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.

Objective:To investigate the effects of exergaming on the cognitive functions and negative symp-toms in patients with schizophrenia.Methods:Sixty hospitalized patients meeting ICD-10 diagnostic criteria for schizophrenia were randomly assigned to the exergaming group(n=30)and the conventional treatment group(n=30).The exergaming group received structured exergaming therapy in addition to conventional treatment.Cognitive function was assessed with the MATRICS Consensus Cognitive Battery(MCCB)and Mini-Mental State Examina-tion(MMSE),while positive and negative symptoms were evaluated with the Scale for the Assessment of Positive Symptoms(SAPS)and Scale for the Assessment of Negative Symptoms(SANS).Results:Both groups showed significant improvements in the MCCB scores(Trail Making Test,Symbol Coding,Animal Naming,Maze,and Learning Tests)and MMSE scores post-intervention(time main effect,group main effect,and time × group inter-action,Ps＜0.05).The exergaming group showed significantly greater improvements in most cognitive domains compared to the control group.The SANS scores decreased significantly in both groups,with a greater reduction in the exergaming group(P＜0.05).The SAPS scores also declined,but no significant between-group differences were observed(P＞0.05).Conclusion:Exergaming could effectively improve the cognitive deficits and negative symptoms in patients with schizophrenia.

Objective:To investigate the effects of exergaming on the cognitive functions and negative symp-toms in patients with schizophrenia.Methods:Sixty hospitalized patients meeting ICD-10 diagnostic criteria for schizophrenia were randomly assigned to the exergaming group(n=30)and the conventional treatment group(n=30).The exergaming group received structured exergaming therapy in addition to conventional treatment.Cognitive function was assessed with the MATRICS Consensus Cognitive Battery(MCCB)and Mini-Mental State Examina-tion(MMSE),while positive and negative symptoms were evaluated with the Scale for the Assessment of Positive Symptoms(SAPS)and Scale for the Assessment of Negative Symptoms(SANS).Results:Both groups showed significant improvements in the MCCB scores(Trail Making Test,Symbol Coding,Animal Naming,Maze,and Learning Tests)and MMSE scores post-intervention(time main effect,group main effect,and time × group inter-action,Ps＜0.05).The exergaming group showed significantly greater improvements in most cognitive domains compared to the control group.The SANS scores decreased significantly in both groups,with a greater reduction in the exergaming group(P＜0.05).The SAPS scores also declined,but no significant between-group differences were observed(P＞0.05).Conclusion:Exergaming could effectively improve the cognitive deficits and negative symptoms in patients with schizophrenia.

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.

Purpose/Significance Disease description texts are analyzed to reach a deeper understanding of the current status of on-line consultations for sleep disorders and the thematic characteristics of users with sleep disorders.Method/Process Data about sleep dis-orders from"haodf.com"website is collected by using a web crawler.Furthermore,the main themes about patients'description are i-dentified by the latent Dirichlet allocation(LDA)model.Result/Conclusion The departments of sleep disorders are more dispersed,and the main treatment is drug therapy.Online consultations could improve 83.2％of patients'condition.The themes of patients's disease descriptions include medication and consultation,external environment,description of symptoms,surrogate questions and causes.It is suggested that the platform and doctors should pay attention to the prognosis of patients'medication and mental health status,and pay at-tention to the popularization of comorbidities.

Objective To construct oligomeric hyaluronic acid(5 KDa)-modified ellagic acid-loaded liposomes(EA-HA-L)to improve the aqueous solubility,in vitro transdermal effect and whitening activity of ellagic acid.Methods Oligomeric hyaluronic acid-modified cholesterol(HA-Chol)was prepared by esterification reaction and structurally characterized by FTIR and 1H NMR;Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes were prepared by film dispersion-ultrasound method,and the prescribing process was optimized by Box-Behnken design-response surface method,and the particle sizes,the polydispersity index(PDI),zeta potential and encapsulation rate of liposomes under the optimal prescribing process were determined;the difference in solubility between EA-HA-L and free EA was evaluated;in vitro transdermal effect of liposomes were investigated using rat abdominal skin;inhibitory effect on tyrosinase and intracellular tyrosinase in mouse melanoma cells(B16-F10)was surveyed via dopa oxidation method.Results HA-Chol was synthesized and characterized;the optimized prescription process was mass ratio of 10:1 for soy phospholipids to HA-Chol,lipid-drug ratio of 40:1,hydration temperature of 30℃,hydration time of 60 min,ultrasound intensity of 35％,ultrasound time of 21 min,and the particle size of EA-HA-L produced under the optimized prescription process was(140.30±1.30)nm,PDI was(0.29±0.01),the encapsulation rate of ellagic acid was 91.16％±3.06％,and the zeta potential was(-5.67±0.09)mV;after EA was encapsulated by liposomes,the solubility of EA in water increased by about 40-fold;the cumulative transdermal amount of EA-HA-L was 46.98±2.17 μg·cm-2 in 24 h,and the intradermal retention was 66.15±0.61 μg·cm-2,which was 1.72 times higher than that of free EA(P<0.0001)and 1.23 times higher than plain liposome(EA-L)(P<0.01);and the tyrosinase inhibitory activity of EA-HA-L was higher than that of both free EA and EA-L in the EA concentration range of 50-400 μg·mL-1.Conclusion Oligomeric hyaluronic acid-modified ellagic acid-loaded liposomes with small particle size and high encapsulation rate were successfully prepared.EA-HA-L significantly improved the water solubility of EA and possessed better transdermal effect and stronger whitening activity than free EA and EA-L.

Objective: To illuminate the epidemic characteristics of Yersiniosis among children in the central city of Beijing and the accuracy of current clinical diagnosis towards Yersiniosis. Methods: Etiological surveillance of diarrheal patients, a total of 3 493 cases, was performed in a children hospital in central area of Beijing from 2011 to 2018 continuously. Collected the epidemiological and clinical information of the cases, analyzed the clinical and etiological diagnosis for Yersiniosis and bacterial dysentery and compared the distribution of Yersiniosis cases with the different symptoms. Results: A total of 3 493 acute diarrhea cases distributed from the age of 6 months to 13 years old, M (P₂₅, P₇₅) was 1.50 (0.75, 3.17) years old. The 28 cases were isolated Yersinia enterocolitica (isolation rate of 0.80%) and they could be diagnosed as Yersiniosis by etiology. The isolation peaked in May and February. A total of 85.71% (24/28) of Yersiniosis cases were under 5-year old. The children of 3-4 age group had the highest isolation rate (1.52%) while the rate (0.18%) of 0-1 age group was the lowest (P=0.025). The Yersinia enteroclitica isolation rates of diarrheal patients with the symptoms including mucus feces, fever, white blood cell (WBC) and red blood cell (RBC) in feces were higher than the patients without these symptoms (P>0.05). The 9 of 28 Yersiniosis cases by etiology diagnosis were clinical diagnosed as bacillary dysentery. Conclusion The infants and young children under 5-year old were the main population of Yersiniosis adolescent patients under 14-year old. The typical symptoms characterized with mucus stool, fever, WBC and RBC by routine microscopic examination. The preliminary clinical diagnosis of Yersiniosis is easily confused with bacterial dysentery.

Objective To illuminate the epidemic characteristics of Yersiniosis among children in the central city of Beijing and the accuracy of current clinical diagnosis towards Yersiniosis. Methods Etiological surveillance of diarrheal patients, a total of 3 493 cases, was performed in a children hospital in central area of Beijing from 2011 to 2018 continuously. Collected the epidemiological and clinical information of the cases, analyzed the clinical and etiological diagnosis for Yersiniosis and bacterial dysentery and compared the distribution of Yersiniosis cases with the different symptoms. Results A total of 3 493 acute diarrhea cases distributed from the age of 6 months to 13 years old, M (P25, P75) was 1.50 (0.75, 3.17) years old. The 28 cases were isolated Yersinia enterocolitica (isolation rate of 0.80%) and they could be diagnosed as Yersiniosis by etiology. The isolation peaked in May and February. A total of 85.71% (24/28) of Yersiniosis cases were under 5?year old. The children of 3-4 age group had the highest isolation rate (1.52%) while the rate (0.18%) of 0-1 age group was the lowest (P=0.025). The Yersinia enteroclitica isolation rates of diarrheal patients with the symptoms including mucus feces, fever, white blood cell (WBC) and red blood cell (RBC) in feces were higher than the patients without these symptoms (P＞0.05). The 9 of 28 Yersiniosis cases by etiology diagnosis were clinical diagnosed as bacillary dysentery. Conclusion The infants and young children under 5?year old were the main population of Yersiniosis adolescent patients under 14?year old. The typical symptoms characterized with mucus stool, fever, WBC and RBC by routine microscopic examination. The preliminary clinical diagnosis of Yersiniosis is easily confused with bacterial dysentery.