Objective This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting,clarifies and explores the quality control and supervision model for bioprinting medical devices,and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices.Methods The quality control risk points throughout the bioprinting process were comprehensively analyzed,with a particular focus on bioprinting materials and key processes.The regulatory model and methods for bioprinting medical devices were examined.This research concentrated on critical technologies such as extrusion,laser-assisted,and in situ bioprinting,assessing their potential for clinical applications and regulatory challenges.Results Bioink from different sources should meet regulatory requirements.It is essential to ensure aseptic handling of raw materials and to validate sterilization under"worst-case"conditions.Conclusion As bioprinting technology advances rapidly,corresponding research into materials,processes,and quality risk control should be conducted to ensure the concurrent development of the regulatory system.This will continuously contribute to the orderly progression of the entire industry and human health.

ObjectiveTo investigate the status of self-efficacy, quality of care and quality of life of people with physical disabilities, and analyze the relationship among them. MethodsFrom January, 2019 to December, 2020, 357 people with physical disabilities in Shandong were selected with cluster stratified random sampling, and all the participants were investigated with a general questionnaire, World Health Organization Quality of Life-Disability Scales, General Self-Efficacy Scale and World Health Organization Quality of Care and Support Scale-Disability Scale on internet. ResultsA total of 357 questionnaires were collected, in which 350 were valid. The total score was (115.00±20.70) for quality of life, (23.33±5.78) for self-efficacy, and (50.43±10.56) for quality of care. The quality of life and its each domain was positively correlated with self-efficacy (r > 0.282, P < 0.01), quality of care, care information acquisition, care giving and care environment (r > 0.369, P < 0.01). Employment, self-efficacy and quality of care associated with the quality of life (t > 4.386, P < 0.001); employment, self-efficacy, care giving and care environment associated with the physiological, psychological and environment domains of the quality of life (t > 2.926, P < 0.01); parents as main caregivers, employment, self-efficacy, care giving and care environment associated with social relationships domain of the quality of life (|t| > 2.525, P < 0.05); parents as main caregivers, employment, care giving and care environment associated with the disability domain of the quality of life (|t| > 2.209, P < 0.05). ConclusionThe quality of life needs to be improved for the people with physical disabilities. Self-efficacy and quality of care may impact the quality of life; and it is needed to focus on the people with physical disabilities who are unemployed and whose parents are the main caregivers.

Objective:To investigate the predictive value of pan-immune-inflammation value (PIV) for in-hospital mortality in patients with acute ischemic stroke (AIS) admitted to intensive care unit (ICU).Methods:The clinical data of the first-ever AIS patients admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC) -Ⅳ of the United States were retrospectively included and analyzed. According to whether the patients died in the hospital, they were divided into a survival group and a death group, and the differences in baseline data between the two groups were compared. Multivariate logistic regression model was used to analyze independent influencing factors of in-hospital mortality in patients. Receiver operating characteristic curve was used to evaluate the predictive value of PIV on in-hospital mortality. Results:A total of 1 068 first-ever AIS patients admitted to the ICU were included, with a median age of 69 years. There were 543 males (50.84%), and 182 (17.05%) experienced in-hospital mortality. Multivariate logistic regression analysis showed that after adjusting for potential confounding factors, a higher PIV (>1 555.71) was an independent risk factor for in-hospital mortality in patients (odds ratio 1.924, 95% confidence interval 1.093-3.387; P=0.023). The receiver operating characteristic curve analysis showed that the area under the curve for predicting in-hospital mortality by PIV was 0.605 (95% confidence interval 0.556-0.654), with an optimal cutoff value of 1 199.93. The sensitivity and specificity for predicting in-hospital mortality were 48.9% and 70.2%, respectively. Conclusions:A higher PIV is an independent risk factor for in-hospital mortality in AIS patients admitted to ICU, which may help identify AIS patients with a higher risk of in-hospital mortality in the ICU.

Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8⁺ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.

Objective To investigate the effects of cyclic stretch on migration of MC3T3-E1 cells and its related mechanism. Methods The strain loading system was used to stretch MC3T3-E1 cells cultured in vitro with 15% amplitude, to simulate the mechanical condition in vivo. The wound healing assay was used to detect the migration of MC3T3-E1 cells. Western blotting was used to test Runx2 expression. RNA interfering was used to decrease Runx2 expression. Results Cyclic mechanical stretch with 15% amplitude, 1.25 Hz frequency and lasting for 24 hours could promote the migration of MC3T3-E1 cells and increase the expression level of Runx2. Runx2 interference inhibited the migration of MC3T3-E1 cells in static culture condition. Interference with Runx2 expression in MC3T3-E1 cells could partially reduce the positive effect of cyclic mechanical stretch on cell migration. Conclusions Cyclic stretch can promote the migration of MC3T3-E1 cells, and Runx2 may play an important role in this process. This study provides experimental basis for finding innovative clinical treatment method to promote fracture healing.

Chronic wounds in diabetes mellitus is a common complication of diabetes mellitus with complex pathogenesis and long recovery time. At present, there are many kinds of dressings for chronic wounds in diabetes, among which synthetic dressings have obvious therapeutic advantages. As an emerging biomaterial, hydrogel has obvious advantages over traditional dressings in terms of water absorption, air permeability, biocompatibility, drug loading ability, and continuous controlled drug release, and has attracted much attention in the repair of chronic wounds in diabetes mellitus. Common hydrogels have anti-inflammatory, antibacterial, antioxidant, tissue-promoting, and hypoglycemic effects. This paper systematically summarizes the progress in research on anti-inflammatory and antibacterial hydrogels in chronic diabetic wounds. Among them, according to different anti-inflammatory and antibacterial mechanisms and materials, common anti-inflammatory hydrogels can be divided into hydrogels loaded with anti-inflammatory drugs, hydrogels based on anti-inflammatory materials, and hydrogels loaded with biological components. Hydrogels can be classified into antibiotic-loaded hydrogels, antibacterial material-based hydrogels, and inorganic nanoparticles-loaded hydrogels. Anti-inflammatory and antibacterial hydrogels have achieved certain research results in the treatment of chronic diabetic wounds, but there are still some technical problems waiting for further improvement. Meanwhile, this paper discusses the prospect of the future development of hydrogels applied in chronic diabetic wounds, aiming to provide systematic theoretical support for the treatment of chronic diabetic wounds in the future.

Intrauterine adhesion (IUA) is caused by damage of the basal layer of endometrium, which leads to fibrosis of the endometrium and the formation of adhesion, resulting in partial or complete occlusion of the uterine cavity, abnormal menstruation, infertility or recurrent miscarriage. The prevalence of IUA in women has been increasing in recent years, and the high recurrence rate of moderate to severe IUA makes IUA treatment more challenging. Iatrogenic endometrial injury is the main cause of IUA. However, the incidence of IUA and the severity of IUA vary among patients who have received similar uterine operations, suggesting that there may be other synergistic factors in the development of IUA. There is a certain correlation between the pathogenesis and the microbiota of the gential tract. In many IUA patients, it has been observed that the probiotics such as Lactobacillus in the vagina is significant reduced, and the pathogenic bacteria such as Gardnerella and Prevotella are excessive growth. The reproductive tract microbiota can be involved in the development and progression of IUA via impacting immune function and metabolism.
Humans ; Female

Objective:To explore the effect of high-flow airway humidification on aspiration and residues in cases of dysphagia after a tracheotomy.Methods:Seventeen persons with dysphagia after a tracheotomy were asked to swallow 5ml of a thick liquid when their tracheal cannula was either connected to a high-flow airway humidification system or blocked, or the cuff was empty or full. Endoscopic evaluation was then used to grade the residue and aspiration in the different conditions.Results:There were significant differences in the residuals grading and aspiration among the four conditions. The average penetration-aspiration scale grade was significantly lower when the subject was connected to high-flow airway humidification than in the other three conditions. The grade of residuals was also significantly lower.Conclusion:High-flow airway humidification can effectively improve the swallowing of persons with dysphagia after a tracheotomy.

Objective:To explore the value of flexible endoscopic evaluation of swallowing (FEES) in guiding the decannulation of neurological disease patients with dysphagia after a tracheotomy.Methods:The FEES results of 188 neurological disease patients with dysphagia who had undergone a tracheotomy were analyzed retrospectively. The utility of FEES evaluation indexes (including glottis activity, the classification of pharyngeal secretions and residues as well as penetration-aspiration grade) for predicting the success of decannulation was explored.Results:One hundred and nine of the patients (the success group) were decannulated successfully and 79 (the failure group) were not, a success rate of 57%. The abnormal glottis activity rate among the failure group was 55%, significantly higher than among the success group (21%). The pharyngeal secretion classifications and penetration-aspiration grades among the success group were also significantly lower than among the failure group, on average. The average course of recovery from the tracheotomy was 184 days in the success group, significantly shorter than that of the failure group (292 days). No significant differences in residues were observed.Conclusion:The glottis activity, secretions and intake aspiration evaluated using FEES are of great value for guiding the decannulation of neurological disease patients with dysphagia after a tracheotomy.

Objective: To investigate the role and mechanism of Hydroxysafflor yellow A (HSYA) in the calcification of vascular smooth muscle cells (VSMC) induced by β-glycerol phosphate (β-GP). Methods: VSMC were cultured with 10% fetal bovine serum+1% double anti-high glucose DMEM medium at 37℃ and 5%CO₂ incubator, and were subcultured according to cell growth density at 1∶4 ratio. The cells were divided into three groups: control group (NC), high-phosphate-induced calcification (HP) group, and HSYA intervention (HSYA) group. The Calcium deposition amount was measured by alizarin red staining and calcium determination kit. The expressions of ALP, RUNX2, RANKL, α-SMA and inflammation indicators TLR4, TNF-α, IL-8 were detected by Western blotting method; Western blotting was also used to detect calcification index alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2). Nuclear factor kappa B receptor activating factor ligand(RANKL), α-smooth muscle actin (α-SMA), and the expressions of TLR4/NF-κB pathway and inflammatory response-related indicators Toll-like receptor 4 (TLR4), interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α). The nuclear protein and cytoplasmic proteins were respectively extracted. The expressions of p65 in nucleus and cytoplasm, as well as the expressions of p65 and phosphorylated p65 in total proteins were detected by Western blotting method. Superoxide dismutase (SOD) and malondialdehyde (MDA) kit were used to detect the content of antioxidant enzymes and oxidation end products in cells. Results: Western blotting showed that the expressions of ALP, RUNX2 and RANKL in HSYA group were significantly lower than that in HP group. The expression of α-SMA was increased than that of HP group (all P<0.01). The expression levels of TLR4, TNF-α, IL-8 and p-NF-κB/p65 in HSYA group were decreased compared with that in the HP group, and p65 was decreased in nucleus and increased in cytoplasm (all P<0.05). SOD content in HSYA group was significantly higher than that in HP group, and MDA content was significantly lower than that in HP group (all P<0.01). Conclusions HSYA can reduce calcification and calcium deposition of vascular smooth muscle cells induced by high phosphorus. The mechanism is related to the inhibition of the activation of TLR4/NF-κB pathway and the inhibition of oxidative stress.