Effects of mild hyperbaric oxygen therapy on timing sequence recovery of muscle fatigue in chinese university male athletes.

Objectives: This study aimed to investigate the timing sequence recovery effects of single and repeated Mild Hyperbaric Oxygen Therapy (MHOT) on muscle fatigue induced by cycling exercise through a comprehensive set of parameters. Methods: This study employed a controlled crossover design involving 12 Chinese secondary national-level male athletes. Each participant completed two identical trials over six days. Each trial consisted of a 90-min cycling exercise followed by either a Control (CON) intervention (1 atm absolute (ATA), 20.9 % oxygen, 60 min) or MHOT intervention (1.25 ATA, 26%-28 % oxygen, 60 min). Various physiological parameters including Rating of Perceived Exertion (RPE), Heart Rate (HR), Peripheral Oxygen Saturation (SpO2), Perfusion Index (PI%), Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Lactic Acid (LA), Blood Urea Nitrogen (BUN), Superoxide Dismutase (SOD), Malondialdehyde (MDA), and Standing Long Jump Distance (SLJ) were measured at six different time points throughout the trials. Results: RPE revealed that the MHOT group experienced reduced subjective fatigue in comparison to the CON group (P < 0.05). Additionally, MHOT demonstrated quicker recovery in HR and PI% compared to the CON group (P < 0.05). Regarding CK, LA, BUN, SOD, and MDA levels, the MHOT group exhibited accelerated recovery post-6 intervention and at the 24-h mark after six interventions, showing significant improvement over the CON group (P < 0.05). However, no notable disparity was observed between groups concerning SpO2, LDH, and SLJ. Conclusions: Both single and repeated sessions of MHOT demonstrated efficacy in alleviating subjective fatigue and promoting recovery of heart rate and blood perfusion following muscle fatigue, ensuring parallel structure and consistency in their effects. Repeated MHOT sessions (six times) exhibit a significant reduction in levels of blood markers associated with muscle damage, metabolites, and oxidative stress. However, the impact of a single MHOT intervention was less pronounced.

Oligomeric Amyloid-ß and Tau Alter Cell Adhesion Properties and Induce Inflammatory Responses in Cerebral Endothelial Cells Through the RhoA/ROCK Pathway.

Dysfunction of cerebral endothelial cells (CECs) has been implicated in the pathology of Alzheimer's disease (AD). Despite evidence showing cytotoxic effects of oligomeric amyloid-ß (oAß) and Tau (oTau) in the central nervous system, their direct effects on CECs have not been fully investigated. In this study, we examined the direct effects of oAß, oTau, and their combination on cell adhesion properties and inflammatory responses in CECs. We found that both oAß and oTau increased cell stiffness, as well as the p-selectin/Sialyl-LewisX (sLeX) bonding-mediated membrane tether force and probability of adhesion in CECs. Consistent with these biomechanical alterations, treatments with oAß or oTau also increased actin polymerization and the expression of p-selectin at the cell surface. These toxic oligomeric peptides also triggered inflammatory responses, including upregulations of p-NF-kB p65, IL-1ß, and TNF-α. In addition, they rapidly activated the RhoA/ROCK pathway. These biochemical and biomechanical changes were further enhanced by the treatment with the combination of oAß and oTau, which were significantly suppressed by Fasudil, a specific inhibitor for the RhoA/ROCK pathway. In conclusion, our data suggest that oAß, oTau, and their combination triggered subcellular mechanical alterations and inflammatory responses in CECs through the RhoA/ROCK pathway.

Serum PYCARD may become a new diagnostic marker for rheumatoid arthritis patients.

BACKGROUND: The objective of this investigation is to analyze the levels and clinical relevance of serum PYCARD (Pyrin and CARD domain-containing protein, commonly known as ASC-apoptosis-associated speck-like protein containing a caspase activation and recruitment domain), interleukin-38 (IL-38), and interleukin-6 (IL-6) in individuals afflicted with rheumatoid arthritis (RA). METHODS: Our study comprised 88 individuals diagnosed with RA who sought medical attention at the Affiliated Hospital of Chengde Medical University during the period spanning November 2021 to June 2023, constituting the test group. Additionally, a control group of 88 individuals who underwent health assessments at the same hospital during the aforementioned timeframe was included for comparative purposes. The study involved the assessment of IL-38, IL-6, PYCARD, anti-cyclic citrullinated peptide antibody (anti-CCP), and erythrocyte sedimentation rate (ESR) levels in both groups. The research aimed to explore the correlations and diagnostic efficacy of these markers, employing pertinent statistical analyses for comprehensive evaluation. RESULTS: The test group had higher expression levels of PYCARD, IL-6, and IL-38 than the control group (P < 0.05). Based on the correlation analysis, there was a strong relationship between PYCARD and IL-38 (P < 0.01). The receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values of 0.97, 0.96, and 0.96 when using combinations of PYCARD and anti-CCP, IL-38 and anti-CCP, and IL-6 and anti-CCP for predicting RA, respectively. Importantly, all three of these pairs demonstrated superior AUC values compared to PYCARD, IL-38, IL-6, ESR, or anti-CCP used as standalone diagnostic indicators. CONCLUSION: PYCARD, IL-6, and IL-38 exhibit promising potential as novel diagnostic markers and may constitute valuable tools for supporting the diagnosis of RA.

Inhibition of Anaplastic Lymphoma Kinase Protects From Ischemic Stroke.

BACKGROUND: Ischemic stroke is often accompanied by oxidative stress and inflammatory response, both of which work synergistically to exacerbate the disruption of the blood-brain barrier and ischemic brain injury. ALK (anaplastic lymphoma kinase), a cancer-associated receptor tyrosine kinase, was found to play a role in oxidative stress and inflammation. In this study, we investigated the role of ALK inhibition in a murine model of ischemic stroke. METHODS: Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery in mice with a filament. The ALK inhibitor alectinib was administered following the stroke. ALOX15 (arachidonic acid 15-lipoxygenase) was overexpressed by adenovirus injection. The immunohistochemistry, Western blot, oxidative stress, inflammation, blood-brain barrier leakage, infarct volume, and functional outcomes were determined. RESULTS: We found that the expression of ALK was markedly increased in the neurovascular unit after cerebral ischemia. Treatment with the ALK inhibitor alectinib reduced the accumulation of reactive oxygen species, lipid peroxidation, and oxidative DNA, increased the vascular levels of antioxidant enzymes, inactivated the vascular NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome pathway, and reduced vascular inflammation (ICAM-1 [intercellular adhesion molecule-1] and MCP-1 [monocyte chemoattractant protein-1]) after ischemia. Moreover, alectinib reduced the loss of cerebrovascular integrity and blood-brain barrier damage, consequently decreasing brain infarction and neurological deficits. Furthermore, alectinib reduced stroke-evoked ALOX15 expression, whereas virus-mediated overexpression of ALOX15 abolished alectinib-dependent inhibition of oxidative stress and vascular inflammation, blood-brain barrier protection, and neuroprotection, suggesting the protective effects of alectinib for stroke may involve ALOX15. CONCLUSIONS: Our findings demonstrated that alectinib protects from stroke by regulating ischemic signaling cascades and suggest that ALK may be a novel therapeutic target for ischemic stroke.

The LPS-inactivating enzyme acyloxyacyl hydrolase protects the brain from experimental stroke.

Blood-brain-barrier (BBB) disruption is a pathological hallmark of ischemic stroke, and inflammation occurring at the BBB contributes to the pathogenesis of ischemic brain injury. Lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, is elevated in patients with acute stroke. The activity of LPS is controlled by acyloxyacyl hydrolase (AOAH), a host enzyme that deacylates LPS to inactivated forms. However, whether AOAH influences the pathogenesis of ischemic stroke remain elusive. We performed in vivo experiments to explore the role and mechanism of AOAH on neutrophil extravasation, BBB disruption, and brain infarction. We found that AOAH was upregulated in neutrophils in peri-infarct areas from mice with transient focal cerebral ischemia. AOAH deficiency increased neutrophil extravasation into the brain parenchyma and proinflammatory cytokine production, broke down the BBB and worsened stroke outcomes in mice. These effects require Toll-like receptor 4 (TLR4) because absence of TLR4 or pharmacologic inhibition of TLR4 signaling prevented the exacerbated inflammation and BBB damage in Aoah-/- mice after ischemic stroke. Importantly, neutrophil depletion or inhibition of neutrophil trafficking by blocking LFA-1 integrin dramatically reduced stroke-induced BBB breakdown in Aoah-/- mice. Furthermore, virus-mediated overexpression of AOAH induced a substantial decrease in neutrophil recruitment that was accompanied by reducing BBB damage and stroke volumes. Our findings show the importance of AOAH in regulating neutrophil-dependent BBB breakdown and cerebral infarction. Consequently, strategies that modulate AOAH may be a new therapeutic approach for treatment of ischemic stroke.

Long-term observation of polycaprolactone small-diameter vascular grafts with thickened outer layer and heparinized inner layer in rabbit carotid arteries.

In our previous study, the pristine bilayer small-diameterin situtissue engineered vascular grafts (pTEVGs) were electrospun from a heparinized polycaprolactone (PCL45k) as an inner layer and a non-heparinized PCL80k as an outer layer in the thickness of about 131 µm and 202 µm, respectively. However, the hydrophilic enhancement of inner layer stemmed from the heparinization accelerated the degradation of grafts leading to the early formation of arterial aneurysms in a period of 3 months, severely hindering the perennial observation of the neo-tissue regeneration, host cell infiltration and graft remodeling in those implanted pTEVGs. Herein to address this drawback, the thickness of the outer layers was increased with PCL80k to around 268 µm, while the inner layer remained unchangeable. The thickened TEVGs named as tTEVGs were evaluated in six rabbits via a carotid artery interpositional model for a period of 9 months. All the animals kept alive and the grafts remained patent until explantation except for one whose one side of arterial blood vessels was occluded after an aneurysm occurred at 6 months. Although a significant degradation was observed in the implanted grafts at 9 month, the occurrence of aneurysms was obviously delayed compared to pTEVGs. The tissue stainings indicated that the endothelial cell remodeling was substantially completed by 3 months, while the regeneration of elastin and collagen remained smaller and unevenly distributed in comparison to autologous vessels. Additionally, the proliferation of macrophages and smooth muscle cells reached the maximum by 3 months. These tTEVGs possessing a heparinized inner layer and a thickened outer layer exhibited good patency and significantly delayed onset time of aneurysms.

Better Life's Essential 8 contributes to slowing the biological aging process: a cross-sectional study based on NHANES 2007-2010 data.

Objective: To investigate the relationship between Life's Essential 8 (LE8) and Phenotypic Age Acceleration (PhenoAgeAccel) in United States adults and to explore the impact of LE8 on phenotypic biological aging, thereby providing references for public health policies and health education. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2010, this cross-sectional study analyzed 7,339 adults aged 20 and above. Comprehensive assessments of LE8, PhenoAgeAccel, and research covariates were achieved through the integration of Demographics Data, Dietary Data, Laboratory Data, and Questionnaire Data derived from NHANES. Weighted generalized linear regression models and restricted cubic spline plots were employed to analyze the linear and non-linear associations between LE8 and PhenoAgeAccel, along with gender subgroup analysis and interaction effect testing. Results: (1) Dividing the 2007-2010 NHANES cohort into quartiles based on LE8 unveiled significant disparities in age, gender, race, body mass index, education level, marital status, poverty-income ratio, smoking and drinking statuses, diabetes, hypertension, hyperlipidemia, phenotypic age, PhenoAgeAccel, and various biological markers (p < 0.05). Mean cell volume demonstrated no intergroup differences (p > 0.05). (2) The generalized linear regression weighted models revealed a more pronounced negative correlation between higher quartiles of LE8 (Q2, Q3, and Q4) and PhenoAgeAccel compared to the lowest LE8 quartile in both crude and fully adjusted models (p < 0.05). This trend was statistically significant (p < 0.001) in the full adjustment model. Gender subgroup analysis within the fully adjusted models exhibited a significant negative relationship between LE8 and PhenoAgeAccel in both male and female participants, with trend tests demonstrating significant results (p < 0.001 for males and p = 0.001 for females). (3) Restricted cubic spline (RCS) plots elucidated no significant non-linear trends between LE8 and PhenoAgeAccel overall and in gender subgroups (p for non-linear > 0.05). (4) Interaction effect tests denoted no interaction effects between the studied stratified variables such as age, gender, race, education level, and marital status on the relationship between LE8 and PhenoAgeAccel (p for interaction > 0.05). However, body mass index and diabetes manifested interaction effects (p for interaction < 0.05), suggesting that the influence of LE8 on PhenoAgeAccel might vary depending on an individual's BMI and diabetes status. Conclusion: This study, based on NHANES data from 2007-2010, has revealed a significant negative correlation between LE8 and PhenoAgeAccel, emphasizing the importance of maintaining a healthy lifestyle in slowing down the biological aging process. Despite the limitations posed by the study's design and geographical constraints, these findings provide a scientific basis for the development of public health policies focused on healthy lifestyle practices. Future research should further investigate the causal mechanisms underlying the relationship between LE8 and PhenoAgeAccel and consider cross-cultural comparisons to enhance our understanding of healthy aging.

Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints included the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) is associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Visual Intelligence Education as a Tool for Enhancing Medical Students' Self-Perception of Communication Skills.

Objective: Visual arts-based exposure and training are effective tools to enhance medical education. The visual arts can increase emotional intelligence and critical thinking skills. This study, conducted at Georgetown University School of Medicine (GUSoM) and the National Gallery of Art (NGA) in Washington, DC, was designed to measure the effect of a visual arts elective course on medical students' self-perception of their communication skills. Methods: This 6-week course involved lessons at the NGA and GUSoM for16 second-year medical students. The intervention students were age and gender-matched to14 second-year medical student control participants who took different elective courses. Prior to and following the intervention, the participants completed the Communication Skills Attitude Scale (CSAS). Statistical analysis was performed with either the 2-sided t-test or 2-sided Wilcoxon rank-sum test. Results: There were no statistically significant differences in the presurvey scores between the groups. However, there were 6 CSAS questions in the postsurveys that had statistically significant differences between the 2 groups. Within each group, there were also numerous statistically significant differences between their presurvey and postsurvey responses, with positive changes occurring in the intervention group (IG) and primarily negative changes occurring in the control group (CG). The NGA course improved the self-perception of communication skills, with students reporting stronger views on the importance of communication skills in teamwork and patient rapport. The CG, on the other hand, did not have as many improved perceptions of communication skills and had stronger opinions regarding not needing the ability to communicate well to be a good physician. Conclusion: This study indicates that medical student communication skills can benefit from exposure to visual arts activities and experiences. Future physicians must become effective communicators, and this study paves the way for research investigating the relationship between visual arts education and the development of a physician's communication skills.

Association between dietary and behavioral-based oxidative balance score and phenotypic age acceleration: a cross-sectional study of Americans.

OBJECTIVES: In light of the rise in the global aging population, this study investigated the potential of the oxidative balance score (OBS) as an indicator of phenotypic age acceleration (PhenoAgeAccel) to better understand and potentially slow down aging. METHODS: Utilizing data from the National Health and Nutrition Examination Survey collected between 2001 and 2010, including 13,142 United States adults (48.7% female and 51.2% male) aged 20 and above, OBS and PhenoAgeAccel were calculated. Weighted generalized linear regression models were employed to explore the associations between OBS and PhenoAgeAccel, including a sex-specific analysis. RESULTS: The OBS demonstrated significant variability across various demographic and health-related factors. There was a clear negative correlation observed between the higher OBS quartiles and PhenoAgeAccel, which presented sex-specific. RESULTS: the negative association between OBS and PhenoAgeAccel was more pronounced in male than in female. An analysis using restricted cubic splines revealed no significant non-linear relationships. Interaction effects were noted solely in the context of sex and hyperlipidemia. CONCLUSIONS: A higher OBS was significantly associated with a slower aging process, as measured by lower PhenoAgeAccel. These findings underscore the importance of OBS as a biomarker in the study of aging and point to sex and hyperlipidemia as variables that may affect this association. Additional research is required to confirm these results and to investigate the biological underpinnings of this relationship.

Evaluation of the Mechanism of Yishan Formula in Treating Breast Cancer Based on Network Pharmacology and Experimental Verification.

BACKGROUND: Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown. OBJECTIVE: In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments. METHODS: Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes. RESULTS: Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (AKT1, TP53, TNF, IL6, EGFR, SRC, VEGFA, STAT3, MAPK3, and JUN) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes. CONCLUSION: This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.

Neddylation in the chronically hypoperfused corpus callosum: MLN4924 reduces blood-brain barrier injury via ERK5/KLF2 signaling.

Blood-brain barrier (BBB) breakdown and cerebrovascular dysfunction may contribute to the pathology in white matter lesions and consequent cognitive decline caused by cerebral hypoperfusion. Neddylation is the process of attaching a ubiquitin-like molecule NEDD8 (neuronal precursor cell-expressed developmentally downregulated protein 8) to specific targets. By modifying protein substrates, neddylation plays critical roles in various important biological processes. However, whether neddylation influences the pathogenesis of hypoperfused brain remains unclear. In the present study, cerebral hypoperfusion-induced white matter lesions were produced by bilateral common carotid artery stenosis in mice. The function of the neddylation pathway, BBB integrity, cerebrovascular dysfunction, myelin density in the corpus callosum and cognitive function were determined. We show that NEDD8 conjugation aberrantly amplified in microvascular endothelium in the corpus callosum following cerebral hypoperfusion. MLN4924, a small-molecule inhibitor of NEDD8-activating enzyme currently in clinical trials, preserved BBB integrity, attenuated glial activation and enhanced oligodendrocyte differentiation, and reduced hypoperfusion-induced white matter lesions in the corpus callosum and thus improved cognitive performance via inactivating cullin-RING E3 ligase (CRL). Administration of MLN4924 caused the accumulation of ERK5 and KLF2. The ERK5 inhibitor BIX 02189, down-regulated MLN4924-induced activation of KLF2 and reversed MLN4924-mediated increase in pericyte coverage and junctional proteins. Furthermore, BIX 02189 blocked MLN4924-afforded protection against BBB disruption and white matter lesions in the corpus callosum. Collectively, our results revealed that neddylation impairs vascular function and thus exacerbated the pathology of hypoperfused brain and that inhibition of neddylation with MLN4924 may offer novel therapeutic opportunities for cerebral hypoperfusion-associated cognitive impairment.

Adjuvant nivolumab, capecitabine or the combination in patients with residual triple-negative breast cancer: the OXEL randomized phase II study.

Chemotherapy and immune checkpoint inhibitors have a role in the post-neoadjuvant setting in patients with triple-negative breast cancer (TNBC). However, the effects of nivolumab, a checkpoint inhibitor, capecitabine, or the combination in changing peripheral immunoscore (PIS) remains unclear. This open-label randomized phase II OXEL study (NCT03487666) aimed to assess the immunologic effects of nivolumab, capecitabine, or the combination in terms of the change in PIS (primary endpoint). Secondary endpoints include the presence of ctDNA, toxicity, clinical outcomes at 2-years and association of ctDNA and PIS with clinical outcomes. Forty-five women with TNBC and residual invasive disease after standard neoadjuvant chemotherapy were randomized to nivolumab, capecitabine, or the combination. Here we show that a combination of nivolumab plus capecitabine leads to a greater increase in PIS from baseline to week 6 (91%) compared with nivolumab (47%) or capecitabine (53%) alone (log-rank p = 0.08), meeting the pre-specified primary endpoint. In addition, the presence of circulating tumor DNA (ctDNA) was associated with disease recurrence, with no new safety signals in the combination arm. Our results provide efficacy and safety data on this combination in TNBC and support further development of PIS and ctDNA analyses to identify patients at high risk of recurrence.

Brachial-ankle pulse wave velocity increasing with heart rate accelerates.

Pulse wave velocity (PWV) indicates the degree of vascular stiffness. This study aimed to explore the association between heart rate (HR) and brachial-ankle (ba)-PWV in patients with pacemaker implantation. This retrospective observational study included patients who underwent permanent pacemaker implantation at the Second Hospital of Hebei Medical University between December 2018 and December 2021. All patients were pacemaker-dependent, and the ba-PWV values were collected during HR setted from 60 to 100 bpm. A total of 68 patients (34 males, aged 65.97 ± 9.90 years) were included in this study. There were significant difference of ba-PWV and diastolic blood pressure (DBP) among different HR (both P < 0.001). After adjusted systolic blood pressure (SBP), DBP, age, and sex, the generalized estimating equation showed ba-PWV was independently associated with HR, with increased HR showed higher coefficient: 70 bpm: ß = 42.26 (95% CI: 15.34-69.18, P = 0.002), 80 bpm: ß = 84.16 (95% CI: 52.48-115.84, P < 0.001), 90 bpm: ß = 129.27 (95% CI: 52.48-115.84, P < 0.001), and 100 bpm: 186.31 (95% CI: 137.02-235.59, P < 0.001). The results demonstrate that changes in HR may affect the ba-PWV, the ba-PWV values tend to be higher when HR accelerates.

Poly(ethylene glycol) Hydrogels with the Sustained Release of Hepatocyte Growth Factor for Enhancing Vascular Regeneration.

The surface modification of biologically active factors on tissue-engineering vascular scaffold fails to fulfill the mechanical property and bioactive compounds' sustained release in vivo and results in the inhibition of tissue regeneration of small-diameter vascular grafts in vascular replacement therapies. In this study, biodegradable poly(ε-caprolactone) (PCL) was applied for scaffold preparation, and poly(ethylene glycol) (PG) hydrogel was used to load heparin and hepatocyte growth factor (HGF). In vitro analysis demonstrated that the PCL scaffold could inhibit the heparin release from the PG hydrogel, and the PG hydrogel could inhibit heparin release during the process of PCL degradation. Finally, it results in sustained release of HGF and heparin from the PCL-PG-HGF scaffold. The mechanical property of this hybrid scaffold improved after being coated with the PG hydrogel. In addition, the PCL-PG-HGF scaffold illustrated no inflammatory lesions, organ damage, or biological toxicity in all primary organs, with rapid organization of the endothelial cell layer, smooth muscle regeneration, and extracellular matrix formation. These results indicated that the PCL-PG-HGF scaffold is biocompatible and provides a microenvironment in which a tissue-engineered vascular graft with anticoagulant properties allows regeneration of vascular tissue (Scheme 1). Such findings confirm the feasibility of creating hydrogel scaffolds coated with bioactive factors to prepare novel vascular grafts.

Efficacy of Electronic Reminders in Increasing the Enhanced Recovery After Surgery Protocol Use During Major Breast Surgery: Prospective Cohort Study.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are patient-centered, evidence-based guidelines for peri-, intra-, and postoperative management of surgical candidates that aim to decrease operative complications and facilitate recovery after surgery. Anesthesia providers can use these protocols to guide decision-making and standardize aspects of their anesthetic plan in the operating room. OBJECTIVE: Research across multiple disciplines has demonstrated that clinical decision support systems have the potential to improve protocol adherence by reminding providers about departmental policies and protocols via notifications. There remains a gap in the literature about whether clinical decision support systems can improve patient outcomes by improving anesthesia providers' adherence to protocols. Our hypothesis is that the implementation of an electronic notification system to anesthesia providers the day prior to scheduled breast surgeries will increase the use of the already existing but underused ERAS protocols. METHODS: This was a single-center prospective cohort study conducted between October 2017 and August 2018 at an urban academic medical center. After obtaining approval from the institutional review board, anesthesia providers assigned to major breast surgery cases were identified. Patient data were collected pre- and postimplementation of an electronic notification system that sent the anesthesia providers an email reminder of the ERAS breast protocol the night before scheduled surgeries. Each patient's record was then reviewed to assess the frequency of adherence to the various ERAS protocol elements. RESULTS: Implementation of an electronic notification significantly improved overall protocol adherence and several preoperative markers of ERAS protocol adherence. Protocol adherence increased from 16% (n=14) to 44% (n=44; P<.001), preoperative administration of oral gabapentin (600 mg) increased from 13% (n=11) to 43% (n=43; P<.001), and oral celebrex (400 mg) use increased from 16% (n=14) to 35% (n=35; P=.006). There were no statistically significant differences in the use of scopolamine transdermal patch (P=.05), ketamine (P=.35), and oral acetaminophen (P=.31) between the groups. Secondary outcomes such as intraoperative and postoperative morphine equivalent administered, postanesthesia care unit length of stay, postoperative pain scores, and incidence of postoperative nausea and vomiting did not show statistical significance. CONCLUSIONS: This study examines whether sending automated notifications to anesthesia providers increases the use of ERAS protocols in a single academic medical center. Our analysis exhibited statistically significant increases in overall protocol adherence but failed to show significant differences in secondary outcome measures. Despite the lack of a statistically significant difference in secondary postoperative outcomes, our analysis contributes to the limited literature on the relationship between using push notifications and clinical decision support in guiding perioperative decision-making. A variety of techniques can be implemented, including technological solutions such as automated notifications to providers, to improve awareness and adherence to ERAS protocols.

Integrin beta 3-overexpressing mesenchymal stromal cells display enhanced homing and can reduce atherosclerotic plaque.

BACKGROUND: Umbilical cord (UC) mesenchymal stem cell (MSC) transplantation is a potential therapeutic intervention for atherosclerotic vascular disease. Integrin beta 3 (ITGB3) promotes cell migration in several cell types. However, whether ITGB-modified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear. AIM: To investigate whether ITGB3-overexpressing MSCs (MSCsITGB3) would exhibit improved homing efficacy in atherosclerosis. METHODS: UC MSCs were isolated and expanded. Lentiviral vectors encoding ITGB3 or green fluorescent protein (GFP) as control were transfected into MSCs. Sixty male apolipoprotein E-/- mice were acquired from Beijing Vital River Lab Animal Technology Co., Ltd and fed with a high-fat diet (HFD) for 12 wk to induce the formation of atherosclerotic lesions. These HFD-fed mice were randomly separated into three clusters. GFP-labeled MSCs (MSCsGFP) or MSCsITGB3 were transplanted into the mice intravenously via the tail vein. Immunofluorescence staining, Oil red O staining, histological analyses, western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction were used for the analyses. RESULTS: ITGB3 modified MSCs successfully differentiated into the "osteocyte" and "adipocyte" phenotypes and were characterized by positive expression (> 91.3%) of CD29, CD73, and CD105 and negative expression (< 1.35%) of CD34 and Human Leukocyte Antigen-DR. In a transwell assay, MSCsITGB3 showed significantly faster migration than MSCsGFP. ITGB3 overexpression had no effects on MSC viability, differentiation, and secretion. Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites. Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCsITGB3, significantly reducing the plaque area. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSCITGB3 transplantation considerably decreased the inflammatory response in pathological tissues by improving the dynamic equilibrium of pro- and anti-inflammatory cytokines. CONCLUSION: These results showed that ITGB3 overexpression enhanced the MSC homing ability, providing a potential approach for MSC delivery to plaque sites, thereby optimizing their therapeutic effects.

Water Intake and Handgrip Strength in US Adults: A Cross-Sectional Study Based on NHANES 2011-2014 Data.

This study aimed to examine the relationship between daily total intake of water (DTIW) and handgrip strength (HGS) among US adults and to explore the impact of water intake on muscle function and health, providing a reference for public health policies and health education. Using the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, a cross-sectional survey design was adopted to analyze 5427 adults (48.37% female and 51.63% male) aged 20 years and above. DTIW was assessed using two non-consecutive 24 h dietary recall interviews, and the HGS level was measured using a Takei Dynamometer. Weighted generalized linear regression models and restricted cubic spline plots were used to analyze the linear and nonlinear associations between DTIW and HGS level and to conduct a gender subgroup analysis and an interaction effect test. The results showed that there were significant differences in HGS and other characteristics among different quartile groups of DTIW (p < 0.05). There was a significant nonlinear trend (exhibiting an inverted U-curve) between DTIW and HGS (p for nonlinear = 0.0044), with a cut-off point of 2663 g/day. Gender subgroup analysis showed that the nonlinear trend (exhibiting an inverted U-curve) was significant only in males (p for nonlinear = 0.0016), with a cut-off point of 2595 g/day. None of the stratified variables had an interaction effect on the association between DTIW and HGS (p for interaction > 0.05). In conclusion, this study found a nonlinear association between DTIW and HGS levels, as well as a gender difference. This finding provides new clues and directions for exploring the mechanism of the impact of DTIW on muscle function and health and also provides new evidence and suggestions for adults to adjust their water intake reasonably.

Risk Factors for Stroke Development After Thoracic Aortic Surgery.

OBJECTIVES: Stroke after thoracic aortic surgery is a complication that is associated with poor outcomes. The aim is to characterize the intraoperative risk factors for stroke development. DESIGN: A retrospective analysis. SETTING: Tertiary, high-volume cardiac surgery center. PARTICIPANTS: Patients who had surgical repair of thoracic aortic diseases from January 1, 2017, through December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 704 patients were included, of whom 533 had ascending aortic aneurysms, and 171 had type A aortic dissection. The incidence of postoperative stroke was 4.5% (95% CI 2.9%-6.6%) for ascending aortic aneurysms compared with 12.3% (95% CI 7.8%-18.16%) in type-A aortic dissections. Patients who developed postoperative strokes had significantly lower intraoperative hemoglobin median (7.5 gm/dL [IQR 6.8-8.6] v 8.55 gm/dL [IQR 7.3-10.0]; p < 0.001). The median cardiopulmonary bypass time was 185 minutes (IQR 136-328) in the stroke group versus 156 minutes (IQR 113-206) in the nonstroke group (p = 0.014). Circulatory arrest was used in 57.8% versus 38.5% of the nonstroke patients (p = 0.017). The initial temperature after leaving the operating room was lower, with a median of 35.0°C (IQR 34-35.92) in the stroke group versus 35.5°C (IQR 35-36) in the nonstroke cohort (p = 0.021). CONCLUSIONS: This single-center study highlighted the potential importance of intra-operative factors in preventing stroke. Lower hemoglobin, longer duration of cardiopulmonary bypass, deep hypothermic circulatory arrest, and postoperative hypothermia are potential risk factors for postoperative stroke. Further studies are needed to prevent this significant complication in patients with thoracic aortic diseases.