Stem cell-derived exosomes in the treatment of melasma and its percutaneous penetration.

BACKGROUND AND OBJECTIVES: Melasma is a refractory skin disease due to its complex pathogenesis and difficult treatment. Studies have found that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) could serve as a novel cell-free therapeutic strategy in regenerative and esthetic medicine. It could potentially treat melasma, but the skin barrier is a challenge. In this study, we aim to explore the safety and efficacy of hUCMSC-Exos in the treatment of melasma and the means to promote its percutaneous penetration. MATERIALS AND METHODS: In the animal study about the effect of penetration, percutaneous penetration of PKH67-labeled hUCMSC-Exos was studied under microneedles, 1565 nm nonablative fractional laser (NAFL), and a plasma named Peninsula Blue Aurora Shumin Master (PBASM) treatments, observed by confocal laser scanning microscopy. In the clinical application study, 60 patients with melasma treated in our department were divided into four groups. NAFL combined with normal saline treatment was used for Group A. Microneedles, NAFL, and PBASM combined with hUCMSC-Exos treatments were used for Groups B, C, and D, respectively. Each patient received four treatments at 1-month intervals. Assessments were done using the degree of pain posttreatment, melasma area and severity score, improvement rate, physician global assessment score, satisfaction, and complications. RESULTS: In the animal study about the effect of penetration, hUCMSC-Exos can penetrate the deep dermis under microneedles, NAFL, and PBASM treatments. In the clinical application study, compared with Group A, Groups B, C, and D showed significantly improved therapeutic effect and patient satisfaction (p < 0.05), and there was no significant difference among Groups B, C, and D.(p > 0.05). Patients in Group B reported higher pain levels than those in the other three groups (p < 0.05); the treatment experience of patients in Group D was better. CONCLUSION: hUCMSC-Exos can improve the symptoms of melasma safely and effectively. Compared with microneedles, NAFL and PBASM can also achieve a good effect toward promoting penetration. These findings are worthy of exploration and clinical application.

CircWHSC1 serves as an oncogene to promote hepatocellular carcinoma progression.

BACKGROUND: Circular RNAs (circRNAs) function as vital regulators in multifarious cancers, including hepatocellular carcinoma (HCC). However, the roles of circRNA Wolf-Hirschhorn syndrome candidate gene-1 (circWHSC1) in HCC are barely known. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted for the levels of circWHSC1, miR-142-3p, miR-421, miR-665 and homeobox A1 (HOXA1) mRNA. Cell Counting Kit-8 (CCK-8) assay, colony formation assay and 5'-ethynyl-2'-deoxyuridine (EdU) assay were used to evaluate cell proliferation ability. Transwell assay was adopted for cell migration and invasion. Western blot assay was employed for protein levels. RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were executed to verify the interaction between miR-142-3p and circWHSC1 or HOXA1. Murine xenograft model assay was conducted for the role of circWHSC1 in vivo. The morphology of exosomes was observed by transmission electron microscopy (TEM). RESULTS: CircWHSC1 was elevated in HCC tissues and cells, and high level of circWHSC1 was associated with worse overall survival of HCC patients. Knockdown of circWHSC1 suppressed HCC cell proliferation and metastasis in vitro and restrained tumorigenesis in vivo. CircWHSC1 functioned as the sponge for miR-142-3p, which directly targeted HOXA1. Inhibition of miR-142-3p ameliorated the effects of circWHSC1 knockdown on HCC cell proliferation and metastasis. Moreover, miR-142-3p overexpression restrained the growth and motility of HCC cells, with HOXA1 elevation reversing the impacts. Additionally, circWHSC1 was increased in HCC patients' serum and might be a diagnostic indicator for HCC. CONCLUSION: CircWHSC1 played a tumour-promoting role in HCC by elevating HOXA1 through sponging miR-142-3p.

Effect of Oral Glucose Water Administration 1 Hour Preoperatively in Children with Cyanotic Congenital Heart Disease: A Randomized Controlled Trial.

BACKGROUND Guidelines recommend a clear liquid fasting time of 2 h before surgery, which is often exceeded, leading to adverse reactions (ARs) such as discomfort, thirst, and dehydration. We assessed the gastric contents and ARs after oral glucose water administration 1 h prior to surgery in children with cyanotic congenital heart disease (CCHD). MATERIAL AND METHODS This was a non-inferiority randomized controlled trial of children with CCHD enrolled at the Fujian Medical University Union Hospital from 09/2014 to 05/2017 and randomized to receive oral glucose water (10 g of glucose in 100 ml of warm water, 5 ml/kg) 2 h (2-h group, n=174) or 1 h (1-h group, n=170) before surgery. The primary endpoint was gastric volume. Secondary endpoints included pH of gastric content, preoperative blood glucose, and risk factors for aspiration pneumonia. Pre- and intraoperative ARs were recorded. RESULTS The 1-h group showed smaller gastric content volumes (0.34±0.35 (95% CI: 0.29-0.39) vs. 0.43±0.33 (95% CI: 0.38-0.48) ml/kg, t=2.55, P<0.05) and higher blood glucose (6.21±0.78 (95% CI: 6.09-6.33) vs. 5.59±1.11 (95% CI: 5.43-5.76) mmol/L, t=-5.91, P<0.001). The 95% confidence interval of the volume difference between the 2 groups was 0.017-0.163, the upper limit value was 0.163

A Predictive Nomogram for Intensive Care-Acquired Weakness after Cardiopulmonary Bypass.

PURPOSE: Intensive care unit-acquired weakness (ICUAW) affects patient prognosis after cardiopulmonary bypass (CPB) surgery, but its risk factors remain unclear. We investigated these risk factors and developed a nomogram for predicting ICUAW after CPB. METHODS: Baseline characteristics, preoperative laboratory data, and intra- and postoperative variables of 473 patients after CPB were determined in this prospective cohort study. Lower limb muscles on bedside ultrasound images were compared 1 day before and 7 days after CPB. Risk factors were assessed using logistic regression models. RESULTS: Approximately 50.95% of the patients developed ICUAW after CPB. The body mass index (BMI), New York Heart Association (NYHA) class, lactate, albumin, aortic clamping time, operation time, and acute physiological and chronic health evaluation II were determined as independent risk factors. The average absolute error of coincidence was 0.019; the area under the curve, sensitivity, and specificity were 0.811, 0.727, and 0.733, respectively, for the predictive nomogram. CONCLUSION: A high BMI, poor NYHA class, preoperative high serum lactate, low serum albumin, long surgical duration, aortic clamping, and high acute physiological and chronic health evaluation II score are risk factors for ICUAW after CPB. This robust and easy-to-use nomogram was developed for clinical decision-making.

On truth and polarity in negation processing: language-specific effects in non-linguistic contexts.

Introduction: This study examines how negation is processed in a nonverbal context (e.g., when assessing ▲ ≠ ▲) by speakers of a truth-based system like Mandarin and a polarity-based system like English. In a truth-based system, negation may take longer to process because it is typically attached to the negation as a whole (it is not true that triangle does not equal triangle), whereas in polarity-based systems, negation is processed relatively faster because it is attached to just the equation symbol (triangle does not equal triangle), which is processed relatively faster. Our hypothesis was that negation processing routines previously observed for verbal contexts, namely that speakers of Mandarin get slowed down more when processing negative stimuli than positive stimuli compared to speakers of English, also extend to contexts when language use is not obligatory. Methods: To test this, we asked participants to agree/disagree with equations comprising simple shapes and positive '=' or negative '≠' equation symbols. English speakers showed a response-time advantage over Mandarin speakers in negation conditions. In a separate experiment, we also tested the contribution of equation symbols '≠'/'=' to the cognitive demands by asking participants to judge shape sameness in symbol-free trials, such as ▲ ■. This comparison allowed us to test whether crosslinguistic differences arise not because of shape congruence judgement but arguably due to negation attachment. Results and discussion: The effect of the '≠' symbol on shape congruence was language-specific, speeding up English speakers but slowing down Mandarin speakers when the two shapes differed. These findings suggest language-specific processing of negation in negative equations, interpreted as novel support for linguistic relativity.

The occurrence of early atrial fibrillation after cardiac valve operation and the establishment of a nomogram model.

Background: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, which is associated with age and massive bleeding. However, whether thyroid hormone (TH) level can affect POAF remains controversial. Aim: To investigate the occurrence and risk factors of POAF, in particular, the preoperative TH level of patients was introduced into this study as a variable for analysis, and a column graph prediction model of POAF was constructed. Methods: Patients who underwent valve surgery in Fujian Cardiac Medical Center from January 2019 to May 2022 were retrospectively analyzed and divided into POAF group and NO-POAF group. Baseline characteristics and relevant clinical data were collected from the two groups of patients. Independent risk factors for POAF were screened using univariate analysis and binary logistic regression analysis, and a column line graph prediction model was established based on the regression analysis results, and the diagnostic efficacy and calibration of the model were evaluated using the Receiver Operating Characteristic Curve (ROC) and calibration curve. Results: A total of 2,340 patients underwent valve surgery, excluding 1,751 patients, a total of 589 patients were included, including 89 patients in POAF group and 500 patients in NO-POAF group. The total incidence of POAF was 15.1%. The results of the Logistics regression analysis showed that gender, age, leukocytes and TSH were risk factors of POAF. The area under the ROC curve of the nomogram prediction model for POAF was 0.747 (95% CI: 0.688-0.806, P < 0.001), with a sensitivity of 74.2% and specificity of 68%. Hosmer-Lemeshow test showed χ 2 = 11.141, P = 0.194 > 0.05, the calibration curve was well fitted. Conclusion: The results of this study show that gender, age, leukocyte and TSH are risk factors of POAF, and the nomogram prediction model has a good prediction effect. Due to the limited sample size and included population, more studies are needed to validate this result.

A multifunctional hydrogel loaded with two nanoagents improves the pathological microenvironment associated with radiation combined with skin wounds.

Persistent oxidative stress and recurring waves of inflammation with excessive reactive oxygen species (ROS) and free radical accumulation could be generated by radiation. Exposure to radiation in combination with physical injuries such as wound trauma would produce a more harmful set of medical complications, which was known as radiation combined with skin wounds (RCSWs). However, little attention has been given to RCSW research despite the unsatisfactory therapeutic outcomes. In this study, a dual-nanoagent-loaded multifunctional hydrogel was fabricated to ameliorate the pathological microenvironment associated with RCSWs. The injectable, adhesive, and self-healing hydrogel was prepared by crosslinking carbohydrazide-modified gelatin (Gel-CDH) and oxidized hyaluronic acid (OHA) through the Schiff-base reaction under mild condition. Polydopamine nanoparticles (PDA-NPs) and mesenchymal stem cell-secreted small extracellular vesicles (MSC-sEV) were loaded to relieve radiation-produced tissue inflammation and oxidation impairment and enhance cell vitality and angiogenesis individually or jointly. The proposed PDA-NPs@MSC-sEV hydrogel enhanced cell vitality, as shown by cell proliferation, migration, colony formation, and cell cycle and apoptosis assays in vitro, and promoted reepithelization by attenuating microenvironment pathology in vivo. Notably, a gene set enrichment analysis of proteomic data revealed significant enrichment with adipogenic and hypoxic pathways, which play prominent roles in wound repair. Specifically, target genes were predicted based on differential transcription factor expression. The results suggested that MSC-sEV- and PDA-NP-loaded multifunctional hydrogels may be promising nanotherapies for RCSWs. STATEMENT OF SIGNIFICANCE: The small extracellular vesicle (sEV) has distinct advantages compared with MSCs, and polydopamine nanoparticles (PDA-NPs), known as the biological materials with good cell affinity and histocompatibility which have been reported to scavenge ROS free radicals. In this study, an adhesive, injectable, self-healing, antibacterial, ROS scavenging and amelioration of the radiation related microenvironment hydrogel encapsulating nanoscale particles of MSC-sEV and PDA-NPs (PDA-NPs@MSC-sEV hydrogel) was synthesized for promoting radiation combined with skin wounds (RCSWs). GSEA analysis profiled by proteomics data revealed significant enrichments in the regulations of adipogenic and hypoxic pathways with this multi-functional hydrogel. This is the first report of combining this two promising nanoscale agents for the special skin wounds associated with radiation.

Single-Cell and Spatial Transcriptomics Decodes Wharton's Jelly-Derived Mesenchymal Stem Cells Heterogeneity and a Subpopulation with Wound Repair Signatures.

The highly heterogeneous characteristics of Wharton's jelly mesenchymal stem cells (WJ-MSCs) may be responsible for the poor clinical outcomes and poor reproducibility of treatments based on WJ-MSCs. Exploration of WJ-MSC heterogeneity with multimodal single-cell technologies will aid in establishing accurate MSC subtyping and developing screening protocols for dominant functional subpopulations. Here, the characteristics of WJ-MSCs are systematically analyzed by single cell and spatial transcriptome sequencing. Single-cell transcriptomics analysis identifies four WJ-MSC subpopulations, namely proliferative_MSCs, niche-supporting_MSCs, metabolism-related_MSCs and biofunctional-type_MSCs. Furthermore, the transcriptome, cellular heterogeneity, and cell-state trajectories of these subpopulations are characterized. Intriguingly, the biofunctional-type MSCs (marked by S100A9, CD29, and CD142) selected in this study exhibit promising wound repair properties in vitro and in vivo. Finally, by integrating omics data, it has been found that the S100A9+ CD29+ CD142+ subpopulation is more enriched in the fetal segment of the umbilical cord, suggesting that this subpopulation deriving from the fetal segment may have potential for developing into an ideal therapeutic agent for wound healing. Overall, the presented study comprehensively maps the heterogeneity of WJ-MSCs and provides an essential resource for future development of WJ-MSC-based drugs.

Identifying pancreatic cancer-associated miRNAs using weighted gene co-expression network analysis.

Pancreatic cancer is a common type of gastrointestinal tumour throughout the world and is characterised by high malignancy rates and poor prognosis. Studies indicated that early and effective diagnosis is key to prolonging patients' overall survival, particularly in the case of fluid biopsy. Given this, the present study was designed to evaluate the expression profile arrays of patients with pancreatic cancer from the Gene Expression Omnibus database in an effort to identify differentially expressed microRNAs (miRNAs/miRs) that may be suitable for application in liquid biopsy-based diagnostics. Suitable miRNA candidates were identified using a weighted correlation network analysis (WGCNA) and key differentially expressed miRNAs were verified using reverse transcription-quantitative PCR. WGCNA identified 11 differentially expressed miRNAs (miR-155-5p, miR-4668-5p, miR-3613-3p, miR-3201, miR-548ac, miR-486-5p, miR-548a-3p, miR-8084, miR-455-3p, miR-6068 and miR-1246). Of these, miR-4668-5p was indicated to have the highest number of associated modules, making it most likely to be of diagnostic value. Thus, the present analysis identified 11 miRNAs associated with pancreatic cancer and further identified miR-4668-5p as a potential biomarker for pancreatic cancer diagnosis.

Family-centred care interventions to reduce the delirium prevalence in critically ill patients: A systematic review and meta-analysis.

AIM: This study aimed to determine whether family-centred care (FCC) intervention reduces the ICU delirium prevalence. DESIGN: A systematic review and meta-analysis. METHODS: The databases, including PubMed, Cochrane Central Register of Controlled Trials, Web of Science, CINAHL Complete, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBMdisc), WANFANG Data and VIP Information, were systematically searched up to 30 November 2021. The search term includes keywords related to intensive care units, delirium and family-centred care. Meta-analyses were performed and presented by risk ratio (RR), mean difference (MD) and corresponding 95% confidence intervals (CIs). RESULTS: The meta-analysis results showed that compared with the usual care, FCC intervention has positive effects on reducing ICU delirium prevalence [RR = 0.54, 95% CIs (0.36, 0.81), p < .05]. However, no effect was observed on ICU stays, mechanical ventilation duration and ICU-acquired infection between the two groups. CONCLUSIONS: Family-centred care is an effective intervention to reduce the ICU delirium prevalence. But the result should be treated cautiously as the high levels of heterogeneity, further high-quality studies are required to determine the effectiveness of FCC intervention in the ICU setting.

Wharton's jelly mesenchymal stem cell-derived small extracellular vesicles as natural nanoparticles to attenuate cartilage injury via microRNA regulation.

The main strategy of tissue repair and regeneration focuses on the application of mesenchymal stem cells and cell-based nanoparticles, but there are still multiple challenges that may have negative impacts on human safety and therapeutic efficacy. Cell-free nanotechnology can effectively overcome these obstacles and limitations. Mesenchymal stem cell (MSC)-derived natural small extracellular vesicles (sEVs) represent ideal nanotherapeutics due to their low immunogenicity and lack of tumorigenicity. Here, sEVs harvested from Wharton's jelly mesenchymal stem cells (WJMSCs) were identified. In vitro results showed that WJMSC-sEVs efficiently entered chondrocytes in the osteoarthritis (OA) model, further promoted chondrocyte migration and proliferation and modulated immune reactivity. In vivo, WJMSC-sEVs notably promoted chondrogenesis, which was consistent with the effect of WJMSCs. RNA sequencing results revealed that sEV-microRNA-regulated biocircuits can significantly contribute to the treatment of OA, such as by promoting the activation of the calcium signaling pathway, ECM-receptor interaction pathway and NOTCH signaling pathway. In particular, let-7e-5p, which is found in WJMSC-sEVs, was shown to be a potential core molecule for promoting cartilage regeneration by regulating the levels of STAT3 and IGF1R. Our findings suggest that WJMSC-sEV-induced chondrogenesis is a promising innovative and feasible cell-free nanotherapy for OA treatment.

A multidisciplinary team nursing model in the treatment of patients undergoing transapical mitral valve clamping: a prospective study.

BACKGROUND: As a new surgical method for older adults with cardiac insufficiency, transapical mitral valve clamp surgery requires the cooperation of practitioners across multiple disciplines to ensure appropriate treatment and nursing care. This study aimed to explore the utility of a multidisciplinary team nursing model in the clinical treatment and nursing care of patients undergoing transapical mitral valve clamping. METHODS: Our sample of ten patients included four men (40%) and six women (60%), with a mean age of 71.4 ± 5.2 years. The multidisciplinary team comprised nurses that specialized in severe illness, cardiac health, rehabilitation, psychology, nutrition, and pain. The team engaged in comprehensive discussions regarding problems specific to the patients undergoing transapical mitral valve surgery, allowing them to formulate individualized nursing measures and implement precise policies. RESULTS: No serious postoperative complications occurred in any of the ten patients included in this study, and a significant improvement was noted in the cardiac status of all the patients. Color ultrasound findings at discharge indicated that the degree of reflux of all the patients was ≤2+. Among the ten patients, the Activity of Daily Living Scale scores at discharge were significantly higher than before the operation (69.0 ± 4.6 vs. 55.0 ± 5.8). In addition, the 6-min walking test results at discharge were significantly better than those observed before the operation (318.0 ± 21.7 m vs. 295.2 ± 18.4 m). CONCLUSIONS: Utilization of a multidisciplinary team allows nurses across various specialties to provide more comprehensive and systematic care for patients undergoing a mitral valve clamping operation, thus promoting patient recovery.

RéSUMé: CONTEXTE: en tant que nouvelle méthode chirurgicale pour le traitement de l'insuffisance cardiaque chez les personnes âgées, la chirurgie par pince de la valve mitral aiguë nécessite la collaboration de médecins multidisciplinaires pour assurer un traitement et des soins appropriés. OBJECTIFS: étudier l'application du modèle de soins en équipe multidisciplinaire dans le traitement clinique et les soins aux patients atteints de la valve mitral par pince. MéTHODE: sur 10 patients, 4 hommes (40%) et 6 femmes (60%) ont un âge moyen de 71.4 à 5.2 ans. L'équipe multidisciplinaire est. composée d'infirmiers spécialisés dans les maladies graves, la santé cardiaque, la réadaptation, la psychologie, la nutrition et la douleur. L'équipe a mené une discussion approfondie sur les problèmes spécifiques des patients soumis à une opération de la valve mitral transspiroptérale, a élaboré des mesures de soins personnalisées et a mis en œuvre des politiques précises. RéSULTATS: aucune complication postoperatoire grave n'a été observée chez les 10 patients de ce groupe, et les défaillances cardiaques ont été nettement améliorées chez tous les patients. Une double échographie en couleur a montré que le degré de regurgitation mitral était inférieur ou égal à 2+ dans 10 patients sortant de cette étude; Les scores sur l'échelle des activités de la vie quotidienne à la sortie de l'hôpital étaient nettement plus élevés dans 10 cas que dans le cas préopératoire (69.0 ± 4.6 contre 55.0 ± 5.8). En outre, les résultats d'un essai de marche de 6 min à la sortie de l'hôpital étaient nettement supérieurs à ceux observés avant l'opération (318.0 ± 21.7 m contre 295.2 ± 18.4 m). CONCLUSION: le recours à des équipes multidisciplinaires permet aux infirmiers/infirmières spécialisés de fournir des soins plus complets et systématiques aux patients soumis à la chirurgie par compression de la valve mitral, ce qui facilite leur réadaptation.

Hierarchical pore structure based on cellulose nanofiber/melamine composite foam with enhanced sound absorption performance.

For the preparation of high-performance sound absorption materials, the fabrication of hierarchical pore structure has proven to be an effective way. Herein, cellulose nanofiber (CNF) and melamine foam (MF) were combined by an environmentally friendly method for the first time, which endowed the final composite foam with both macropores and mesopores. The hierarchical pore structure was constructed by cyclic freezing-thawing, which enhanced the multiple reflections and micro-vibration of the sound waves, resulting in an obvious improvement in sound absorption performance. Specifically, compared with the unmodified MF, the sound absorption performance of composite foam with a thickness of 20 mm at 0.4 wt% CNF concentration showed an enhancement of about 107 % at 500 Hz and the NRC (noise reduction coefficient) had an improvement of 80 %. This work is expected to provide more inspiration for the design and preparation of high-performance sound absorption materials.

Association between glucose variability and postoperative delirium in acute aortic dissection patients: an observational study.

BACKGROUND: Blood glucose variability is associated with poor prognosis after cardiac surgery, but the relationship between glucose variability and postoperative delirium in patients with acute aortic dissection is unclear. The study aims to investigate the association of blood glucose variability with postoperative delirium in acute aortic dissection patients. METHODS: We prospectively analyzed 257 patients including 103 patients with delirium. The patients were divided into two groups according to whether delirium was present. The outcome measures were postoperative delirium, the length of the Intensive Care Unit stay, and the duration of hospital stay. Multivariable Cox competing risk survival models was used to assess. RESULTS: A total of 257 subjects were enrolled, including 103 patients with delirium. There were statistically significant differences between the two groups in body mass index, history of cardiac surgery, first admission blood glucose, white blood cell counts, Acute Physiology and Chronic Health Evaluation II score, hypoxemia, mechanical ventilation duration, and the length of Intensive Care Unit stay(P < 0.05). The delirium group exhibited significantly higher values of the mean of blood glucose (MBG) and the standard deviation of blood glucose (SDBG) than in the non-delirium group(P < 0.05). In model 1, the adjusted hazard ratio (AHR) of the standard deviation of blood glucose was 1.436(P < 0.05). In Model 2, the standard deviation of blood glucose (AHR = 1.418, 95%CI = 1.195-1.681, P < 0.05) remained significant after adjusting for confounders. The area under the curve of the SDBG was 0.763(95%CI = 0.704-0.821, P < 0.01). The sensitivity was 81.6%, and the specificity was 57.8%. CONCLUSIONS: Glucose variability is associated with the risk of delirium in patients after aortic dissection surgery, and high glycemic variability increases the risk of postoperative delirium.

Small extracellular vesicles from human adipose-derived mesenchymal stromal cells: a potential promoter of fat graft survival.

BACKGROUND: Small extracellular vesicles (sEVs) with genetic information secreted by cells play a crucial role in the cellular microenvironment. In this study, our purpose is to explore the characteristics of the small extracellular vesicles of human adipose-derived mesenchymal stromal cells (hADMSC-sEVs) and studied the role of hADMSC-sEVs in improving the survival rate of grafted fat. METHODS: In the present study, we used the transmission electron microscopy, nano-tracking analysis, nanoflow surface protein analysis, and zeta potential value to identify sEVs. SEVs' trajectory was traced dynamically to verify whether hADMSC-sEVs can be internalized into human umbilical vein endothelial cells (HUVECs) in vitro at different times. The angiogenic property of hADMSC-sEVs was observed by measuring the volume, weight, and histological analysis of the grafted fats in nude mouse models. RESULTS: Our research showed that the hADMSC-sEVs were sEVs with double-layer membrane structure and the diameter of which is within 30-150 nm. hADMSC-sEVs exert biological influence mainly through internalization into cells. Compared with the control group, the hADMSC-sEVs group had a significantly higher survival rate of grafted fat, morphological integrity, and a lower degree of inflammation and fibrosis. And immunohistochemistry showed that hADMSC-sEVs significantly increased the neovascularisation and the expression of CD34, VEGFR2, and Ki-67 in the graft tissue. CONCLUSIONS: As a potential nanomaterial, hADMSC-sEVs have been explored in the field of cell-free application of stem cell technology. hADMSC-sEVs promoted the survival of grafted fats by promoting the formation of new blood vessels, which is another promising progress in the field of regenerative medicine. We believe that hADMSC-sEVs will have a broad application prospect in the field of regenerative medicine in the future.

Combination of lyophilized adipose-derived stem cell concentrated conditioned medium and polysaccharide hydrogel in the inhibition of hypertrophic scarring.

BACKGROUND: Mesenchymal stem cell-based acellular therapies have been widely exploited in managing hypertrophic scars. However, low maintenance dose and transitory therapeutic effects during topical medication remain a thorny issue. Herein, this study aimed to optimize the curative effect of adipose-derived stem cell conditioned medium (ADSC-CM) in the prevention of hypertrophic scarring. METHODS: In the present study, ADSC-CM was concentrated via the freeze-drying procedure. The efficacy of different dose groups (CM, CM5, CM10) was conducted on the proliferation, apoptosis, and α-smooth muscle actin (α-SMA) expression of human keloid fibroblasts (HKFs) in vitro. Incorporation of adipose-derived stem cell concentrated conditioned medium (ADSCC-CM) into polysaccharide hydrogel was investigated in rabbit ear, in vivo. Haematoxylin-eosin (H&E) and Masson's trichrome staining were performed for the evaluation of scar hyperplasia. RESULTS: We noted that ADSCC-CM could downregulate the α-SMA expression of HKFs in a dose-dependent manner. In the rabbit ear model, the scar hyperplasia in the medium-dose group (CM5) and high-dose group (CM10) was inhibited with reduced scar elevation index (SEI) under 4 months of observation. It is noteworthy that the union of CM5 and polysaccharide hydrogel (CM5+H) yielded the best preventive effect on scar hyperplasia. Briefly, melanin, height, vascularity, and pliability in the CM5+H group were better than those of the control group. Collagen was evenly distributed, and skin appendages could be regenerated. CONCLUSIONS: Altogether, ADSCC-CM can downregulate the expression of α-SMA due to its anti-fibrosis effect and promote the rearrangement of collagen fibres, which is integral to scar precaution. The in situ cross bonding of ADSCC-CM and polysaccharide hydrogel could remarkably enhance the therapeutic outcomes in inhibiting scar proliferation. Hence, the alliance of ADSCC-CM and hydrogel may become a potential alternative in hypertrophic scar prophylaxis.

Comparison of Curative Effect of Human Umbilical Cord-Derived Mesenchymal Stem Cells and Their Small Extracellular Vesicles in Treating Osteoarthritis.

INTRODUCTION: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their small extracellular vesicles (hUC-MSC-sEVs) have shown attractive prospects applying in regenerative medicine. This study aimed to compare the therapeutic effects of two agents on osteoarthritis (OA) and investigate underlying mechanism using proteomics. METHODS: In vitro, the proliferation and migration abilities of chondrocytes treated with hUC-MSCs or hUC-MSC-sEVs were detected by Cell Counting Kit-8 assay and scratch wound assay. In vivo, hUC-MSCs (a single dose of 5 × 105) or hUC-MSC-sEVs (30 µg/time) were injected into the knee joints of anterior cruciate ligament transection-induced OA model. Hematoxylin and eosin, Safranin O/Fast Green staining were used to observe cartilage degeneration. The levels of cartilage matrix metabolic molecules (Collagen II, MMP13 and ADAMTS5) and macrophage polarization markers (CD14, IL-1ß, IL-10 and CD206) were assessed by immunohistochemistry. Finally, proteomics analysis was performed to characterize the proteinaceous contents of two agents. RESULTS: In vitro data showed that hUC-MSC-sEVs were taken up by chondrocytes. A total of 15 µg/mL of sEVs show the greatest proliferative and migratory capacities among all groups. In the animal study, hUC-MSCs and hUC-MSC-sEVs alleviated cartilage damage. This effect was mediated via maintaining cartilage homeostasis, as was confirmed by upregulation of the COL II and downregulation of the MMP13 and ADAMTS5. Moreover, the M1 macrophage markers (CD14) were significantly reduced, while the M2 macrophage markers (CD206 and IL-10) were increased in the hUC-MSCs and hUC-MSC-sEVs relative to the untreated group. Mechanistically, we found that many proteins connected to cartilage repair were more abundant in sEVs. Notably, compared to hUC-MSCs, the upregulated proteins in sEVs were mostly involved in the regulation of immune effector process, extracellular matrix organization, PI3K-AKT signaling pathways, and Rap1 signaling pathway. CONCLUSION: Our study indicated that hUC-MSC-sEVs protect cartilage from damage and many cartilage repair-related proteins are probably involved in the restoration process. These data suggest the promising potential of hUC-MSC-sEVs as a therapeutic agent for OA.

Relationship of Platelet Counts and Inflammatory Markers to 30-Day Mortality Risk in Patients with Acute Type A Aortic Dissection.

Markers of prothrombotic state and inflammation are associated with the prognosis of patients with acute type A aortic dissection (AAAD). However, it is unclear that the relationship between these biomarkers and their combined impact on risk stratification. The present study evaluated the prognostic value of platelet counts, lymphocyte to neutrophil ratio (LNR), and lymphocyte to monocyte ratio (LMR), alone and in combination. A retrospective analysis of clinical data of 744 AAAD patients was conducted to identify whether these biomarkers were related to the 30-day mortality risk. A Kaplan-Meier analysis and log-rank test were used to compare survival between groups. A Cox hazard regression multivariable analysis was performed for 30-day mortality. Individual biomarker (platelet count, LNR, or LMR) was unable to predict 30-day mortality. However, combinations of all three biomarkers provided additive predictive value over either marker alone, the receiver operating characteristic (ROC) model had a prediction probability of 0.739 when platelet counts, LNR, and LMR were included. Cox hazard regression multivariable analysis showed that combinations of all three biomarkers were the strongest predictor of 30-day mortality (p < 0.021). Combined with these three easily measurable biomarkers at admission, they could help identify AAAD patients with a high risk of 30-day mortality.

Sex differences in factors associated with post-traumatic stress disorder in acute type A aortic dissection patients.

BACKGROUND: Emergency surgery for acute type A aortic dissection (AAAD) is associated with a high risk for posttraumatic stress disorder (PTSD), and the risk factors for PTSD symptoms development in AAAD patients of different sexes remain unclear. OBJECTIVE: To identify the risk factors for PTSD symptoms separately in the females and males following AAAD. METHODS: A sample population of 214 patients who had AAAD surgery was recruited. Patients' sociodemographic and disease-specific data were collected during hospitalization. RESULTS: In this study, PTSD symptoms was present in 22.1% of the male patients and 20.0% of the female patients (P = 0.739). For the male patients with AAAD, PTSD symptoms were significantly positively associated with HADS-D score (P = 0.029), while those with university education and above (P = 0.039), stronger subjective support (P = 0.010) and greater optimism (P = 0.001) had significantly lower possibility for the presence of PTSD symptoms. For the female patients with AAAD, support availability (P = 0.031) was significantly negatively associated with PTSD symptoms while HADS-D score (P = 0.033) was significantly positively associated with PTSD symptoms. CONCLUSION: Risk factors for PTSD symptoms differ in male patients and female patients following AAAD.

Predictors of return to work after open triple-branched stent graft placement for acute type A aortic dissection.

OBJECTIVES: To investigate the rate of returning to work within 12 months after open triple-branched stent graft placement in acute type A aortic dissection (AAAD) patients and the reasons why patients did not return to work. METHODS: We conducted this cohort study of AAAD patients who were discharged alive from the hospital at Fujian Cardiac Center during the period 2013-2018. The collected data included the patients' baseline characteristics, employment status at 12 months after AAAD and variables classifying the potential reasons for those who did not return to work at 12 months. We applied logistic regression to estimate the factors associated with returning to work at 12 months. RESULTS: One year after AAAD hospitalization, of the 326 AAAD patients, 81 (24.8%) returned to work, 231 (70.9%) did not and 14 (4.3%) died. Among the 231 patients who did not return to work, 105 (45.5%) were unable to work because of AAAD and 36 (15.6%) lost job owing to AAAD. After adjustment for other risk factors, age, female sex, type of work, operating time, aortic cross-clamp time and length of intensive care unit (ICU) stay were still significantly associated with a lower chance of returning to work. CONCLUSIONS: Less than 25% of the previously employed patients returned to work at 12 months after AAAD. Older age, female sex, manual or semi-skilled professional work, a longer operating time, a longer aortic cross-clamp time and a longer length of ICU stay were associated with a lower likelihood of returning to work.