To develop a novel polyamino acid-based nanohydrogel drug delivery system for dexamethasone to enhance its delivery efficiency to the inner ear.

Objective A high sodium(HS)diet is believed to affect bone metabolism processes.Clarifying its impact on osseointegration of titanium(Ti)implants holds significant implications for postoperative dietary management of implanted patients. Methods This investigation probed the impact of sodium ions(Na+)on neovascularization and osteogenesis around Ti implants in vivo,utilizing micro-computed tomography,hematoxylin and eosin staining,and immunohistochemical analyses.Concurrently,in vitro experiments assessed the effects of varied Na+concentrations and exposure durations on human umbilical vein endothelial cells(HUVECs)and MC3T3-E1 cells. Results In vivo,increased dietary sodium(0.8%-6.0%)led to a substantial decline in CD34 positive HUVECs and new bone formation around Ti implants,alongside an increase in inflammatory cells.In vitro,an increase in Na+concentration(140-150 mmol/L)adversely affected the proliferation,angiogenesis,and migration of HUVECs,especially with prolonged exposure.While MC3T3-E1 cells initially exhibited less susceptibility to high Na+concentrations compared to HUVECs during short-term exposure,prolonged exposure to a HS environment progressively diminished their proliferation,differentiation,and osteogenic capabilities. Conclusion These findings suggest that HS diet had a negative effect on the early osseointegration of Ti implants by interfering with the process of postoperative vascularized bone regeneration.

Objective To investigate the effect of silk fibroin hydrogel loaded with developmental endothelial locus-1(Del-1)nanoparticles on the healing of chronic skin wounds in mice.Methods The back skin of BALB/c mice(6-8 weeks old)was pressed with a magnet for 12 h and then relaxed for 12 h,for 4 consecutive days to establish a chronic pressure ulcer wound.After infliction,the mice were randomly divided into 3 groups(n=8),and the skin wounds were treated with PBS,silk fibroin hydrogel or Del-1 nanoparticles/silk fibroin hydrogel.The wound healing was recorded with camera to calculate the wound healing rate.In 9 d after treatment,HE and Masson staining were used to observe the wound healing,and immunofluorescence staining for CD 14 and TNF-α was used to compare the appearance frequency of skin macrophages and the expression of inflammatory factors.After Tert-butyl peroxide(TBHP)was used to stimulate mouse macrophage RAW 264.7 cells and mouse vascular endothelial C166 cells,C166 cells were transfected with lentival vector to overexpress Del-1.Crystal violet staining was used to observe the migration of macrophages.RT-qPCR was used to detect the expression of inflammatory factor IL-6.Results The wound healing was significantly faster in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).The expression levels of TNF-α and CD14 in the wound surface were lower(P＜0.01),but collagen deposition and tissue repair were better in the Del-1 nanoparticles/silk fibroin hydrogel group than the silk fibroin hydrogel group and the PBS group(P＜0.01).In vitro experiments,macrophages migrated to endothelial cells stimulated by TBHP,but the migration rate of macrophages was significantly lower in the Del-1 overexpression group(P＜0.01).RT-qPCR confirmed that Del-1 inhibited the transcription of IL-6(P＜0.01).Conclusion Del-1 nanoparticles/silk fibroin hydrogel can significantly accelerate the healing of skin wounds,and its mechanism may be through promoting the regression of inflammation and tissue repair.

Objective:To evaluate effect of diammonium glycyrrhizinate(DG)on lipopolysaccharide(LPS)-induced TLR4/NF-κB inflammatory signaling pathway in BV2 microglial cells and to explore its potential regulatory mechanisms on ameliorating neu-roinflammation.Methods:BV2 microglia injury model was induced by LPS and treated with 20 and 60 μmol/L DG.MTS was used to determine vitality of cells.NO level secreted by cells was detected by Griess.Inflammatory factors TNF-α,IL-6,and IL-1β levels in cell supernatant were measured by ELISA.TNF-α,IL-6,IL-1β,TLR4 and MyD88 mRNA levels were detected by RT-qPCR.Western blot was used to determine expressions of TLR4,MyD88,NF-κB,p-NF-κB,IκB-α and p-IκB-α proteins of cells.Results:Compared with control group,LPS-treated BV2 microglia had significantly lower viability(P<0.05),significantly higher NO secretion(P<0.05),significantly up-regulation levels of inflammatory factors TNF-α,IL-6 and IL-1β(P<0.05),and significantly higher mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),TLR4,MyD88,NF-κB,p-NF-κB,IκB-α,and p-IκB-α protein expressions were significantly increased(P<0.05).Compared with LPS group,BV2 microglia intervened with different concentrations of DG had significantly higher viability(P<0.05),significantly lower NO secretion(P<0.05),significantly lower TNF-α,IL-6 and IL-1β inflammatory factors levels(P<0.05),significantly lower mRNA levels of TNF-α,IL-6,IL-1β,TLR4 and MyD88(P<0.05),and TLR4,MyD88,p-NF-κB and p-IκB-α protein expressions were significantly reduced(P<0.05).Conclusion:DG can inhibit LPS-induced neuroinflammatory responses in microglia,whose underlying mechanism is suppression of TLR4/NF-κB signaling pathway.

Objective:To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization.Methods:The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed.Results:(1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm 3 and cone size <2 cm 3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference ( P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm ( RR=3.084, 95% CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm 3 and those with cone size ≥2 cm 3 ( RR=1.700, 95% CI: 0.935-3.092; P=0.077). Conclusion:The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

Objective:To investigate the efficacy of the intelligent version of the Montreal Cognitive Assessment Scale(MoCA)in identifying mild cognitive impairment(MCI)in elderly inpatients.Methods:Seventy-five patients diagnosed with mild cognitive impairment(MCI group)from the Neurology and Geriatrics Departments of a tertiary hospital in Changsha City, along with 195 patients with normal cognitive function(normal control group), were selected between July 2020 and December 2022.Both groups underwent evaluations using the intelligent version of the Montreal Cognitive Assessment(MoCA)and the Mini Mental State Examination(MMSE), and the results were analyzed.Results:The MCI group showed significantly lower total MoCA scores and MMSE scores[(19.73±2.42) vs.(24.8±2.33)]compared to the normal control group[(24.47±2.02) vs.(26.50±1.65)], with a statistically significant difference( P<0.01).The optimal cut-off score for the MoCA was found to be 23.5 points in diagnosing MCI, showing higher sensitivity, specificity, and kappa value(96.0%, 82.1%, and 0.690)compared to the MMSE scale(90.0%, 62.6%, and 0.428). Conclusions:The intelligent MoCA has a high screening accuracy for identifying MCI in this population, demonstrating superior sensitivity and specificity compared to the MMSE.

OBJECTIVES: Acute ischemic stroke (AIS) is one of the main causes of disability in middle-aged and elderly people, and early activity plays an important role in functional recovery. This study aims to understand the factors that affect the implementation of early activity in patients with AIS and to provide reference for promoting early activity implementation and developing intervention strategies for AIS patients. METHODS: Using purposive sampling, 19 AIS patients and their caregivers who visited at Stroke Center in the Third Xiangya Hospital of Central South University and the Third Hospital of Changsha from June to December 2021, as well as 19 medical staff, hospital administrators, or community workers providing medical health services to stroke patients, were selected as interviewes. A semi-structured interview was conducted based on the social ecological theory model, and the Colaizzi seven-step method was used to analyze the interview data. RESULTS: According to qualitative interview results, the factors affecting early activity in AIS patients were summarized into 4 themes and 12 sub-themes: medical staff factors (insufficient knowledge and skills, insufficient knowledge of early activity, unclear division of responsibilities), patient factors (severity of the disease, lack of knowledge, psychological pressure, fear of falling), social environmental factors (lack of social support, shortage of human resources and rehabilitation equipment, insufficient medical insurance support), and evidence and norms (the evidence for early activity needs improvement, lack of standardized early activity procedures). CONCLUSIONS Early activity in AIS patients is impacted by factors at multiple levels, including medical staff, patients, social environment, and evidence and norms. Developing comprehensive intervention strategies to address these factors can promote early activity implementation in AIS patients.
Aged ; Middle Aged ; Humans ; Ischemic Stroke ; Accidental Falls ; Fear ; Social Environment ; Stroke

Objective:To evaluate the effectiveness of hands-on training and video demonstration in training of forceps delivery for residents.Methods:Forty nine residents who were rotating in the obstetrics department of Peking Union Medical College Hospital from 2019 to 2021 were enrolled. The residents were randomly divided into two groups: the instructor group ( n=24) was taught by hands-on training of forceps delivery and the video group ( n=25) was instructed by watching video demonstration. All the trainees completed the self-confidence questionnaire survey, and were evaluated by written tests and objective structured assessment of technical skills scoring system. Results:The scores of self-confidence in each item after the simulation training were higher than those before training in both groups; and there were no significant differences between two groups in the increment of scores(mastering knowledge: 1.54±0.98 vs. 1.40±0.71, U=266.68, P=0.480;mastering operation skills: 1.42±0.93 vs.1.80±0.87, U=233.47, P=0.161; mastering forceps structure: 1.63±1.10 vs. 1.88±0.93, U=261.63, P=0.416; confidence in independent operation: 1.13±0.90 vs. 1.00±1.08, U=287.74, P=0.799; evaluation of simulation training: 0.21±0.51 vs. 0.16±0.55, U=288.27, P=0.776). In the written tests, the scores of the instructor group were significantly higher than those of the video group (83.00±7.18 vs.70.56±10.37; t=4.86, P<0.001). In the practical operation, the instructor group significantly outperformed the video group in items of “right blade placement” (0.71±0.46 vs. 0.20±0.41, U=147.54, P<0.001), “objective total score” (6.17±1.46 vs. 4.72±1.65, U=155.49, P=0.003) and “correct traction” (0.85±0.31 vs. 0.56±0.51, U=213.86, P=0.036). Conclusion:Training delivered via hands-on instruction and demonstration was generally more effective than that delivered via video, although both groups show a increased self-confidence in learning and performing forceps delivery.

In growing children, growth plate cartilage has limited self-repair ability upon fracture injury always leading to limb growth arrest. Interestingly, one type of fracture injuries within the growth plate achieve amazing self-healing, however, the mechanism is unclear. Using this type of fracture mouse model, we discovered the activation of Hedgehog (Hh) signaling in the injured growth plate, which could activate chondrocytes in growth plate and promote cartilage repair. Primary cilia are the central transduction mediator of Hh signaling. Notably, ciliary Hh-Smo-Gli signaling pathways were enriched in the growth plate during development. Moreover, chondrocytes in resting and proliferating zone were dynamically ciliated during growth plate repair. Furthermore, conditional deletion of the ciliary core gene Ift140 in cartilage disrupted cilia-mediated Hh signaling in growth plate. More importantly, activating ciliary Hh signaling by Smoothened agonist (SAG) significantly accelerated growth plate repair after injury. In sum, primary cilia mediate Hh signaling induced the activation of stem/progenitor chondrocytes and growth plate repair after fracture injury.
Mice ; Animals ; Hedgehog Proteins/genetics* ; Receptors, G-Protein-Coupled/metabolism* ; Cilia/metabolism* ; Cartilage/metabolism* ; Regeneration

As an important part of tumor microenvironment, neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis. Here we defined, at single-cell resolution, CD44-CXCR2- neutrophils as tumor-specific neutrophils (tsNeus) in both mouse and human gastric cancer (GC). We uncovered a Hippo regulon in neutrophils with unique YAP signature genes (e.g., ICAM1, CD14, EGR1) distinct from those identified in epithelial and/or cancer cells. Importantly, knockout of YAP/TAZ in neutrophils impaired their differentiation into CD54+ tsNeus and reduced their antitumor activity, leading to accelerated GC progression. Moreover, the relative amounts of CD54+ tsNeus were found to be negatively associated with GC progression and positively associated with patient survival. Interestingly, GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+ tsNeus. Furthermore, pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC, with no significant inflammation-related side effects. Thus, our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus, opening a new possibility to develop neutrophil-based antitumor therapeutics.
Humans ; Animals ; Mice ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Stomach Neoplasms/pathology* ; Neutrophils/pathology* ; Signal Transduction/genetics* ; YAP-Signaling Proteins ; Tumor Microenvironment ; Hyaluronan Receptors/genetics*