed. The Delphi method was used to conduct three rounds of correspondence with 12 experts, and the final questionnaire was drafted. And exploratory factor analysis and internal consistency were used to evaluate the questionnaire. 【Results:】 In the three rounds of correspondence, the enthusiasms of experts were all 100%, the authority coefficients were all 0.84, the coefficients of variation were 0~0.32, 0~0.26, 0~0.12, respectively, and the coordination coefficients were 0.206, 0.163, and 0.250, respectively (all P<0.05). The analysis of the items showed that the critical ratio values and related coefficients of the questionnaire items were statistically different. The structural validity analysis showed that the cumulative variance contribution rate of the extracted two common factors was 61.015%. The intrinsic consistency reliability analysis showed that the questionnaire Cronbach’s coefficient was 0.956. Finally, the questionnaire of 26 items was formed, including two dimensions: knowledge of public health ethics and application of public health ethics. 【Conclusion:】 The questionnaire on medical students’ cognition level of public health ethics is reliable and has good reliability and validity, and can be used as a tool for medical students’ public health ethics cognition level.

Background Lead (Pb) exposure impairs cognitive functions of children. Whether Pb exposure in different developmental stages induces long-term cognitive impairment, and whether chelation therapy could mitigate the cognitive impairment is rarely reported. Objective This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages (breastfeeding, weaning, and early puberty periods) on mouse short-term and long-term cognitive functions. Methods C57BL/6 male mice in breastfeeding period, weaning period, and early puberty period (postnatal day 2, 21, and 41; PND 2, PND 21, and PND 41, n=30, respectively) were randomly divided into control, Pb exposure, and Pb+dimercaptosuccinic acid (DMSA) treatment groups (n=10 in each group). The control groups received standard food and deionized water. The Pb exposure mice received standard food and free drinking water containing Pb acetate (0.1% for dams, and 0.05% for pups). After receiving Pb acetate for 19 d, the Pb+DMSA treatment groups were given 1 mmol·kg⁻¹·d⁻¹ DMSA for 6 d with gastric infusion. Whole blood Pb levels were measured after DMSA treatment on experimental day 25. The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79, as well as target quadrant time and times of platform-crossing on PND 80. Hippocampal long-term potentiation of field excitatory postsynaptic potential (fEPSP) of mice on PND 365 was induced to demonstrate the effects on long-term cognitive function. Results The blood Pb levels among the Pb, Pb+DMSA, and control groups were statistically different for each developmental stage (F_{breastfeeding period}=43.47, F_{weaning period}=228.6, F_{early period of puberty}=274.2, all P<0.001). Compared to the counterpart control groups, blood Pb levels of the pb exposure groups (386.4, 265.0, and 178.1 μg·L⁻¹ in breastfeeding period, weaning period, and early puberty period, respectively) were significantly higher for all stages. After the chelation therapy, the blood Pb significantly decreased for all stages (28.68, 47.29, and 20.93 μg·L⁻¹ in the three periods, respectively, all P<0.001) and the Pb levels of the mice exposed in the breastfeeding period decreased most (by 92.58%, 82.15%, and 88.25% in the three periods, respectively, P<0.01). In the water maze task, the mice exposed to Pb in the breastfeeding period had a gentler decrease in escape latency (from 54.20 s on day 1 to 30.54 s on day 5, by 43.65 % decrease) than the control group (from 32.44 s on day 1 to 15.20 s on day 5, by 53.14 % decrease) (P<0.01) and a significant decrease in target quadrant time (P<0.05). After the chelation therapy, the escape latency of the DMSA-treated mice in the breastfeeding period (from 40.94 s on day 1 to 20.87 s on day 5, by 48.99 % decrease) was steeper than that of the Pb-exposed mice (P<0.05). The differences in the escape latency, target quadrant time, and times of platform-crossing were not significant between the Pb-exposed mice and the control mice in the weaning period and early period of puberty (all P>0.05). After the chelation therapy, such differences were also not significant compared with before therapy. Due to the small sample size, data were merged for different developmental stages in the long-term potentiation test. The amplitudes of fEPSP induced in the control, Pb-exposed, and DMSA treatment groups were significantly different (F_groups=212.2, F_time=11.36. P<0.001). The average fEPSP amplitude induced in the last 10 min recorded in the hippocampal slices in the Pb exposure group was significantly lower than that in the control group (P<0.05). After the DMSA treatment, no significant differences were observed in the fEPSP amplitudes between the Pb exposure group and the DMSA treatment group (P>0.05). When observing the fEPSP data by developmental stages, the fEPSP amplitude in the breastfeeding Pb-exposure group was 27.2% lower than that of the breastfeeding control group, while such changes were not obvious in the weaning period or in the early period of puberty. The fEPSP amplitude in breastfeeding DMSA treatment group was 44.3% higher than that of the breastfeeding Pb exposure group, while such changes were not observed in the weaning period or in early period of puberty. Conclusion Pb exposure during different developmental stages, especially in breastfeeding period, could affect short-term and long-term cognitive functions of mice. The harmful effects may be partially reversed by DMSA chelation therapy, especially being treated in breastfeeding period.

Objective To analyze the correlation between intestinal flora changes and neonatal necrotizing enterocolitis (NEC)through 16S rRNA metagenomic sequencing and bacterial culture. Methods From September 2018 to March 2019, 10 NEC cases and 6 controls were randomly selected in the neonatal ICU ward of Nanjing maternal and child health care hospital to analyze the 16S rRNA metagenomic diversity of the for intestinal flora. The fecal samples and corresponding environmental samples were corrected from 51 cases of NEC children and their case controls to isolate and culture Clostridium. Results The dispersion of samples within the case group was smaller than that of the control group, and the sample diversity was higher than that of the control group. In the isolation and culture of Clostridium, the overall detection rate of Clostridium in the case group was 43.14% (22/51), and the detection rate of Clostridium butyricum was the highest (19.61%, 10/51). There was a statistical difference between the two groups (χ²=5.85, P=0.015 58). All Clostridium strains did not carry the A, B and E type neurotoxin genes. Conclusion: Increased intestinal flora diversity, intestinal flora abundance and changes in the abundance of Clostridium may be closely related to the intestinal environment of children with NEC; Clostridium, especially Clostridium butyricum, may be related to the occurrence of NEC.