Ileal Paneth Cell Phenotype is a Cellular Biomarker for Pouch Complications in Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers that integrate genetic and environmental factors and predict outcome in complex immune diseases such as inflammatory bowel disease (IBD; including Crohn's disease [CD] and ulcerative colitis [UC]) are needed. We showed that morphologic patterns of ileal Paneth cells (Paneth cell phenotype [PCP]; a surrogate for PC function) is one such cellular biomarker for CD. Given the shared features between CD and UC, we hypothesized that PCP is also associated with molecular/genetic features and outcome in UC. Because PC density is highest in the ileum, we further hypothesized that PCP predicts outcome in UC subjects who underwent total colectomy and ileal pouch-anal anastomosis (IPAA). METHODS: Uninflamed ileal resection margins from UC subjects with colectomy and IPAA were used for PCP and transcriptomic analyses. PCP was defined using defensin 5 immunofluorescence. Genotyping was performed using Immunochip. UC transcriptomic and genotype associations of PCP were incorporated with data from CD subjects to identify common IBD-related pathways and genes that regulate PCP. RESULTS: The prevalence of abnormal ileal PCP was 27%, comparable to that seen in CD. Combined analysis of UC and CD subjects showed that abnormal PCP was associated with transcriptomic pathways of secretory granule maturation and polymorphisms in innate immunity genes. Abnormal ileal PCP at the time of colectomy was also associated with pouch complications including de novo CD in the pouch and time to first episode of pouchitis. CONCLUSIONS: Ileal PCP is biologically and clinically relevant in UC and can be used as a biomarker in IBD.

Intracoronary Versus Intravenous Low-Dose Tirofiban in Patients With ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: This meta-analysis aimed to evaluate the effects of intracoronary (IC) low-dose tirofiban versus intravenous (IV) administration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: All published randomised controlled trials (RCTs) comparing the effects of IC low-dose tirofiban (a bolus of ≤10 ug/kg) versus IV administration in patients with STEMI were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from inception to June 2023, with no language restriction. The risk ratio (RR) with 95% confidence intervals (CI) and the weighted mean difference (WMD) with 95% CI were calculated. RESULTS: Eleven RCTs involving 1,802 patients were included. Compared with the IV group, IC low-dose tirofiban was associated with improved major adverse cardiac events rate (RR 0.595, 95% CI 0.442-0.802; p=0.001), left ventricular ejection fraction (WMD 1.982, 95% CI 0.565-3.398; p=0.006), thrombolysis in myocardial infarction (TIMI) flow grade (RR 1.065, 95% CI 1.004-1.131; p=0.037), and TIMI myocardial perfusion grade (RR 1.194, 95% CI 1.001-1.425; p=0.049). The two groups had no significant difference in bleeding events (RR 0.952, 95% CI 0.709-1.279; p=0.745). CONCLUSIONS: Intracoronary low-dose tirofiban administration may be a safe and effective alternative to IV administration in STEMI patients.

A nomogram for predicting neurogenic lower urinary tract dysfunction in patients with acute ischemic stroke: A retrospective study.

AIMS: To investigate the risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS), and develop an internally validated predictive nomogram. The study aims to offer insights for preventing AIS-NLUTD. METHODS: We conducted a retrospective study on AIS patients in a Shenzhen Hospital from June 2021 to February 2023, categorizing them into non-NLUTD and NLUTD groups. The bivariate analysis identified factors for AIS-NLUTD (p < 0.05), integrated into a least absolute shrinkage and selection operator (LASSO) regression model. Significant variables from LASSO were used in a multivariate logistic regression for the predictive model, resulting in a nomogram. Nomogram performance and clinical utility were evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). Internal validation used 1000 bootstrap resamplings. RESULTS: A total of 373 participants were included in this study, with an NLUTD incidence rate of 17.7% (66/373). NIHSS score (OR = 1.254), pneumonia (OR = 6.631), GLU (OR = 1.240), HGB (OR = 0.970), and hCRP (OR = 1.021) were used to construct a predictive model for NLUTD in AIS patients. The model exhibited good performance (AUC = 0.899, calibration curve p = 0.953). Internal validation of the model demonstrated strong discrimination and calibration abilities (AUC = 0.898). Results from DCA and CIC curves indicated that the prediction model had high clinical utility. CONCLUSIONS: We developed a predictive model for AIS-NLUTD and created a nomogram with strong predictive capabilities, assisting healthcare professionals in evaluating NLUTD risk among AIS patients and facilitating early intervention.

Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart against ischemia/reperfusion injury by limiting TNFα-induced mitochondrial injury in experimental diabetes.

AIMS: The histone deacetylase 6 (HDAC6) inhibitor, tubastatin A, reduces myocardial ischemia/reperfusion injury (MIRI) in type 1 diabetic rats. It remains unclear whether HDAC6 regulates MIRI in type 2 diabetic animals. Diabetes augments activity of HDAC6 and generation of tumor necrosis factor α (TNFα) and impairs mitochondrial complex I (mCI). Here we examined how HDAC6 regulates TNFα production, mCI activity, mitochondria, and cardiac function in type 1 and type 2 diabetic mice undergoing MIRI. METHODS AND RESULTS: HDAC6 knockout, streptozotocin-induced type 1 diabetic, and obese type 2 diabetic db/db mice underwent MIRI in vivo or ex vivo in a Langendorff-perfused system. We found that MIRI and diabetes additively augmented myocardial HDAC6 activity and generation of TNFα, along with cardiac mitochondrial fission, low bioactivity of mCI, and low production of ATP. Importantly, genetic disruption of HDAC6 or tubastatin A decreased TNFα levels, mitochondrial fission, and myocardial mitochondrial NADH levels in ischemic/reperfused diabetic mice, concomitant with augmented mCI activity, decreased infarct size, and improved cardiac function. Moreover, HDAC6 knockout or tubastatin A treatment decreased left ventricular dilation and improved cardiac systolic function 28 days after MIRI. H9c2 cardiomyocytes with and without HDAC6 knockdown were subjected to hypoxia/reoxygenation injury in the presence of high glucose. Hypoxia/reoxygenation augmented HDAC6 activity and TNFα levels and decreased mCI activity. These negative effects were blocked by HDAC6 knockdown. CONCLUSIONS: HDAC6 is an essential negative regulator of MIRI in diabetes. Genetic deletion or pharmacologic inhibition of HDAC6 protects the heart from MIRI by limiting TNFα-induced mitochondrial injury in experimental diabetes.

Comparable cerebral cortex activity and gait performance in elderly hypertensive and healthy individuals during dual-task walking: A fNIRS study.

BACKGROUND: Hypertension increases the risk of cognitive impairment and related dementia, causing impaired executive function and unusual gait parameters. However, the mechanism of neural function illustrating this is unclear. Our research aimed to explore the differences of cerebral cortex activation, gait parameters, and working memory performance between healthy older adults (HA) and older hypertensive (HT) patients when performing cognitive and walking tasks. METHOD: A total of 36 subjects, including 12 healthy older adults and 24 older hypertensive patients were asked to perform series conditions including single cognitive task (SC), single walking task (SW), and dual-task (DT), wearing functional near-infrared spectroscopy (fNIRS) equipment and Intelligent Device for Energy Expenditure and Activity equipment to record cortical hemodynamic reactions and various gait parameters. RESULTS: The left somatosensory cortex (L-S1) and bilateral supplementary motor area (SMA) showed higher cortical activation (p < .05) than HA when HT performed DT. The intragroup comparison showed that HT had higher cortical activation (p < .05) when performing DT as SW. The cognitive performance of HT was significantly worse (p < .05) than HA when executing SC. The activation of the L-S1, L-M1, and bilateral SMA in HT were significantly higher during SW (p < .05). CONCLUSION: Hypertension can lead to cognitive impairment in the elderly, including executive function and walking function decline. As a result of these functional declines, elderly patients with hypertension are unable to efficiently allocate brain resources to support more difficult cognitive interference tasks and need to meet more complex task demands by activating more brain regions.

Changes in the microbial community of semen exposed to different simulated forensic situations.

Semen is one of the common body fluids in sexual crime cases. The current methods of semen identification have certain limitations, so it is necessary to search for other methods. In addition, there are few reports of microbiome changes in body fluids under simulated crime scenes. It is essential to further reveal the changes in semen microbiomes after exposure to various simulated crime scenes. Semen samples from eight volunteers were exposed in closed plastic bags, soil, indoor, cotton, polyester, and wool fabrics. A total of 68 samples (before and after exposure) were collected, detected by 16S rDNA sequencing, and analyzed for the microbiome signature. Finally, a random forest model was constructed for body fluid identification. After exposure, the relative abundance of Pseudomonas and Rhodococcus changed dramatically in almost all groups. In addition, the treatment with the closed plastic bags or soil groups had a greater impact on the semen microbiome. According to the Shannon indices, the alpha diversity of the closed plastic bags and soil groups was much lower than that of the other groups. Attention should be given to the above two scenes in practical work of forensic medicine. In this study, the accuracy of semen recognition was 100%. The exposed semen can still be correctly identified as semen based on its microbiota characteristics. In summary, semen microbiomes exposed to simulated crime scenes still have good application potential for body fluid identification. IMPORTANCE: In this study, the microbiome changes of semen exposed to different environments were observed, and the exposed semen microbiome still has a good application potential in body fluid identification.

Exploring the pharmacological mechanisms of the flower of Rhododendron molle in rheumatoid arthritis rats based on metabolomics integrated network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine, the flower of Rhododendron molle G. Don (RMF) is record in the Chinese pharmacopoeia, and is commonly utilized for treating rheumatoid arthritis (RA) in clinical practice. However, its precise mechanisms necessitate further exploration. AIM OF THE STUDY: To expound the effective components, targets, metabolites, and pathways participated in RMF's anti-RA effects by metabolomics integrated network pharmacology. MATERIALS AND METHODS: CIA rats were intragastric administered RMF for 2 weeks, following which the therapeutic effects were comprehensively evaluated. Serum metabolomics was adopted to investigate the differential metabolites (DEMs). UHPLC-Q-Exactive-MS method was applied to identify the components of RMF, and then network pharmacology was utilize to select the component-RA-targets. Molecular docking and Western blotting were utilized to validate the key targets. RESULTS: RA symptoms were alleviated by RMF through the inhibition secretion of pro-inflammatory factors IL-1ß, IL-6 and TNF-α, along with relief in bone destruction observed in CIA rats. Four targets, namely AKR1B1, TPH1, CYP1A1, and CYP1A2, were identified, along with their corresponding metabolites, namely D-glucose, D-mannose, L-tryptophan, 11-deoxycorticosterone, and 17α-hydroxyprogesterone. These were found to be involved in three key metabolic pathways: steroid hormone biosynthesis, tryptophan metabolism, and galactose metabolism. Additionally, five significant anti-RA active components were identified from RMF, including Rhodojaponin (Rj)-Ⅱ, Rj-Ⅲ, Rj-Ⅴ, Rj-Ⅵ, and quercetin. CONCLUSIONS: The anti-RA mechanisms of RMF were investigated in this study, focusing on active components, upstream targets, and downstream metabolites. These findings lay a foundation for the clinical practice and drug development of RMF.

CRISPR-array-mediated imaging of non-repetitive and multiplex genomic loci in living cells.

Dynamic imaging of genomic loci is key for understanding gene regulation, but methods for imaging genomes, in particular non-repetitive DNAs, are limited. We developed CRISPRdelight, a DNA-labeling system based on endonuclease-deficient CRISPR-Cas12a (dCas12a), with an engineered CRISPR array to track DNA location and motion. CRISPRdelight enables robust imaging of all examined 12 non-repetitive genomic loci in different cell lines. We revealed the confined movement of the CCAT1 locus (chr8q24) at the nuclear periphery for repressed expression and active motion in the interior nucleus for transcription. We uncovered the selective repositioning of HSP gene loci to nuclear speckles, including a remarkable relocation of HSPH1 (chr13q12) for elevated transcription during stresses. Combining CRISPR-dCas12a and RNA aptamers allowed multiplex imaging of four types of satellite DNA loci with a single array, revealing their spatial proximity to the nucleolus-associated domain. CRISPRdelight is a user-friendly and robust system for imaging and tracking genomic dynamics and regulation.

Integrative Analysis of Lactylome and Proteome of Hypertrophic Scar To Identify Pathways or Proteins Associated with Disease Development.

Lactylation (Kla), a recently discovered post-translational modification derived from lactate, plays crucial roles in various cellular processes. However, the specific influence of lactylation on the biological processes underlying hypertrophic scar formation remains unclear. In this study, we present a comprehensive profiling of the lactylome and proteome in both hypertrophic scars and adjacent normal skin tissues. A total of 1023 Kla sites originating from 338 nonhistone proteins were identified based on lactylome analysis. Proteome analysis in hypertrophic scar and adjacent skin samples revealed the identification of 2008 proteins. It is worth noting that Kla exhibits a preference for genes associated with ribosome function as well as glycolysis/gluconeogenesis in both normal skin and hypertrophic scar tissues. Furthermore, the functional enrichment analysis demonstrated that differentially lactyled proteins are primarily involved in proteoglycans, HIF-1, and AMPK signaling pathways. The combined analysis of the lactylome and proteome data highlighted a significant upregulation of 14 lactylation sites in hypertrophic scar tissues. Overall, our investigation unveiled the significant involvement of protein lactylation in the regulation of ribosome function as well as glycolysis/gluconeogenesis, potentially contributing to the formation of hypertrophic scars.

The relationship between social and psychological factors with cognitive impairment after stroke: a prospective study.

Objectives: To investigate the association between social and psychological factors and the risk of cognitive impairment following acute ischemic stroke. Materials and methods: A prospective study was conducted at Shanghai Tenth People's Hospital from June 2021 to July 2022. The study focused on social and psychological factors, which were assessed using the Social Support Rating Scale (SSRS), Self-Perceived Burden Scale (SPBS), and Hamilton Depression Scale (HAMD) within 3 days after admission to the hospital. Cognitive function was evaluated using the Montreal Cognitive Assessment at 3 months post-stroke. Logistic hierarchical regression models were used to examine the association between these three indicators and cognitive impairment following a stroke. Results: Among these patients, cognitive function was assessed in 211 cases at the 3-month follow-up after the initial stroke event. At 3 months post-stroke, 118(55.9%) of the participants experienced cognitive impairment, while 93(44.1%) did not. The scores on the SPBS and HAMD showed significant associations with cognitive impairment at 3 months after stroke. The scores of SPBS [scores: 30~39 vs.<20 points, odds ratio (OR)=2.993 (1.135-7.896); scores: ≥40 vs.<20points, OR=7.382 (1.117-48.799); P=0.043] and the HAMD [scores: >7 vs.≤7 points, OR=3.287(1.362~7.936); P=0.008]. There were no significant associations observed between SSRS and PSCI. Conclusion: Early screening for depressive symptoms and focusing on self-perceived burden can be beneficial for decision support for clinicians and improve cognitive function recovery at the 3-month mark post-stroke.

Epidemiologic trends and changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae infection during 2019-2023.

PURPOSE: To understand the changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae (MP) infection from 2019 to 2023. METHODS: This study retrospectively analyzed inpatients aged 0-14 years who were diagnosed with MP infection or MP pneumonia in a tertiary hospital from January 2019 to December 2023. The children were divided into three groups: before the implementation of nonpharmaceutical interventions (NPIs), during the implementation of NPIs, and after the NPIs being lifted. RESULTS: A total of 4103 patients were enrolled in this study, of whom 2125 were diagnosed with MP infection and 1978 were diagnosed with MP pneumonia. The number of MP infection cases dramatically decreased early during the implementation of NPIs, and the previous epidemic trend resumed after the NPIs were lifted, with the number of cases during the period 2019-2023 peaked in November 2023. In children aged < 5 years, the levels of IgA and IgM and the percentages of total T cells and cytotoxic T cells in the "before the implementation of NPIs" group were greater than those in the other groups, and the percentage of total B cells was lower than that in the other groups. In children aged ≥ 5 years, the IgM level in the "before the implementation of NPIs" group was greater than that in the other groups. CONCLUSION: The number of MP-infected hospitalized children decreased significantly after NPI implementation and reached its highest peak during 2019-2023 in November 2023. After the NPIs were lifted, the level of humoral immunity was decreased and balance lymphocyte subsets were disrupted, especially in children aged < 5 years. We should pay close attention to and prevent MP infection in a timely manner after epidemics caused by large respiratory pathogens.

Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients.

Background: Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model. Methods: Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results: The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P<0.01). Moreover, the levels of PD1+ NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1+ NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1+ NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; P<0.001). Conclusion: The study provides novel insights into the association between PD1+NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.

Amide proton transfer-weighted and arterial spin labeling imaging may improve differentiation between high-grade glioma recurrence and radiation-induced brain injury.

Rationale and objectives: The management of tumor recurrence (TR) and radiation-induced brain injury (RIBI) poses significant challenges, necessitating the development of effective differentiation strategies. In this study, we investigated the potential of amide proton transfer-weighted (APTw) and arterial spin labeling (ASL) imaging for discriminating between TR and RIBI in patients with high-grade glioma (HGG). Methods: A total of 64 HGG patients receiving standard treatment were enrolled in this study. The patients were categorized based on secondary pathology or MRI follow-up results, and the demographic characteristics of each group were presented. The APTw, rAPTw, cerebral blood flow (CBF) and rCBF values were quantified. The differences in various parameters between TR and RIBI were assessed using the independent-samples t-test. The discriminative performance of these MRI parameters in distinguishing between the two conditions was assessed using receiver operating characteristic (ROC) curve analysis. Additionally, the Delong test was employed to further evaluate their discriminatory ability. Results: The APTw and CBF values of TR were significantly higher compared to RIBI (P < 0.05). APTw MRI demonstrated superior diagnostic efficiency in distinguishing TR from RIBI (area under the curve [AUC]: 0.864; sensitivity: 75.0 %; specificity: 81.8 %) when compared to ASL imaging. The combined utilization of APTw and CBF value further enhanced the AUC to 0.922. The Delong test demonstrated that the combination of APTw and ASL exhibited superior performance in the identification of TR and RIBI, compared to ASL alone (P = 0.048). Conclusion: APTw exhibited superior diagnostic efficacy compared to ASL in the evaluation of TR and RIBI. Furthermore, the combination of APTw and ASL exhibits greater discriminatory capability and diagnostic performance.

Bibliometric analysis of research in epilepsy and comorbid depression from 2014 to 2023.

BACKGROUND: Epilepsy and depression have complicated bidirectional relationships. Our study aimed to explore the field of epilepsy comorbid with depression in a bibliometric perspective from 2014-2023. AIM: To improve our understanding of epilepsy and depression by evaluating the relationship between epilepsy and depression, bibliometric analyses were performed. METHODS: Epilepsy and depression-related publications from the last decade were retrieved from the Web of Science Core Collection. We conducted bibliometric and visual analysis using VOSviewer and CiteSpace, examining authorships, countries, institutions, journals of publication, co-citations of references, connections between keywords, clusters of keywords, and keywords with citation bursts. RESULTS: Over the past ten years, we collected 1045 research papers focusing on the field of epilepsy and comorbid depression. Publications on epilepsy and depression have shown a general upward trend over time, though with some fluctuations. The United States, with 287 articles, and the University of Melbourne, contributing 34 articles, were the top countries and institutions, respectively. In addition, in the field of epilepsy and depression, Professor Lee, who has published 30 articles, was the most contributing author. The hot topics pay attention to the quality of life in patients with epilepsy and depression. CONCLUSION: We reported that quality of life and stigma in patients with epilepsy comorbid with depression are possible future hot topics and directions in the field of epilepsy and depression research.

Identification of a prognostic DNA repair gene signature in esophageal cancer.

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

A retrospective study on the prevalence and risk factors of neurogenic lower urinary tract dysfunction for acute ischemic stroke in China: A case-control study.

PURPOSE: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. MATERIALS AND METHODS: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann-Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. RESULTS: Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. CONCLUSIONS: A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

Bibliometric and visual analysis of immunisation associated with acute kidney injury from 2003 to 2023.

Objective: This study aims to conduct a detailed bibliometric and visual analysis of acute kidney injury (AKI) and immune-related research conducted over the past two decades, focusing on identifying emerging trends and key areas of interest. Methods: The Web of Science Core Collection (WoSCC) was utilised for the meticulous examination of various parameters including publication volume, authorship, geographic distribution, institutional contributions, journal sources, prevalent keywords and citation frequencies. Data were intricately visualised and interpreted using VOSviewer, CiteSpace and Excel 365 software. Results: Analysis of the WoSCC database revealed 3,537 articles on AKI and immunisation, originating from 94 countries and regions, involving 3,552 institutions and authored by 18,243 individuals. Notably, the top five countries contributing to this field were the United States, China, Germany, Italy and the United Kingdom, with the United States leading with 35.76% of total publications. Among the 3,552 contributing institutions, those in the United States were predominant, with Harvard University leading with 134 papers and 3,906 citations. Key journals driving productivity included Frontiers in Immunology, Kidney International, Journal of the American Society of Nephrology and International Journal of Molecular Sciences, with Kidney International being the most cited, followed by Journal of the American Society of Nephrology and New England Journal of Medicine. Prominent authors in the field included Ronco Claudio, Okusa Mark D and Anders, Hans-Joachim. Co-citation clustering and timeline analysis highlighted recent research foci such as COVID-19, immune checkpoint inhibitors, regulated necrosis, cirrhosis and AKI. Keyword analysis identified "inflammation," "ischaemia-reperfusion injury," "sepsis," "covid-19," and "oxidative stress" as prevalent terms. Conclusion: This study provides the first bibliometric analysis of AKI and immune research, offering a comprehensive overview of research hotspots and evolving trends within the field.

Unified and distinct cognitive control deficits in adolescents with cognitive disengagement syndrome and learning burnout.

Introduction: Cognitive disengagement syndrome (CDS) is a psychological disorder characterized by daydreaming, mental fogginess, and slow thinking, while learning burnout (LB) is characterized by a passive and inattentive attitude toward learning. These two disorders are closely related but can be challenging to differentiate from one another. The present study aimed to identify shared and distinct cognitive control deficits between CDS and LB. Methods: We recruited 136 adolescents (aged 14 to 17 years) from an initial screening of CDS and LB (N = 476) and divided them into four groups: CDS, LB, CDS + LB, and typically developing control. After a second screening, 129 adolescents completed two tasks to assess their attentional networks and cognitive control capacity (CCC). Results: Adolescents with high CDS symptoms (both CDS group and CDS+LB group) exhibited impaired disengaging effect of attention and lower CCC, indicating deficits in orienting attention and the upper limit of information processing for cognitive control specifically. Furthermore, support vector machine modeling identified CCC as the most significant parameter differentiating the CDS and LB groups. Discussion: Our findings suggest that while adolescents with high CDS and high LB symptoms have similar outward manifestations in the adolescent's school life, deficits in attention and cognitive control, particularly in the CCC, may distinguish between the two groups.

Enhanced Tissue Regeneration Through Immunomodulatory Extracellular Vesicles Encapsulated in Diversified Silk-Based Injectable Hydrogels.

Mesenchymal stem cells (MSCs) immunologically trained using lipopolysaccharide (LPS) display enhanced immunomodulatory capabilities. Extracellular vesicles (EVs) derived from MSCs are widely used in regenerative medicine owing to their bioactive properties without the drawbacks of cell therapy. However, it remains unclear whether EVs derived from LPS-stimulated (trained) MSCs (L-EVs) inherit the enhanced reparative potential from their parent cells. Thus, this study first aims to explore the effect of immunological training on the bioactivity of L-EVs. LPS-trained bone marrow-derived MSCs (BMSCs) secrete more EVs, and these EVs significantly promote M2 macrophage polarization. Subsequently, hydrogel systems based on thixotropic injectable silk fibroin are prepared for in vivo EV delivery. These hydrogels have controllable gelation time and exhibit outstanding reparative effects on rat skin wounds and alveolar bone defects. Finally, it is revealed that L-EVs promote M2 macrophage polarization by inhibiting the nuclear translocation of PKM2. Overall, this study shows that the immunological training of BMSCs effectively improves the therapeutic effects of their EVs and provides a convenient and diversified EV delivery strategy using an injectable silk fibroin hydrogel. This strategy has broad clinical application prospects for tissue regeneration.