BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:Nanocell vesicles possess functions such as re-epithelialization,antioxidation,anti-inflammation,and regulation of extracellular matrix remodeling.Meanwhile,apoptotic bodies have the immunomodulatory effects.Therefore,the combination of the two to form nanofusion vesicles can synergistically promote the healing of diabetic skin wounds.OBJECTIVE:To elucidate the impact of nanofusion vesicles on skin wound healing in a diabetic murine model.METHODS:(1)Material preparation and characterization:The primary bone marrow mesenchymal stem cells of C57BL/6J neonatal mice and the neutrophil apoptotic bodies of C57BL/6J mice were isolated and extracted.The nanofusion vesicles were prepared by micro-extrusion mechanism.(2)In vitro experiment:MTT assay was used to detect the proliferative effect of different concentrations of nanofusion vesicles on NIH-3T3 cells and human umbilical vein endothelial cells.Reactive oxygen species fluorescence probe was used to detect the antioxidant effect of nano-fusion vesicles on NIH-3T3 cells treated with hydrogen peroxide(H2O2).The inhibitory effect of nanofusion vesicles on RAW 264.7 macrophage inflammation induced by lipopolyside was detected by real-time quantitative RT-qPCR.(3)In vivo experiment:36 male C57BL/6J mice were employed to develop a murine model of diabetes mellitus.Following the successful induction of diabetes,two circular full-thickness wounds,each with a diameter of 6 mm,were created on either side of the diabetic mice's spine using a skin punch.The mice were divided into three groups by random number table method.The control group was injected with 0.1 mL of phosphate buffer solution.The nanovesicle group was injected with 0.1 mL nanovesicles(25 μg/mL).The nanofusion vesicle group was injected with 0.1 mL nanofusion(25 μg/mL)vesicles.After treatment for three consecutive days,the wound healing and histomorphological changes were observed.RESULTS AND CONCLUSION:(1)In vitro experiment:nanofusion vesicles,when administered at concentrations ranging from 0 to 100 μg/mL,exhibited no toxic effects and promoted the proliferation of NIH-3T3 and HUVEC cell lines.Notably,a concentration of 25 μg/mL nanofusion vesicle significantly enhanced the proliferation of NIH-3T3 cells.Furthermore,the survival rate of human umbilical vein endothelial cells was observed to increase in correlation with escalating concentrations of nanofusion vesicles.Nanofusion vesicles had a good antioxidant effect.In comparison to the H2O2 group,the fluorescence signal indicative of reactive oxygen species was progressively diminished in both the nanovesicle group and the nanofusion vesicle group.Furthermore,nanofusion vesicles possessed anti-inflammatory capabilities,effectively mitigating the inflammatory response in macrophages triggered by lipopolysaccharide stimulation.(2)In vivo experiment:Hematoxylin-eosin and Masson's trichrome staining revealed that in comparison to the control group,both the nanovesicle group and the nanofusion vesicle group exhibited a significant increase in granulation tissue formation and collagen fiber deposition within the wounds by day 6.Notably,the nanofusion vesicle group displayed the most pronounced effects.On day 12,the wound of nanofusion vesicle group was significantly reduced,and the healing rate was significantly faster than that of other groups(P＜0.01),and the effect of promoting wound healing was the most significant.Our findings demonstrated that nanofusion vesicles exhibited superior pro-cell proliferative,antioxidant,and anti-inflammatory properties,thereby exerting a beneficial effect on the promotion of skin wound healing in diabetic mouse models.

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

BACKGROUND:MXene nanoparticles,due to their unique hydrophilicity,biocompatibility,and antibacterial properties,are widely used in wound,tumor,nerve repair,and cardiovascular treatments.However,it is still unclear what effect MXene nanoparticles have on diabetic wound healing.OBJECTIVE:To investigate the in vitro antioxidant,anti-inflammatory and photothermal antibacterial properties of MXene nanoparticles Ti3C2Tx as well as their effect on wound repair in diabetic mice.METHODS:(1)In vitro experiments:The cytotoxicity of Ti3C2Tx nanoparticles on mouse fibroblasts(NIH-3T3)at various concentrations was evaluated using the methyl thiazolyl tetrazolium(MTT)assay.NIH-3T3 cells were exposed to H2O2,and the MTT assay was used to detect the protective effects of different mass concentrations of Ti3C2Tx on NIH-3T3 cells.NIH-3T3 cells were exposed to H2O2,and the effect of Ti3C2Tx(20 μg/mL)on the generation of reactive oxygen species in NIH-3T3 cells was analyzed under illumination(or no illumination)treatment.RAW264.7 macrophages were divided into three groups:control group,lipopolysaccharide group,and lipopolysaccharide+Ti3C2Tx group.Real-time quantitative PCR was used to detect the expression of specific genes(CD86,interleukin 6,CD206,arginase 1)in the cells.Escherichia coli(or Staphylococcus aureus)were divided into three groups:control group,Ti3C2Tx group,and Ti3C2Tx illumination group.The bacterial survival rate was calculated by plate colony counting method.(2)In vivo experiments:Streptozotocin was administered intraperitoneally to ICR mice to induce a diabetic condition.After successful modeling,a full-thickness skin defect wound was created on the back of the mice using a circular punch.The experiment was divided into three groups:control group(n=6),Ti3C2Tx group(n=6),and Ti3C2Tx illumination group(n=6).The wound healing was observed,and CD31 and CD206 immunohistochemical staining of wound tissue was performed on day 7 after intervention.Hematoxylin-eosin staining and Masson staining of wound tissue were performed on days 7 and 14 after intervention.Ti3C2Tx solution was injected subcutaneously into ICR mice.After illumination(or non-illumination)exposure,the toxic effects of Ti3C2Tx on mice were analyzed by blood biochemical detection.RESULTS AND CONCLUSION:(1)In vitro experiments:Ti3C2Tx showed no cytotoxicity on NIH-3T3 cells at mass concentrations ranging from 5-160 μg/mL.It increased the survival rate of NIH-3T3 cells at a mass concentration of 20 μg/mL.Ti3C2Tx at 10-80 μg/mL significantly improved the survival rate of NIH-3T3 cells under H2O2 intervention.Ti3C2Tx significantly inhibited the generation of reactive oxygen species in NIH-3T3 cells under the intervention of H2O2,and illumination treatment further enhanced the effect of Ti3C2Tx on inhibiting the generation of reactive oxygen species.Ti3C2Tx effectively inhibited macrophage inflammation induced by lipopolysaccharide and promoted the transformation of cells into M2 macrophages with anti-inflammatory properties.Both Ti3C2Tx and Ti3C2Tx illumination significantly inhibited the growth of Escherichia coli and Staphylococcus aureus,and the inhibitory effect of Ti3C2Tx illumination was more significant.(2)In vivo experiments:Gross and histological analyses of the wound surface showed that both Ti3C2Tx and Ti3C2Tx illumination promoted wound healing in diabetic mice,and the promotion effect of Ti3C2Tx irradiation was more significant.Immunohistochemical staining results showed that both Ti3C2Tx and Ti3C2Tx illumination inhibited the inflammatory response in diabetic wounds and promoted angiogenesis,and the effect of Ti3C2Tx illumination was more significant.Blood biochemical test results showed that Ti3C2Tx and illumination had no obvious toxic effects on mice.(3)These results indicate that Ti3C2Tx nanoparticles efficiently promote the healing of skin wounds in a diabetic mouse model through antioxidation,anti-inflammation,and antibacterial actions via photothermal effects.

BACKGROUND:Confirming the reliability and validity of the My jump 2 application for measuring lower limb vertical stiffness may offer the possibility of it as an alternative to the Kistler three-dimensional force platform for measuring lower limb stiffness. OBJECTIVE:To verify the reliability and validity of the My Jump 2 application in measuring lower limb vertical stiffness of college students. METHODS:The drop jump data of the participants were collected through the Kistler three-dimensional force platform and the My Jump 2 application,and the vertical stiffness of the participants'lower limb vertical stiffness was calculated.The intraclass correlation coefficient was used to analyze the data measured by the My Jump 2 application and the Kistler three-dimensional force platform,attempting to verify the reliability of the My Jump 2 application.The bias and average between the two devices were drawn into a Bland-Altman diagram to verify the consistency between the two test methods.Finally,the test-retest reliability of the My Jump 2 applications at 30 cm and 40 cm was analyzed using the Cronbach's alpha(α)and coefficient of variation.Pearson product-moment correlation was used to analyze the correlation of My Jump 2 applications. RESULTS AND CONCLUSION:My Jump 2 application has high reliability and validity when measuring the vertical stiffness of the lower limb.At the same time,due to its advantages of low cost,convenient portability and field testing for large samples,it can be used as an alternative to the Kistler three-dimensional force platform to test the vertical stiffness of the lower limb in college students and similar populations.

Objective:To evaluate the medium-term clinical and hemodynamic outcomes of percutaneous pulmonary valve implantation (PPVI) using a domestic Venus-P self-expanding valve in the treatment of severe pulmonary regurgitation after Tetralogy of Fallot (TOF).Methods:Retrospective study.From December 2017 to December 2020, 13 TOF patients with (17.8±4.7) years old and (50.2±12.3) kg underwent PPVI using the Venus-P self-expanding valve in the Department of Children′s Heart Center, Zhengzhou University People′s Hospital were recruited.The mean valve size was (31.9±3.1) mm.All patients received the transannular patch surgery and developed severe pulmonary regurgitation.After PPVI, 13 patients were followed up for at least 12 months.The operation-related complications, improvement of valve and heart function and the durability and reintervention of the Venus-P self-expanding valve were analyzed.The right ventricular end-diastolic volume index (RVEDVi) before and after operation was compared by the paired t-test, and the New York Heart Association (NYHA) class was compared by the paired Wilcoxon signed rank sum test. Results:PPVI was successfully performed in all 13 patients without death.At 6 months post-PPVI, cardiac magnetic resonance imaging findings showed that RVEDVi was significantly reduced[(145.7±9.6) mL/m 2vs.(100.2±12.2) mL/m 2, P<0.05], and the NYHA class was significantly improved ( P<0.05). One patient presented moderate pulmonary valve regurgitation at 12 months postoperatively.No vegetation was found on echocardiography, and blood culture was negative in this case.Six patients did not have postoperative pulmonary valve regurgitation, and the remaining presented mild or less pulmonary regurgitation.One patient had sudden ventricular tachycardia on the 6 th day postoperatively, which was converted to sinus rhythm after synchronous electrocardiography.Only one case underwent appendectomy 7 months after operation due to acute appendicitis, and the remaining did not require valve-related reintervention after implantation.During the follow-up for (22.8±8.0) months, no patients had perivalve leakage, stent migration and rupture.Complications like embolization and coronary artery compression were not reported. Conclusions:PPVI using the Venus-P self-expanding valve is safe and effective in patients with severe pulmonary valve regurgitation after TOF surgery, showing an acceptable medium-term follow-up outcome.Studies with a large sample size and long follow-up period are still needed to validate our findings.

Background: Chronic functional constipation is a common functional gastrointestinal disorder, and the effects of traditional therapeutic drugs are suboptimal. Prucalopride is a novel 5-HT

Estrogen receptor (esr) mediates the effects of estrogen on the expression of related genes, thereby regulating the growth and reproduction of mammals. To investigate the effect of retrotransposon insertion polymorphism (RIP) of the porcine esr gene on porcine growth performance, retrotransposon insertion polymorphism of the esr gene were predicted by comparative genomics and bioinformatics, and PCR was used to verify the insertion polymorphisms in different porcine breeds. Finally, the correlation analysis between the genotypes and performance of Large White pigs was conducted. The results showed that four retrotransposon polymorphic sites were identified in the esr1 and esr2 genes, which are esr1-SINE- RIP1 located in intron 2 of the esr1 gene, esr1-LINE-RIP2 and RIP3-esr1- SINE located in intron 5 of the gene, and esr2-LINE-RIP located in intron 1 of the esr2 gene, respectively. Among them, insertion of a 287 bp of SINE into intron 2 of the esr1 gene significantly affected (P<0.05) the live back fat thickness and 100 kg body weight back fat thickness of Large White pigs. Moreover, the live back fat thickness and back fat thickness at 100 kg body weight of homozygous with insertion (SINE+/+) was significantly greater than that of heterozygous with insertion (SINE+/-) and homozygous without insertion (SINE-/-). Therefore, esr1-SINE-RIP1 could be used as a molecular marker to assist the selection of deposition traits in Large White pigs.
Animals ; Genotype ; Introns/genetics* ; Phenotype ; Polymorphism, Genetic/genetics* ; Retroelements/genetics* ; Swine/genetics*

Objective: To analyze the treatment effect of patients with glioblastoma (GBM) and explore prognostic factors. Methods: The clinical data of 635 patients diagnosed as GBM at Neurosurgical Oncology Department Ⅳ of Beijing Tiantan Hospital, Capital Medical University from January 2007 to March 2018 were retrospectively reviewed. There were 386 males and 249 females with an age of (48.7±11.8) years (range: 18-75 years). Patients were divided into three groups according to the time of admission: 2007-2010 group(n=174), 2011-2014 group (n=237) and 2015-2018 group (n=224). Kaplan-Meier plot was used to analyze the effects of different treatment periods, treatment schemes and clinical factors on the survival of patients with GBM. Cox proportion hazard regression analysis was used to identify independent prognostic factors. Results: The median progression-free survival (PFS) and overall survival (OS) of patients in 2007-2010 group, 2011-2014 group, 2015-2018 group was 9.0 months (95% CI: 7.5-10.5), 10.0 months (95% CI: 8.8-11.2), 12.0 months (95% CI: 10.7-13.3) and 17.0 months (95% CI: 13.2-20.8), 20.0 months (95% CI: 16.9-23.1), 23.0 months(95% CI: 17.5-28.5), respectively. The PFS and OS of patients improved significantly over the years (χ²=9.693, P=0.008 and χ²=8.616, P=0.013). Multivariate survival analysis showed that age, extent of resection, radiotherapy and tumor distant dissemination were independent prognostic factors (all P<0.05). Conclusions With the continuous development of clinical treatment regimen, the therapeutic effect of Chinese GBM patients has improved remarkably. Age, extent of resection, radiotherapy and tumor distant dissemination are independent prognostic factors associated with survival time.