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1.
Front Cardiovasc Med ; 11: 1364332, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707890

RESUMEN

Background: Postoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies. Methods: This was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling. Results: A total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69-0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience. Conclusion: Our study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.

2.
Neuropsychiatr Dis Treat ; 20: 979-987, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38741580

RESUMEN

Background: Postoperative delirium (POD) significantly impacts patient outcomes after acute type A aortic dissection (ATAAD) surgeries. This study investigates the role of Neuronal Pentraxin 2 (NPTX2) as a potential biomarker for POD in ATAAD patients. Methods: This secondary analysis involved ATAAD patients from a prospective observational study. Serum NPTX2 levels were measured preoperatively and immediately postoperatively using Enzyme-Linked Immunosorbent Assay (ELISA). Delirium was assessed using the Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU). Statistical analyses included the Pearson Correlation Coefficient and multivariate logistic regression to evaluate the association between NPTX2 levels and POD. Results: Among the 62 patients included, 46.77% developed POD. Patients with POD had significantly lower preoperative and postoperative serum NPTX2 levels. The Receiver Operating Characteristic (ROC) curve analysis showed that postoperative NPTX2 had a strong predictive capability for POD (AUC = 0.895). The optimal cutoff for postoperative NPTX2 in predicting POD was less than 421.4 pg/mL. Preoperative NPTX2 also demonstrated predictive value, albeit weaker (AUC = 0.683). Conclusion: Serum NPTX2 levels, both preoperatively and postoperatively, are promising biomarkers for predicting POD in ATAAD patients. These findings suggest that NPTX2 could be instrumental in early POD detection and intervention strategies.

3.
Sci Rep ; 14(1): 7845, 2024 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570622

RESUMEN

Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002-1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250-5.475), hemopericardium (OR, 2.767; 95% CI, 1.150-7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001-1.014), RBP Delta (OR, 1.047; 95% CI, 1.020-1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794-0.907), and Beta (OR, 0.755; 95% CI, 0.649-0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011-1.032), RBP Delta (OR, 1.168; 95% CI, 1.105-1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135-1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p < 0.001), and hospital stays (p = 0.002). We obtained the simplest predictive model for TND, consisting of three variables (CPB time ≥ 180 min, RBP Delta, RBP Theta, upon which we constructed column charts. The areas under the receiver operating characteristic (AUROC) were 0.821 (0.755, 0.887). Our study demonstrates that postoperative RBP monitoring can detect changes in brain function in patients with TAAD during the perioperative period, providing clinicians with an effective predictive method that can help improve postoperative TND in TAAD patients. These findings have important implications for improving clinical care in this population.Trial registration ChiCTR2200055980. Registered 30th Jan. 2022. This trial was registered before the first participant was enrolled.


Asunto(s)
Disección Aórtica , Azidas , Desoxiglucosa/análogos & derivados , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Disección Aórtica/cirugía , Resultado del Tratamiento , Factores de Riesgo , Estudios Retrospectivos , Complicaciones Posoperatorias/etiología
4.
Trials ; 25(1): 250, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600561

RESUMEN

BACKGROUND: Acute type A aortic dissection (aTAAD) is a critical and life-threatening condition. Previous research has demonstrated that the use of ketorolac not only reduces the progression, incidence, and severity of aortic aneurysms in animal models, but also decreases postoperative mortality and complications in patients undergoing open abdominal aortic aneurysm replacement. However, there is a lack of studies investigating the efficacy of ketorolac in treating aTAAD in humans. Therefore, we conducted a study to evaluate the safety and efficacy of ketorolac in patients with aTAAD. Our hypothesis was that ketorolac treatment for aTAAD patients would meet safety indicators and effectively improve patient prognosis. METHODS/DESIGN: This study is a single-center, randomized, double-blinded, and placebo-controlled study. A total of 120 patients with aTAAD will be recruited and will be randomized into the ketorolac group and placebo group with a ratio of 1:1. Ketorolac tromethamine 60 mg per 2 ml will be intramuscularly injected within 2 h before surgery, followed by intramuscular injections of 30 mg per 1 ml BID. on the first and second postoperative days in the Ketorolac group, while 0.9% saline will be administered at the same dose, dosage form, and time in the placebo group. This study aims to evaluate the safety and efficacy of ketorolac in improving the prognosis of aTAAD. The primary endpoint is the composite endpoint event concerning drug-related adverse events. Secondary endpoints include drug-related adverse events, laboratory examination of blood, diagnostic imaging tests, clinical biomarkers, etc. DISCUSSION: This study has been approved by the Medical Ethics Committee of Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical College (approval number: 2023-197-02). This study is designed to evaluate the safety and efficacy of ketorolac in patients with aTAAD. All participating patients will sign an informed consent form, and the trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION: The Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074394. Registered on 4 October 2023.


Asunto(s)
Disección Aórtica , COVID-19 , Humanos , SARS-CoV-2 , Ketorolaco/efectos adversos , Pronóstico , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/cirugía , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
J Contin Educ Nurs ; : 1-6, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38567920

RESUMEN

BACKGROUND: This study investigated the impact of applying the anchored teaching mode with nursing interns on the cardiac surgery intensive care unit (CSICU). METHOD: A total of 110 interns were divided into a control group (taught through traditional methods) and an experimental group (taught using the anchored teaching mode). The anchored mode, emphasizing student-centered learning, included creating scenarios, identifying problems, using self-directed and collaborative learning, and evaluating outcomes. RESULTS: Our study found that the experimental group showed significantly higher scores in emergency response ability, nursing skills, and teaching effectiveness compared with the control group at graduation. CONCLUSION: The findings suggest that implementing the anchored teaching mode can effectively enhance the education of nursing interns on the CSICU, emphasizing the need for further research across different departments and types of hospitals. [J Contin Educ Nurs. 202x;5x(x):xx-xx.].

6.
Front Immunol ; 15: 1374270, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650938

RESUMEN

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middle-aged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC.


Asunto(s)
Neoplasias Pulmonares , Humanos , Masculino , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante/métodos , Inmunoterapia/métodos , Resultado del Tratamiento , Antígeno B7-H1/antagonistas & inhibidores , Carcinosarcoma/terapia , Carcinosarcoma/patología , Carcinosarcoma/tratamiento farmacológico
7.
Protein Expr Purif ; 219: 106475, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38552891

RESUMEN

AA139, a variant of natural antimicrobial peptide (AMP) arenicin-3, displayed potent activity against multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria. Nevertheless, there were currently few reports on the bioprocess of AA139, and the yields were less than 5 mg/L. Additionally, it was difficult and expensive to prepare AA139 through chemical synthesis due to its complex structure. These factors have impeded the further research and following clinical application of AA139. Here, we reported a bioprocess for the preparation of AA139, which was expressed in Escherichia coli (E. coli) BL21 (DE3) intracellularly in a soluble form via SUMO (small ubiquitin-related modifier) fusion technology. Then, recombinant AA139 (rAA139, refer to AA139 obtained by recombinant expression in this study) was obtained through the simplified downstream process, which was rationally designed in accordance with the physicochemical characteristics. Subsequently, the expression level of the interest protein was increased by 54% after optimization of high cell density fermentation (HCDF). Finally, we obtained a yield of 56 mg of rAA139 from 1 L culture with a purity of 98%, which represented the highest reported yield of AA139 to date. Furthermore, various characterizations were conducted to confirm the molecular mass, disulfide bonds, and antimicrobial activity of rAA139.


Asunto(s)
Péptidos Antimicrobianos , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Péptidos Antimicrobianos/genética , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/farmacología , Fermentación , Expresión Génica
8.
ACS Omega ; 9(11): 12665-12675, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38524499

RESUMEN

Currently, research surrounding low-salinity water flooding predominantly focuses on medium- to high-permeability sandstone reservoirs. Nevertheless, further investigation is necessary to implement this technique with regard to tight sandstone reservoirs. The present study comprises a series of experiments conducted on the crude oil and core of the Ordos Chang 6 reservoir to investigate the influence of ionic composition on low-salinity water flooding in tight oil reservoirs. The change in wettability on the rock surface was analyzed by using the contact angle experiment. The change in recovery rate was analyzed using a core displacement experiment. The reaction between rock fluids was analyzed using an ion chromatography experiment. Additionally, a nuclear magnetic resonance (NMR) experiment was used to analyze the mobilization law of crude oil and the change in wettability on the scale of the rock core. This led to a comprehensive discussion of the law and mechanism of enhancing the recovery rate via low-salinity water flooding from various perspectives. Experiments show that low-salinity water flooding is an effective technique for enhancing recovery in tight sandstone reservoirs. Altering the ionic composition of injected water can improve the water wettability of the rock surface and enhance recovery. Decreasing the mass concentration of Ca2+ or increasing the mass concentration of SO42- can prompt the ion-exchange reaction on the rock surface and detachment of polar components from the surface. Consequently, the wettability of the rock surface strengthens, augmenting the recovery process. Nuclear magnetic resonance experiments evidence that low-salinity water injection, with ion adjustment, significantly alters the interactions between the rock and fluid in tight sandstone reservoirs. As a result, the T2 signal amplitude decreases significantly, residual oil saturation reduces considerably, and the hydrophilic nature of the rock surface increases.

9.
Front Plant Sci ; 15: 1368135, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486854

RESUMEN

Introduction: With the depletion of wild Astragali Radix (WA) resources, imitated-wild Astragali Radix (IWA) and cultivated Astragali Radix (CA) have become the main products of Astragali Radix. However, the quality differences of three growth patterns (WA, IWA, CA) and different growth years of Astragali Radix have not been fully characterized, leading to a lack of necessary scientific evidence for their use as substitutes for WA. Methods: We innovatively proposed a multidimensional evaluation method that encompassed traits, microstructure, cell wall components, saccharides, and pharmacodynamic compounds, to comprehensively explain the quality variances among different growth patterns and years of Astragali Radix. Results and discussion: Our study showed that the quality of IWA and WA was comparatively similar, including evaluation indicators such as apparent color, sectional structure and odor, thickness of phellem, diameter and number of vessels, morphology of phloem and xylem, and the levels and ratios of cellulose, hemicellulose, lignin, sucrose, starch, water-soluble polysaccharides, total-saponins. However, the content of sucrose, starch and sorbose in CA was significantly higher than WA, and the diameter and number of vessels, total-flavonoids content were lower than WA, indicating significant quality differences between CA and WA. Hence, we suggest that IWA should be used as a substitute for WA instead of CA. As for the planting years of IWA, our results indicated that IWA aged 1-32 years could be divided into three stages according to their quality change: rapid growth period (1-5 years), stable growth period (6-20 years), and elderly growth period (25-32 years). Among these, 6-20 years old IWA exhibited consistent multidimensional comparative results, showcasing elevated levels of key active components such as water-soluble polysaccharides, flavonoids, and saponins. Considering both the quality and cultivation expenses of IWA, we recommend a cultivation duration of 6-8 years for growers. In conclusion, we established a novel multidimensional evaluation method to systematically characterize the quality of Astragali Radix, and provided a new scientific perspective for the artificial cultivation and quality assurance of Astragali Radix.

10.
Cancer Immunol Immunother ; 73(2): 24, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280010

RESUMEN

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of complementarity determining region 3 (CDR3) length distribution did not show significant differences between tumor and matched normal tissues. Moreover, analysis of the median Jaccard index indicated a limited overlap of TCR repertoire between these groups. Compared with normal tissues, a significantly lower diversity and higher clonality of TCR repertoire was observed in tumor samples, which was associated with clinical characteristics. Further analysis of transcriptional profiles demonstrated that tumor samples with high clonality showed increased expression of genes associated with CD8 + T cells. In addition, we analyzed the TCR repertoire of CD4 + T cells and CD8 + T cells isolated from tumor tissues. We identified that expanded clonotypes were predominantly in the CD8 + T cell compartment, which presented with an exhausted phenotype. Overall, we comprehensively compared TCR repertoire between penile tumor and normal tissues and demonstrated the presence of distinct T cell immune microenvironments in patients with PSCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Masculino , Humanos , Receptores de Antígenos de Linfocitos T , Neoplasias del Pene/genética , Neoplasias del Pene/metabolismo , Regiones Determinantes de Complementariedad/metabolismo , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Linfocitos T CD8-positivos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Microambiente Tumoral
11.
Mol Biol Rep ; 51(1): 98, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38206538

RESUMEN

BACKGROUND: Mutations in the receptor tyrosine kinase KIT are the main cause of gastrointestinal stromal tumor (GIST), and the KIT mutants mediated PI3 kinase activation plays a key role in the tumorigenesis of GIST. In this study, we aimed to block PI3 kinase activation by cell-permeable peptide and investigate its possible application in the treatment of GIST. METHODS AND RESULTS: We designed cell-permeable peptides based on the binding domain of PI3 kinase subunit p85 to KIT or PI3 kinase subunit p110, respectively, in order to compete for the binding between p85 and KIT or p110 and therefore inhibit the activation of PI3 kinases mediated by KIT. The results showed that the peptide can penetrate the cells, and inhibit the activation of PI3 kinases, leading to reduced cell survival and cell proliferation mediated by KIT mutants in vitro. Treatment of mice carrying germline KIT/V558A mutation, which can develop GIST, with the peptide that can compete for the binding between p85 and p110, led to reduced tumorigenesis of GIST. The peptide can further enhance the inhibition of the tumor growth by imatinib which is used as the first line targeted therapy of GIST. CONCLUSIONS: Our results showed that cell-permeable PI3 kinase competitive peptide can inhibit KIT-mediated PI3 kinase activation and tumorigenesis of GIST, providing a rationale to further test the peptide in the treatment of GIST and even other tumors with over-activation of PI3 kinases.


Asunto(s)
Tumores del Estroma Gastrointestinal , Fosfatidilinositol 3-Quinasas , Animales , Ratones , Fosfatidilinositol 3-Quinasas/genética , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Carcinogénesis/genética , Transformación Celular Neoplásica , Fosfatidilinositol 3-Quinasa , Péptidos/farmacología
12.
Ann Med Surg (Lond) ; 86(1): 245-251, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38222740

RESUMEN

Introduction and importance: The feasibility of combined tislelizumab with gemcitabine and cisplatin as a neoadjuvant regimen for muscle-invasive bladder cancer (MIBC) remains to be investigated. Case presentation: The neoadjuvant treatment not only shrunk tumours significantly but also lowered their stages from T4bN1M0, T3N0M0, and T3bN0M0 to pT1, pT0 and pTis, respectively. The treatment suppressed tumour cell proliferation and promoted luminal-to-basal transition. Clinical discussion: MIBC is an aggressive bladder cancer with poor prognosis. All three patients with MIBC benefited greatly from the neoadjuvant regimen (tislelizumab + gemcitabine + cisplatin). It appears that the effect of the treatment is independent of the levels of programmed death-ligand 1 nor the subtype of urothelial bladder cancer. Conclusion: Combination of tislelizumab with gemcitabine and cisplatin appeared to be a safe and efficacious neoadjuvant therapy for MIBC.

13.
Cell Signal ; 113: 110959, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37918465

RESUMEN

BACKGROUND: Irisin, a myokine derived from proteolytic cleavage of the fibronectin type III domain-containing protein 5 (FNDC5) protein, is crucial in protecting tissues and organs from ischemia-reperfusion (I/R) injury. However, the underlying mechanism of its action remains elusive. In this study, we investigated the expression patterns of genes associated with FNDC5 knockout to gain insights into its molecular functions. METHODS: We employed a mouse model of skeletal muscle I/R injury with FNDC5 knockout to examine the transcriptional profiles using RNA sequencing. Differentially expressed genes (DEGs) were identified and subjected to further analyses, including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) network analysis, and miRNA-transcription factor network analysis. The bioinformatics findings were validated using qRT-PCR and Western blotting. RESULTS: Comparative analysis of skeletal muscle transcriptomes between wild-type (WT; C57BL/6), WT-I/R, FNDC5 knockout (KO), and KO-I/R mice highlighted the significance of FNDC5 in both physiological conditions and I/R injury. Through PPI network analysis, we identified seven key genes (Col6a2, Acta2, Col4a5, Fap, Enpep, Mmp11, and Fosl1), which facilitated the construction of a TF-hub genes-miRNA regulatory network. Additionally, our results suggested that the PI3K-Akt pathway is predominantly involved in FNDC5 deletion-mediated I/R injury in skeletal muscle. Animal studies revealed reduced FNDC5 expression in skeletal muscle following I/R injury, and the gastrocnemius muscle with FNDC5 knockout exhibited larger infarct size and more severe tissue damage after I/R. Moreover, Western blot analysis confirmed the upregulation of Col6a2, Enpep, and Mmp11 protein levels following I/R, particularly in the KO-I/R group. Furthermore, FNDC5 deletion inhibited the PI3K-Akt signaling pathway. CONCLUSION: This study demonstrates that FNDC5 deletion exacerbates skeletal muscle I/R injury, potentially involving the upregulation of Col6a2, Enpep, and Mmp11. Additionally, the findings suggest the involvement of the PI3K-Akt pathway in FNDC5 deletion-mediated skeletal muscle I/R injury, providing novel insights into the molecular mechanisms underlying FNDC5's role in this pathological process.


Asunto(s)
MicroARNs , Daño por Reperfusión , Ratones , Animales , Metaloproteinasa 11 de la Matriz/genética , Metaloproteinasa 11 de la Matriz/metabolismo , Transcriptoma , Fibronectinas/genética , Fibronectinas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Factores de Transcripción/metabolismo , Daño por Reperfusión/metabolismo , Reperfusión , MicroARNs/genética , MicroARNs/metabolismo
14.
Aging Cell ; 23(3): e14074, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38155547

RESUMEN

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium-like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia-reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium-like behavior between young and aged mice and the underlying mechanisms. The results showed that surgery significantly increased hippocampal A1 astrocyte activation in aged compared to young mice. The high neuroinflammatory state induced by surgery resulted in glutamate accumulation in the extrasynaptic space, which subsequently decreased the excitability of pyramidal neurons and increased the PV interneurons inhibition through enhancing N-methyl-D-aspartate receptors' tonic currents in the hippocampus. These further induced the abnormal activities of the hippocampal neural networks and consequently contributed to delirium-like behavior in aged mice. Notably, the intraperitoneal administration of exendin-4, a glucagon-like peptide-1 receptor agonist, downregulated A1 astrocyte activation and alleviated delirium-like behavior in aged mice, while IL-1α, TNF-α, and C1q in combination administered intracerebroventricularly upregulated A1 astrocyte activation and induced delirium-like behavior in young mice. Therefore, our study suggested that cardiac surgery increased A1 astrocyte activation which subsequently impaired the hippocampal neural networks and triggered delirium development.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Delirio , Ratones , Animales , Astrocitos , Hipocampo/fisiología , Redes Neurales de la Computación
15.
Front Cardiovasc Med ; 10: 1237055, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38028495

RESUMEN

Background: Postoperative delirium (POD) is a significant complication observed in cardiac surgery patients, characterized by acute cognitive decline, fluctuating mental status, consciousness impairment, and confusion. Despite its impact, POD often goes undiagnosed. Postoperative fever, a common occurrence after cardiac surgery, has not been comprehensively studied in relation to delirium. This study aims to identify perioperative period factors associated with POD in patients undergoing cardiopulmonary bypass, with the potential for implementing preventive interventions. Methods: In a prospective observational study conducted between February 2023 and April 2023 at the Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, a total of 232 patients who underwent cardiac surgery were enrolled. POD assessment utilized the Confusion Assessment Method for the ICU (CAM-ICU), while high fever was defined as a bladder temperature exceeding 39°C. Statistical analysis included univariate and multivariate analyses, logistic regression, nomogram development, and internal validation. Result: The overall incidence of postoperative delirium was found to be 12.1%. Multivariate analysis revealed that postoperative lactate levels [odds ratio (OR) = 1.787], maximum temperature (OR = 11.290), and cardiopulmonary bypass time (OR = 1.015) were independent predictors of POD. A predictive nomogram for POD was developed based on these three factors, demonstrating good discrimination and calibration. The prediction model exhibited a C-statistic value of 0.852 (95% CI, 0.763-0.941), demonstrating excellent discriminatory power. Sensitivity and specificity, based on the area under the receiver operating characteristic (AUROC) curve, were 91.2% and 67.9%, respectively. Conclusion: This study underscores the high prevalence of POD in cardiac surgery patients and identifies postoperative lactate levels, cardiopulmonary bypass duration, and postoperative fever as independent predictors of delirium. The association between postoperative fever and POD warrants further investigation. These findings have implications for implementing preventive strategies in high-risk patients, aiming to mitigate postoperative complications and improve patient outcomes.

16.
Sci Rep ; 13(1): 19759, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957185

RESUMEN

To reduce the gas disaster of high gas coal seam and improve the efficiency of gas extraction by high drilling, the layout parameters of drilling holes in Pingdingshan coal mine are optimized. Based on the analysis and calculation of the "three zones" of the movement towards the overly strata of No.10 coal in Pingdingshan coal mine, the height of caving zone and fissure zone in 24,130 working face are 10.06-14.46 m and 38.75-49.95 m respectively. The elevation angle, azimuth angle and the length of high-level boreholes are studied and analyzed by COMSOL numerical simulation software. The simulation results show that the optimum layout parameters of high-level boreholes are as follows: The elevation angle of borehole should be controlled at 9°-12°, the azimuth angle should be 30°-45°, and the length of borehole should be 150 m. Then the optimum layout parameters of high-level boreholes are determined for engineering application of 24,130 working face. Borehole data onto actual mine show that the optimum layout parameters of high-level boreholes were elevation angle between 8°and 11°, azimuth angle between 30° and 42°, and length of boreholes between 145 and 155 m. The simulation results are basically consistent with the measured data. The maximum gas concentration in working face, upper corner and return air roadway is stably controlled below 1%. The safe mining of 24,130 working face is ensured, which provided a certain reference value of gas control in the goaf of Pingdingshan mine and adjacent mines.

17.
J Org Chem ; 88(20): 14619-14633, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37789599

RESUMEN

Construction of pyrrolidinyl-spiroindoles with easily available starting materials has attracted considerable attention from the synthesis community and is in great demand. Here, we describe a base-promoted formal (3 + 2) cycloaddition of α-halohydroxamates with alkenyl-iminoindolines. The present methodology features mild reaction conditions and a broad substrate scope with up to 99% yield and excellent diastereoselectivity. The versatility of this approach is demonstrated through valuable synthetic transformations. Preliminary mechanistic studies shed light on the mechanism of this cycloaddition process.

18.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4634-4646, 2023 Sep.
Artículo en Chino | MEDLINE | ID: mdl-37802802

RESUMEN

Dead heart is an important trait of pith-decayed Scutellariae Radix. The purpose of this study was to clarify the scientific connotation of the dead heart using multi-omics. Metabolomics and transcriptomics combined with multivariate statistical analysis such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were used to systematically compare the differences in chemical composition and gene expression among phloem, outer xylem and near-dead xylem of pith-decayed Scutella-riae Radix. The results revealed significant differences in the contents of flavonoid glycosides and aglycones among the three parts. Compared with phloem and outer xylem, near-dead xylem had markedly lowered content of flavonoid glycosides(including baicalin, norwogonin-7-O-ß-D-glucuronide, oroxylin A-7-O-ß-D-glucuronide, and wogonoside) while markedly increased content of aglycones(including 3,5,7,2',6'-pentahydroxy dihydroflavone, baicalin, wogonin, and oroxylin A). The differentially expressed genes were mainly concentrated in KEGG pathways such as phenylpropanoid metabolism, flavonoid biosynthesis, ABC transporter, and plant MAPK signal transduction pathway. This study systematically elucidated the material basis of the dead heart of pith-decayed Scutellariae Radix with multiple growing years. Specifically, the content of flavonoid aglycones was significantly increased in the near-dead xylem, and the gene expression of metabolic pathways such as flavonoid glycoside hydrolysis, interxylary cork development and programmed apoptosis was significantly up-regulated. This study provided a theoretical basis for guiding the high-quality production of pith-decayed Scutellariae Radix.


Asunto(s)
Medicamentos Herbarios Chinos , Medicamentos Herbarios Chinos/química , Scutellaria baicalensis/genética , Scutellaria baicalensis/química , Glucurónidos , Multiómica , Flavonoides/química
19.
Perfusion ; : 2676591231210459, 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37885091

RESUMEN

OVERVIEW: Acute type A aortic dissection (ATAAD) with persistent coma is a life-threatening condition associated with high mortality and poor neurological outcomes. The optimal timing for surgical intervention in these patients remains uncertain, and many patients are not eligible for surgery due to their poor prognosis. DESCRIPTION: In this case, a 53-year-old man with hypertension presented to the emergency department in a coma that had lasted for 9 hours. The patient was diagnosed with ATAAD and underwent the "Drum Tower Hospital" strategy, which involved preoperative assessments, including computed tomography angiography (CTA) and quantitative electroencephalogram (qEEG) monitoring. Surgical interventions, such as emergency stenting and aortic replacement, were performed to restore blood flow and repair the aorta. Postoperative monitoring, including qEEG, showed improvements in brain function. Despite the patient experiencing hemiplegia and a neurological deficit, the "Drum Tower Hospital" strategy, guided by comprehensive brain assessments, showed promise in managing ATAAD with coma. However, further research is needed to establish effective treatment strategies for these patients. Overall, ATAAD with persistent coma is a critical condition with limited treatment options. The "Drum Tower Hospital" strategy, supported by multimodal brain assessment, offers a potential approach to improve outcomes in these patients.

20.
Sci Data ; 10(1): 741, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880252

RESUMEN

This study presents a novel ensemble of surface ozone (O3) generated by the LEarning Surface Ozone (LESO) framework. The aim of this study is to investigate the spatial and temporal variation of surface O3. The LESO ensemble provides unique and accurate hourly (daily/monthly/yearly as needed) O3 surface concentrations on a fine spatial resolution of 0.1◦ × 0.1◦ across China, Europe, and the United States over a period of 10 years (2012-2021). The LESO ensemble was generated by establishing the relationship between surface O3 and satellite-derived O3 total columns together with high-resolution meteorological reanalysis data. This breakthrough overcomes the challenge of retrieving O3 in the lower atmosphere from satellite signals. A comprehensive validation indicated that the LESO datasets explained approximately 80% of the hourly variability of O3, with a root mean squared error of 19.63 µg/m3. The datasets convincingly captured the diurnal cycles, weekend effects, seasonality, and interannual variability, which can be valuable for research and applications related to atmospheric and climate sciences.

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