Objective:To investigate the role of umbilical cord mesenchymal stem cell (MSC) -derived nanovesicles in hair regeneration.Methods:(1) Nanovesicles were prepared by continuously extruding umbilical cord MSCs through polycarbonate membranes, and were identified using transmission electron microscopy and nanoparticle tracking analysis. (2) Six C57BL/6 female mice with full-thickness skin wounds were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles once at the wound margin) and a control group (subcutaneously injected with an equal volume of phosphate-buffered saline [PBS] at the wound margin) ; skin samples were collected on day 16 for hematoxylin-eosin (HE) staining to assess wound healing and hair follicle regeneration. (3) Human hair follicle dermal papilla cells (DPCs) were isolated using a two-step enzyme method; the uptake of PKH26-pre-labeled nanovesicles by DPCs was observed by fluorescence microscopy; the proliferative activity of DPCs co-cultured with nanovesicles was evaluated using cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. (4) Six healthy C57BL/6 female mice were randomly divided into two groups after anesthesia, and subcutaneously injected with either fluorescent dye DIR-pre-labeled nanovesicles or PBS; an in vivo imaging system was used to observe the uptake and metabolism of nanovesicles in the mouse skin. (5) Twenty-four C57BL/6 female mice with depilated backs were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles on days 0, 8, and 15) and a control group (subcutaneously injected with an equal volume of PBS at the same time points) ; skin samples were collected on days 4, 18, and 21 for HE staining to analyze differences in hair follicle cycling; transcriptome sequencing was performed on skin samples collected on day 4. Statistical analyses were conducted using the t test. Results:(1) Transmission electron microscopy showed that nanovesicles exhibited a spherical membranous structure with diameters of 141.3 ± 60.0 nm. (2) In 6 C57BL/6 female mice with full-thickness skin wounds, the wound area on day 12 was significantly smaller in the nanovesicle group (1.27 ± 0.50 mm 2) than in the control group (4.13 ± 1.03 mm 2, t = 4.34, P = 0.012). (3) Fluorescence microscopy revealed that nanovesicles were taken up by DPCs within 20 hours; the absorbance of DPCs was significantly higher in the nanovesicle group than in the control group ( t = 20.23, P < 0.001), and the percentage of EdU-positive cells was also significantly higher in the nanovesicle group (49.62% ± 6.45%) than in the control group (37.58% ± 3.42%, t = 3.69, P = 0.006). (4) In vivo imaging of the 6 C57BL/6 female mice showed strong fluorescence in the back of mice in the nanovesicle group on day 0, which markedly decreased by day 8, while no fluorescence was observed in the control group throughout the experiment. (5) Hair follicle cycle experiments on the 24 C57BL/6 female mice with depilated backs showed that the hair follicle length on day 4 after depilation was significantly longer in the nanovesicle group (368.00 ± 63.17 μm) than in the control group (266.90 ± 34.41 μm, t = 9.87, P < 0.001), and the hair bulb diameter was also significantly longer in the nanovesicle group (54.83 ± 10.32 μm) than in the control group (39.12 ± 7.54 μm, t = 16.02, P < 0.001) ; on day 18, the nanovesicle group showed a significantly higher hair follicle density (19.12 ± 0.90) compared with the control group (11.07 ± 1.51, t = 7.92, P = 0.001) ; on day 21, 46.13% ± 8.64% of hair follicles in the nanovesicle group remained in the anagen phase Ⅵ to the catagen phase Ⅱ, and 46.24% ± 3.29% were in the catagen phases Ⅲ to Ⅳ, while 78.89% ± 18.36% of hair follicles in the control group were in the telogen phases Ⅶ to Ⅷ. Transcriptome sequencing showed that differentially expressed genes in the nanovesicle group were significantly positively enriched in the keratinization process (NES = 2.23, P < 0.001) . Conclusion:Umbilical cord MSC-derived nanovesicles could promote the proliferation of DPCs, advance the entry of hair follicles into the anagen phase, delay their entry into the catagen phase, and induce hair regeneration.

Objective To develop and validate a risk prediction model for social dysfunction in middle-aged and elderly patients with ischemic stroke.Methods A non-matched case-control study was conducted among ischemic stroke patients admitted to the neurology department of a tertiary hospital in Tangshan between August 2022 and March 2023.Patients who developed social dysfunction within 3 months after discharge were assigned to a case group,while those without it were assigned to a control group.Multivariate logistic regression was used to identify significant predictors and construct a nomogram-based prediction model.The model's discrimination and calibration were assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Internal validation was performed via bootstrap resampling,and clinical utility was evaluated using decision curve analysis.Results Logistic regression identified the following as significant risk factors for social dysfunction(P＜0.05):male gender,age≥60 years,primary education or below,rural residence,income＜3 000,cognitive impairment,low disability acceptance,poor self-management ability,suboptimal utilization of chronic disease resources,low future-oriented coping,and high cumulative ecological risk.The nomogram achieved an AUC of 0.874,with a sensitivity of 79.4％and specificity of 80.7％.The Hosmer-Lemeshow test indicated good calibration(x2=3.631,P=0.88).Conclusion The developed nomogram provides an effective tool for predicting the risk of social dysfunction in middle-aged and elderly ischemic stroke patients,facilitating early identification of high-risk individuals.

Objective:To investigate the role of umbilical cord mesenchymal stem cell (MSC) -derived nanovesicles in hair regeneration.Methods:(1) Nanovesicles were prepared by continuously extruding umbilical cord MSCs through polycarbonate membranes, and were identified using transmission electron microscopy and nanoparticle tracking analysis. (2) Six C57BL/6 female mice with full-thickness skin wounds were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles once at the wound margin) and a control group (subcutaneously injected with an equal volume of phosphate-buffered saline [PBS] at the wound margin) ; skin samples were collected on day 16 for hematoxylin-eosin (HE) staining to assess wound healing and hair follicle regeneration. (3) Human hair follicle dermal papilla cells (DPCs) were isolated using a two-step enzyme method; the uptake of PKH26-pre-labeled nanovesicles by DPCs was observed by fluorescence microscopy; the proliferative activity of DPCs co-cultured with nanovesicles was evaluated using cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays. (4) Six healthy C57BL/6 female mice were randomly divided into two groups after anesthesia, and subcutaneously injected with either fluorescent dye DIR-pre-labeled nanovesicles or PBS; an in vivo imaging system was used to observe the uptake and metabolism of nanovesicles in the mouse skin. (5) Twenty-four C57BL/6 female mice with depilated backs were randomly divided into a nanovesicle group (subcutaneously injected with nanovesicles on days 0, 8, and 15) and a control group (subcutaneously injected with an equal volume of PBS at the same time points) ; skin samples were collected on days 4, 18, and 21 for HE staining to analyze differences in hair follicle cycling; transcriptome sequencing was performed on skin samples collected on day 4. Statistical analyses were conducted using the t test. Results:(1) Transmission electron microscopy showed that nanovesicles exhibited a spherical membranous structure with diameters of 141.3 ± 60.0 nm. (2) In 6 C57BL/6 female mice with full-thickness skin wounds, the wound area on day 12 was significantly smaller in the nanovesicle group (1.27 ± 0.50 mm 2) than in the control group (4.13 ± 1.03 mm 2, t = 4.34, P = 0.012). (3) Fluorescence microscopy revealed that nanovesicles were taken up by DPCs within 20 hours; the absorbance of DPCs was significantly higher in the nanovesicle group than in the control group ( t = 20.23, P < 0.001), and the percentage of EdU-positive cells was also significantly higher in the nanovesicle group (49.62% ± 6.45%) than in the control group (37.58% ± 3.42%, t = 3.69, P = 0.006). (4) In vivo imaging of the 6 C57BL/6 female mice showed strong fluorescence in the back of mice in the nanovesicle group on day 0, which markedly decreased by day 8, while no fluorescence was observed in the control group throughout the experiment. (5) Hair follicle cycle experiments on the 24 C57BL/6 female mice with depilated backs showed that the hair follicle length on day 4 after depilation was significantly longer in the nanovesicle group (368.00 ± 63.17 μm) than in the control group (266.90 ± 34.41 μm, t = 9.87, P < 0.001), and the hair bulb diameter was also significantly longer in the nanovesicle group (54.83 ± 10.32 μm) than in the control group (39.12 ± 7.54 μm, t = 16.02, P < 0.001) ; on day 18, the nanovesicle group showed a significantly higher hair follicle density (19.12 ± 0.90) compared with the control group (11.07 ± 1.51, t = 7.92, P = 0.001) ; on day 21, 46.13% ± 8.64% of hair follicles in the nanovesicle group remained in the anagen phase Ⅵ to the catagen phase Ⅱ, and 46.24% ± 3.29% were in the catagen phases Ⅲ to Ⅳ, while 78.89% ± 18.36% of hair follicles in the control group were in the telogen phases Ⅶ to Ⅷ. Transcriptome sequencing showed that differentially expressed genes in the nanovesicle group were significantly positively enriched in the keratinization process (NES = 2.23, P < 0.001) . Conclusion:Umbilical cord MSC-derived nanovesicles could promote the proliferation of DPCs, advance the entry of hair follicles into the anagen phase, delay their entry into the catagen phase, and induce hair regeneration.

Objective To develop and validate a risk prediction model for social dysfunction in middle-aged and elderly patients with ischemic stroke.Methods A non-matched case-control study was conducted among ischemic stroke patients admitted to the neurology department of a tertiary hospital in Tangshan between August 2022 and March 2023.Patients who developed social dysfunction within 3 months after discharge were assigned to a case group,while those without it were assigned to a control group.Multivariate logistic regression was used to identify significant predictors and construct a nomogram-based prediction model.The model's discrimination and calibration were assessed using the area under the receiver operating characteristic curve(AUC)and the Hosmer-Lemeshow test.Internal validation was performed via bootstrap resampling,and clinical utility was evaluated using decision curve analysis.Results Logistic regression identified the following as significant risk factors for social dysfunction(P＜0.05):male gender,age≥60 years,primary education or below,rural residence,income＜3 000,cognitive impairment,low disability acceptance,poor self-management ability,suboptimal utilization of chronic disease resources,low future-oriented coping,and high cumulative ecological risk.The nomogram achieved an AUC of 0.874,with a sensitivity of 79.4％and specificity of 80.7％.The Hosmer-Lemeshow test indicated good calibration(x2=3.631,P=0.88).Conclusion The developed nomogram provides an effective tool for predicting the risk of social dysfunction in middle-aged and elderly ischemic stroke patients,facilitating early identification of high-risk individuals.

Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is un-known.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifying β-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs with β-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate that β-glucan-modified MSN,with a particle size of-100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple thera-peutic agents that target other lymph-mediated diseases.

Particle size and surface properties are crucial for lymphatic drainage (LN), dendritic cell (DC) uptake, DC maturation, and antigen cross-presentation induced by nanovaccine injection, which lead to an effective cell-mediated immune response. However, the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles (MSNs) affect this immune response is unknown. We prepared 50, 100, and 200 nm of MSNs that adsorbed ovalbumin antigen (OVA) while modifying β-glucan to enhance immunogenicity. The results revealed that these MSNs with different particle sizes were just as efficient in vitro, and MSNs with β-glucan modification demonstrated higher efficacy. However, the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs. The results also indicate that β-glucan-modified MSN, with a particle size of ∼100 nm, has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.

Objective:The aim of this study is to establish the reference interval of refined immune cell subsets by multi-parameter flow cytometry.Methods:In this cross sectional study, a total of 326 healthy participants were included and divided into two groups based on age: 18-40 years old group and 41-60 years old group. Peripheral venous blood was collected in a fasting status. Flow cytometry tests were performed according to previous consensus article. The analysis of reference interval was conducted according to the documents of Clinical and Laboratory Standards Institute (CLSI) EP28-A3c and Health Industry Standards of the People′s Republic of China WS/T 402-2024.Results:The T,B,NK,DC and monocyte refined immune cell subsets applicable to the reference range of the general population mainly include: CD3 +(56.4%-83.3%),CD4 +TEMRRA (0.2%-11.6%), CD4 +TEM (14.9%-52.8%), CD4 +CD28 +(76.3%-99.9%), CD19 +CD5 +(9.7%-45.8%), CD19 +CD27 -(45.7%-90.0%), CD19 +CD27 +(9.8%-54.0%), CD3 +CD16 +CD56 +(1.3%-20.2%), CD3 -CD19 -CD20 -CD14 -CD56 -HLA-DR +(0.4%-2.0%), Monocyte Mo1 subset CD14 +CD16 -(46.3%-94.6%), monocyte Mo2 subset CD14 +CD16 +(2.8%-49.7%), etc. When the Z-value between different age groups was higher than Z* (3.50 cut-off value), the reference intervals of these subsets should be established independently according to age. Conclusions:In this study, the reference intervals of refined subsets of immune cells by multi-parameter flow cytometry has been preliminarily established. For those subgroups that meet the grouping criteria, age should be fully considered in clinical applications and laboratory validation.

Objective:The aim of this study is to establish the reference interval of refined immune cell subsets by multi-parameter flow cytometry.Methods:In this cross sectional study, a total of 326 healthy participants were included and divided into two groups based on age: 18-40 years old group and 41-60 years old group. Peripheral venous blood was collected in a fasting status. Flow cytometry tests were performed according to previous consensus article. The analysis of reference interval was conducted according to the documents of Clinical and Laboratory Standards Institute (CLSI) EP28-A3c and Health Industry Standards of the People′s Republic of China WS/T 402-2024.Results:The T,B,NK,DC and monocyte refined immune cell subsets applicable to the reference range of the general population mainly include: CD3 +(56.4%-83.3%),CD4 +TEMRRA (0.2%-11.6%), CD4 +TEM (14.9%-52.8%), CD4 +CD28 +(76.3%-99.9%), CD19 +CD5 +(9.7%-45.8%), CD19 +CD27 -(45.7%-90.0%), CD19 +CD27 +(9.8%-54.0%), CD3 +CD16 +CD56 +(1.3%-20.2%), CD3 -CD19 -CD20 -CD14 -CD56 -HLA-DR +(0.4%-2.0%), Monocyte Mo1 subset CD14 +CD16 -(46.3%-94.6%), monocyte Mo2 subset CD14 +CD16 +(2.8%-49.7%), etc. When the Z-value between different age groups was higher than Z* (3.50 cut-off value), the reference intervals of these subsets should be established independently according to age. Conclusions:In this study, the reference intervals of refined subsets of immune cells by multi-parameter flow cytometry has been preliminarily established. For those subgroups that meet the grouping criteria, age should be fully considered in clinical applications and laboratory validation.

Objective To systematically evaluate the optimal dose of early enteral nutrition support in critically ill patients.Methods Systematic search database including PubMed,Web of science,Scopus,CINAHL,CBM,CNKI.RCTs about early enteral nutrition dose selections in critically ill patients were chosen according to include and exclude criteria by two researchers independently.Cochrane system evaluation manual bias risk assessment was used to evaluate quality of literature.RevMan5.3 Meta analysis software was used to analyze the data.Results A total of 1 571 literatures were retrieved and 8 RCT studies were included,2 713 subjects in total.Meta analysis results showed that there were statistically significant differences in mechanical ventilation time,incidence of diarrhea,and utilization rate of gastro dynamic drugs between trophic feeding and full feeding (P＜0.05).There were no statistically significant differences in mortality,length of stay,incidence of nosocomial infections,reflux,vomiting,constipation,etc.(P＞0.05).Conclusions Trophic feeding has familiar effects on mortality,length of hospital stay compared to full feeding,but it can help to shorten ICU mechanical ventilation time,improve the gastrointestinal tolerability.

Based on the conception analysis of the organizational change leadership of the upper-and mid-level nursing manager,this review described connovations of the organizational change leadership and its applications in nursing field at home and abroad,and pointed out the current research status,limitations and the inspirations we got,so as to provide references for promotion and evaluation of the upper-and midlevel nursing manager's organizational change leadership.