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Background: Acute respiratory distress syndrome (ARDS) is a leading cause of postoperative respiratory failure after cardiac surgery, and the mortality rate is extremely high. Although prone positioning (PP) may be safe and effective for ARDS, it is still not widely adopted in cardiac surgery patients. We aimed to assess the efficacy and safety of early PP in ARDS after cardiac surgery. Methods: This is a single-center retrospective cohort study. We included adult intensive care unit (ICU) patients who developed ARDS with arterial pressure of oxygen to fraction of oxygen ratio (P/F) ≤200 mmHg within 72 hours after cardiac surgery between 1 January 2019 and 1 August 2023. The outcomes were P/F after 1 session of PP, duration of mechanical ventilation (MV) and ICU stay, and adverse events. Results: In total, 79 patients who underwent PP and 87 patients who underwent supine position (SP) were included. The mean time to perform PP after ICU admission was 38.0 hours. The P/F improved significantly after 1 session of PP treatment [160.0 (127.8-184.3) vs. 275.0 (220.0-325.0) mmHg, P<0.001], the duration of MV and ICU stay in the PP group were significantly shorter than those in the SP group [84.0 (64.0-122.0) vs. 120.0 (97.0-182.0) h, P<0.001; 6.0 (5.0-8.0) vs. 8.0 (6.0-12.0) days, P<0.001, respectively]. No adverse events were observed during the PP even in patients with intra-aortic balloon pump (IABP). Conclusions: Early PP treatment is effective and safe for patients with moderate to severe ARDS after cardiac surgery and it is even safe in a subgroup placed with IABP.

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Protein deterioration caused by ice crystals is an important factors affecting the frozen storage of fish. In this study, antifreeze peptides extracted from hydrolysates of sea cucumber intestinal protein with inhibition of protein denaturation were screened and characterized. The peptide Leu-Pro-Glu-Phe-Thr-Glu-Glu-Glu-Lys (LPEFTEEEK), derived from neutral protease hydrolysates of sea cucumber intestinal protein, was investigated for its potential to enhance the quality of salmon fillets during three freeze-thaw cycles. The results showed that the application of LPEFTEEEK effectively maintained the texture of fish fillets, as well as the oxidative and conformation stability of myofibrillar protein during the freezing process. Additionally, molecular dynamics simulations verified that LPEFTEEEK could bind to ice crystals and inhibit their recrystallization, thus preventing organisms from being damaged by freezing. This suggests that LPEFTEEEK holds significant promise as a novel cryoprotective agent for marine-derived antifreeze peptides.

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Objective: Analyze women treated with underwent cold knife conization (CKC) to remove advanced squamous intraepithelial lesions (CIN) of the cervix. The histopathological upgrading of the lesions previously detected on vaginal biopsy and postoperative pregnancy outcomes of were investigated, to identify high-risk subgroups in women. Methods: A retrospective study was conducted at the First Central Hospital of Baoding City from June 2019 to December 2022 to analyze confirmed cases of Cervical Intraepithelial Neoplasia CIN-II and CIN-III. Investigation of pathological changes in postoperative pathological tissues, and to perform binary logistic analysis to identify risk factors for histopathological escalation in postoperative lesions. We analyze the effects of CKC surgery on pregnancy outcomes in patients by comparing against a control group of healthy pregnant women. Results: Out of the 176 patients diagnosed with CIN-II who underwent cervical biopsy, 39 (22.16%) were found to have a final specimen diagnosis of CIN-III, while 7 (3.98%) were downgraded to CIN-I. Among the 108 patients diagnosed with CIN-III who underwent cervical biopsy, 7 cases (6.48%) were ultimately confirmed to have CIN-III. Ki67-positive, p16-positive (OR = 1.13, 95% CI 1.01-1.15), and colposcopy biopsy for CIN-II (OR = 1.59, 95% CI 1.33-3.6) were independent risk factors for pathological upgrade after CKC. Compared with healthy pregnant women, CIN patients had higher rates of premature birth (14.4%), premature rupture of the fetal membrane (13.6%), and cesarean section (37.5%) (P < 0.05). The mode of conception, abortion rate, ectopic pregnancy rate, and postpartum hemorrhage were not different between healthy pregnant women and CIN patients (P > 0.05). Conclusion: Following cervical multi-point biopsy or CKC, along with pathological examination, the accurate diagnosis of cervical lesions is crucial as it allows for more precise identification of such lesions. Additionally, CKC increases the risk of premature birth, premature rupture of membranes, and the need for cesarean section.

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Rationale: Acute kidney injury (AKI) has substantial rates of mortality and morbidity, coupled with an absence of efficacious treatment options. AKI commonly transits into chronic kidney disease (CKD) and ultimately culminates in end-stage renal failure. The interferon-stimulated gene 15 (ISG15) level was upregulated in the kidneys of mice injured by ischemia-reperfusion injury (IRI), cisplatin, or unilateral ureteral obstruction (UUO), however, its role in AKI development and subsequent AKI-to-CKD transition remains unknown. Methods: Isg15 knockout (Isg15 KO) mice challenged with bilateral or unilateral IRI, cisplatin, or UUO were used to investigate its role in AKI. We established cellular models with overexpression or knockout of ISG15 and subjected them to hypoxia-reoxygenation, cisplatin, or transforming growth factor- ß1 (TGF-ß1) stimulation. Renal RNA-seq data obtained from AKI models sourced from public databases and our studies, were utilized to examine the expression profiles of ISG15 and its associated genes. Additionally, published single cell RNA-seq data from human kidney allograft biopsies and mouse IRI model were analyzed to investigate the expression patterns of ISG15 and the type I TGF-ß receptor (TGFßR1). Western blotting, qPCR, co-immunoprecipitation, and immunohistochemical staining assays were performed to validate our findings. Results: Alleviated pathological injury and renal function were observed in Isg15 KO mice with IRI-, cisplatin-, or UUO-induced AKI and the following AKI-to-CKD transition. In hypoxia-reoxygenation, cisplatin or TGF-ß1 treated HK-2 cells, knockout ISG15 reduced stimulus-induced cell fibrosis, while overexpression of ISG15 with modification capacity exacerbated cell fibrosis. Immunoprecipitation assays demonstrated that ISG15 promoted ISGylation of TGFßR1, and inhibited its ubiquitination. Moreover, knockout of TGFßR1 blocked ISG15's fibrosis-exacerbating effect in HK-2 cells, while overexpression of TGFßR1 abolished the renal protective effect of ISG15 knockout during IRI-induced kidney injury. Conclusions: ISG15 plays an important role in the development of AKI and subsequent AKI-to-CKD transition by promoting TGFßR1 ISGylation.

Asunto(s)

Lesión Renal Aguda , Cisplatino , Citocinas , Ratones Noqueados , Daño por Reperfusión , Ubiquitinas , Animales , Humanos , Masculino , Ratones , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Cisplatino/farmacología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Riñón/metabolismo , Riñón/patología , Ratones Endogámicos C57BL , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/genética , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Ubiquitinas/metabolismo , Ubiquitinas/genética , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/genética

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Sepsis is a systemic inflammatory response syndrome caused by a dysregulated host response to infection. CD4+T cell reduction is crucial to sepsis-induced immunosuppression. Pyroptosis, a programmed necrosis, is concerned with lymphocytopenia. Peroxisome proliferator-activated receptor gamma (PPARγ) regulated by upstream mTOR, exerts anti-pyroptosis effects. To investigate the potential effects of mTOR-PPARγ on sepsis-induced CD4+T cell depletion and the underlying mechanisms, we observed mTOR activation and pyroptosis with PPARγ-Nrf suppression through cecal ligation and puncture (CLP) sepsis mouse model. Further mechanism research used genetically modified mice with T cell-specific knockout mTOR or Tuberous Sclerosis Complex1 (TSC1). It revealed that mTOR mediated CD4 + T cell pyroptosis in septic mice by negatively regulating the PPARγ-Nrf2 signaling pathway. Taken together, mTOR-PPARγ-Nrf2 signaling mediated the CD4+ T cell pyroptosis in sepsis, contributing to CD4+T cell depletion and immunosuppression.

Asunto(s)

Linfocitos T CD4-Positivos , Factor 2 Relacionado con NF-E2 , PPAR gamma , Piroptosis , Sepsis , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , PPAR gamma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/genética , Sepsis/inmunología , Sepsis/metabolismo , Linfocitos T CD4-Positivos/inmunología , Serina-Treonina Quinasas TOR/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Masculino , Modelos Animales de Enfermedad , Humanos

RESUMEN

BACKGROUND: We evaluated the influence of different partial carbon dioxide pressure (PaCO2) levels on organ perfusion in patients with respiratory failure receiving pressure-support ventilation with veno-venous extracorporeal membrane oxygenation (V-V ECMO). METHODS: In this twelve patients prospective study, ECMO gas-flow was decreased from baseline (PaCO2 < 40 mmHg) until PaCO2 increased by 5-10 mmHg (High-CO2 phase). Resistance indices of gut, spleen, and snuffbox artery, the peripheral perfusion index (PPI), and heart rate variability were measured at baseline and High-CO2 phase. RESULTS: When PaCO2 increased from 36 (36-37) mmHg at baseline to 42 (41-43) mmHg in the High-CO2 phase (p < 0.001), PPI decreased significantly (p = 0.026). The snuffbox artery (p = 0.022), superior mesenteric artery (p = 0.042), and spleen (p = 0.012) resistance indices increased significantly. The root mean square of successive differences (RMSSD) decreased from 19.5(18.1-22.7) to 15.9(14.4-18.6) ms (p = 0.034), and the ratio of low-frequency to high-frequency components(LF/HF) increased from 0.47 ± 0.23 to 0.70 ± 0.38 (p = 0.013). CONCLUSIONS: High PaCO2 might cause decreased peripheral tissue and visceral organ perfusion through autonomic nervous system in patients with respiratory failure undergoing PSV with V-V ECMO.

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Dióxido de Carbono , Oxigenación por Membrana Extracorpórea , Presión Parcial , Insuficiencia Respiratoria , Humanos , Oxigenación por Membrana Extracorpórea/métodos , Estudios Prospectivos , Masculino , Femenino , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/fisiopatología , Persona de Mediana Edad , Adulto , Anciano , Frecuencia Cardíaca , Bazo

RESUMEN

Background: The aim of this study was to clarify the relationship between expression level of CTLA-4 on CD4+ T cells and sepsis-associated immunosuppression (SAI), and to elucidate the possible mechanism of mTOR pathway mediated autophagic-lysosomal disorder in regulating CTLA-4 expression. Methods: We enrolled 63 sepsis patients admitted to our ICU between January 1 and June 30, 2023. Peripheral blood mononuclear cells were isolated from the patients within 24 hours of recruitment. Expression levels of mTOR, P62, LC3II, and CTLA-4 on circulating CD4+ T lymphocytes were quantitated using flow cytometry. The association of these markers and relationship between CTLA-4 expression and the incidence of SAI and 28-day mortality were comprehensively analyzed. Results: Compared with non-immunosuppressed patients with sepsis, patients with SAI had a higher 28-day mortality rate (37.5% vs 13.0%, P=0.039) and higher CTLA-4 mean fluorescence intensity (MFI) on CD4+ T cells (328.7 versus 78.7, P<0.0001). CTLA-4 MFI on CD4+ cells was independently associated with the occurrence of SAI (95% confidence interval: 1.00-1.14, P=0.044). In patients with sepsis and SAI, non-survivors had higher CTLA-4 expression than survivors (sepsis: 427.5 versus 130.6, P=0.002; and SAI: 506.7 versus 225.2, P<0.0001). The sensitivity and specificity of CTLA-4 MFI at predicting 28-day mortality in patients with SAI was 100% and 80% respectively with the cutoff value of 328.7 and the area under the curve of 0.949. The MFI of mTOR, P62, and LC3II on CD4+ T cells were statistically higher in patients with SAI than in non-immunosuppressed patients (267.2 versus 115.9, P<0.0001; 314.8 versus 173.7, P<0.0001; and 184.7 versus 1123.5, P=0.012, respectively); P62 and LC3II were markedly higher in non-survivors than in survivors of sepsis (302.9 versus 208.9, P=0.039; and 244.3 versus 122.8, P<0.0001 respectively). The expression of CTLA-4 statistically correlated with that of LC3II in patients with sepsis, patients with SAI, and patients with SAI who did not survive (correlation coefficient: 0.69, 0.68, and 0.73, respectively, P<0.0001). Conclusions: CTLA-4 overexpression on CD4+ T cells was markedly associated with the incidence of SAI and had great relevance to 28-day mortality. mTOR pathway mediated autophagic-lysosomal disorder showed significant association with CTLA-4 expression.

Asunto(s)

Autofagia , Linfocitos T CD4-Positivos , Antígeno CTLA-4 , Sepsis , Serina-Treonina Quinasas TOR , Humanos , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Femenino , Antígeno CTLA-4/metabolismo , Sepsis/inmunología , Sepsis/mortalidad , Sepsis/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Persona de Mediana Edad , Anciano , Tolerancia Inmunológica

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Sepsis has been the leading cause of death in ICU patients. CD4+ T cells are the mainstay of the body's immune system, and the depletion of CD4+ T cells in sepsis is of great concern. Cytotoxic T lymphocyte-associated protein 4 (CTLA4) is a negative immunomodulator for T cell activation and degradation through the autophagy-lysosome pathway. Mammalian target of rapamycin (mTOR) is the most classical upstream regulator of autophagy. With a mouse model of sepsis through cecal ligation and puncture (CLP), T cell specific-mTOR/tuberous sclerosis complex 1 (TSC1)-knockout mice, and bafilomycin A1, a specific autophagosome-lysosome (A-L) fusion inhibitor, we primarily proved that mTOR could modulate the expression and accumulation of CTLA4 by regulating the onset process of autophagy such as A-L fusion. Given such a regulatory relationship, targeting mTOR could provide new light to improve immune function in sepsis, and the prospect of using rapamycin in the clinic would be worth exploring further.

Asunto(s)

Autofagia , Linfocitos T CD4-Positivos , Antígeno CTLA-4 , Ratones Noqueados , Sepsis , Serina-Treonina Quinasas TOR , Animales , Sepsis/metabolismo , Ratones , Linfocitos T CD4-Positivos/metabolismo , Antígeno CTLA-4/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Ratones Endogámicos C57BL , Macrólidos/farmacología , Masculino

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Filoviruses are some of the most lethal viruses in the modern world, and increasing numbers of filovirus species and genera have been discovered in recent years. Despite the potential severity of filovirus outbreaks in the human population, comparably few sensitive pan-filovirus RT-PCR assays have been described that might facilitate early detection and prevention. Here, we present a new pan-filovirus RT-PCR assay targeting the L polymerase gene for detection of all known mammalian filoviruses. We demonstrate the detection of 10 synthetic filovirus RNA templates with analytical sensitivity ranging from 178 to 3,354 copies/mL, without cross-reactivity on 10 non-filoviral human viral species. We verified assay performance on 10 inactivated filovirus isolates, yielding initial sensitivities of 0.012-44.17 TCID50/mL. We coupled this broadly reactive RT-PCR with a deep sequencing workflow that is amenable to high-throughput pooling to maximize detection and discovery potential. In summary, this pan-filovirus RT-PCR assay targets the most conserved filovirus gene, offers the widest breadth of coverage to date, and may help in the detection and discovery of novel filoviruses.IMPORTANCEFiloviruses remain some of the most mysterious viruses known to the world, with extremely high lethality rates and significant pandemic potential. Yet comparably few filovirus species and genera have been discovered to date and questions surround the definitive host species for zoonotic infections. Here, we describe a novel broadly reactive RT-PCR assay targeting the conserved L polymerase gene for high-throughput screening for filoviruses in a variety of clinical and environmental specimens. We demonstrate the assay can detect all known mammalian filoviruses and determine the sensitivity and specificity of the assay on synthetic RNA sequences, inactivated filovirus isolates, and non-filoviral species.

Asunto(s)

Infecciones por Filoviridae , Filoviridae , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Filoviridae/genética , Filoviridae/aislamiento & purificación , Filoviridae/clasificación , Humanos , Animales , Infecciones por Filoviridae/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , ARN Viral/genética , Sensibilidad y Especificidad , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mamíferos/virología , Ensayos Analíticos de Alto Rendimiento/métodos , Proteínas Virales/genética

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BACKGROUND: The therapeutic strategies for acute ischemic stroke were faced with substantial constraints, emphasizing the necessity to safeguard neuronal cells during cerebral ischemia to reduce neurological impairments and enhance recovery outcomes. Despite its potential as a neuroprotective agent in stroke treatment, Chikusetsu saponin IVa encounters numerous challenges in clinical application. RESULT: Brain-targeted liposomes modified with THRre peptides showed substantial uptake by bEnd. 3 and PC-12 cells and demonstrated the ability to cross an in vitro blood-brain barrier model, subsequently accumulating in PC-12 cells. In vivo, they could significantly accumulate in rat brain. Treatment with C-IVa-LPs-THRre notably reduced the expression of proteins in the P2RX7/NLRP3/Caspase-1 pathway and inflammatory factors. This was evidenced by decreased cerebral infarct size and improved neurological function in MCAO rats. CONCLUSION: The findings indicate that C-IVa-LPs-THRre could serve as a promising strategy for targeting cerebral ischemia. This approach enhances drug concentration in the brain, mitigates pyroptosis, and improves the neuroinflammatory response associated with stroke.

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Barrera Hematoencefálica , Accidente Cerebrovascular Isquémico , Liposomas , Fármacos Neuroprotectores , Piroptosis , Ratas Sprague-Dawley , Saponinas , Animales , Saponinas/farmacología , Saponinas/química , Piroptosis/efectos de los fármacos , Ratas , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Liposomas/química , Masculino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Células PC12 , Ácido Oleanólico/farmacología , Ácido Oleanólico/química , Ácido Oleanólico/análogos & derivados , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo

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Feature selection is a critical component of data mining and has garnered significant attention in recent years. However, feature selection methods based on information entropy often introduce complex mutual information forms to measure features, leading to increased redundancy and potential errors. To address this issue, we propose FSCME, a feature selection method combining Copula correlation (Ccor) and the maximum information coefficient (MIC) by entropy weights. The FSCME takes into consideration the relevance between features and labels, as well as the redundancy among candidate features and selected features. Therefore, the FSCME utilizes Ccor to measure the redundancy between features, while also estimating the relevance between features and labels. Meanwhile, the FSCME employs MIC to enhance the credibility of the correlation between features and labels. Moreover, this study employs the Entropy Weight Method (EWM) to evaluate and assign weights to the Ccor and MIC. The experimental results demonstrate that FSCME yields a more effective feature subset for subsequent clustering processes, significantly improving the classification performance compared to the other six feature selection methods.

Asunto(s)

Algoritmos , Minería de Datos , Entropía , Humanos , Minería de Datos/métodos , Bases de Datos Factuales , Análisis por Conglomerados

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In this study, ultrafiltration fractions (<3 k Da, LMH; >3 k Da, HMH) and solid-phase extraction fractions (hydrophilic hydrolysate, HIH; hydrophobic hydrolysate, HOH) from trypsin hydrolysate purified from croceine croaker (Pseudosciaena crocea) isolate were obtained to investigate the cryoprotective effects of the different fractions, achieved by means of maceration of turbot fish meat after three freeze-thaw cycles. Alterations in the texture, color, moisture loss, myofibrillar protein oxidation stability and conformation, and microstructure of the fish were analyzed after freezing and thawing. The results demonstrate that HIH maximized the retention of fish texture, reduced moisture loss, minimized the oxidation and aggregation of myofibrillar proteins, and stabilized the secondary and tertiary structures of myofibrillar proteins compared to the control group. In conclusion, the HIH component in the trypsin hydrolysates of croceine croaker significantly contributes to minimizing freeze damage in fish meat and acts as an anti-freezing agent with high industrial application potential.

RESUMEN

BACKGROUND: Accumulative evidence suggested that the oxytocin system plays a role in socio-emotional disorders, although its role in neuroinflammation-induced anxiety remains unclear. METHOD: In the present study, anxiety-like behavior was induced in cohorts of animals through repeated lipopolysaccharide (LPS, 0.5 mg/kg, daily, Escherichia coli O55:B5) i.p. injections for seven consecutive days. These different cohorts were subsequently used for anxiety-like behavior assessment with open field test, elevated plus maze, and novelty-suppressed feeding test or for electrophysiology (EEG) recordings of miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs), or local field potential (LFP) in vivo or ex vivo settings. Samples of the anterior cingulate cortex (ACC) from some cohorts were harvested to conduct immunostaining or western blotting analysis of oxytocin, oxytocin receptor, CamkII, GABA, vGAT, vGLUT2, and c-fos. The dendritic spine density was assessed by Golgi-Cox staining. RESULTS: Repeated LPS injections induced anxiety-like behavior with concurrent decreases of oxytocin, vGLUT2, mEPSC, dendritic spine, c-fos, membrane excitability, and EEG beta and gamma oscillations, but increased oxytocin receptor and vGAT expressions in the ACC; all these changes were ameliorated by oxytocin intranasal or local brain (via cannula) administration. CONCLUSION: Taken together, our data suggested that oxytocin system may be a therapeutic target for developing treatment to tackle neuroinflammation-induced anxiety.

Asunto(s)

Ansiedad , Giro del Cíngulo , Lipopolisacáridos , Enfermedades Neuroinflamatorias , Oxitocina , Animales , Oxitocina/farmacología , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/metabolismo , Ratones , Ansiedad/fisiopatología , Masculino , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Lipopolisacáridos/farmacología , Modelos Animales de Enfermedad , Receptores de Oxitocina/metabolismo , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología

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Background: The relationship between Hashimoto's thyroiditis (HT) and papillary thyroid microcarcinoma (PTMC) is controversial. These include central lymph node metastasis (CLNM), which affects the prognosis of PTMC patients. This study aimed to establish a predictive model combining ultrasonography and clinicopathological features to accurately evaluate latent CLNM in PTMC patients with HT at the clinical lymph node-negative (cN0) stage. Methods: In this study, 1102 PTMC patients who received thyroidectomy and central cervical lymph node dissection (CLND) from the First Affiliated Hospital of Shandong First Medical University from January 2021 to December 2022 and the 960th Hospital of PLA from January 2021 to December 2022 were jointly collected. The clinical differences between PTMCs with HT and those without HT were compared. A total of 373 PTMCs with HT in cN0 were randomly divided into a training cohort and a validation cohort. By analyzing and screening the risk factors of CLNM, a nomogram model was established and verified. The predictive performance was measured by the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA). Results: The ratio of central lymph node metastasis (CLNMR) in PTMCs with HT was 0.0% (0.0%, 15.0%) and 7.7% (0.0%, 40.0%) in the non-HT group (P<0.001). Multivariate logistic regression analysis showed that age, gender, calcification, adjacent to trachea or capsule, and TPOAB were predictors of CLNM in PTMCs with HT. The areas under the curve (AUC) of the prediction models in the training cohort and the validation cohort were 0.835 and 0.825, respectively, which showed good differentiation ability. DCA indicates that the prediction model also has high net benefit and clinical practical value. Conclusion: This study found that CLN involvement was significantly reduced in PTMC patients with HT, suggesting that different methods should be used to predict CLNM in PTMC patients with HT and without HT, to more accurately assist preoperative clinical evaluation. The actual CLNM situation of PTMCs with HT in cN0 can be accurately predicted by the combination of ultrasonography and clinicopathological features.

Asunto(s)

Carcinoma Papilar , Enfermedad de Hashimoto , Metástasis Linfática , Neoplasias de la Tiroides , Humanos , Enfermedad de Hashimoto/patología , Enfermedad de Hashimoto/complicaciones , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/diagnóstico por imagen , Femenino , Metástasis Linfática/patología , Masculino , Adulto , Persona de Mediana Edad , Carcinoma Papilar/patología , Carcinoma Papilar/cirugía , Pronóstico , Nomogramas , Tiroidectomía , Ultrasonografía , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Estudios Retrospectivos , Curva ROC

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Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Asunto(s)

Reflujo Gastroesofágico , Reflujo Laringofaríngeo , Inhibidores de la Bomba de Protones , Humanos , Reflujo Laringofaríngeo/fisiopatología , Reflujo Laringofaríngeo/diagnóstico , Reflujo Laringofaríngeo/terapia , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/terapia , Reflujo Gastroesofágico/diagnóstico , Inhibidores de la Bomba de Protones/uso terapéutico , Resultado del Tratamiento , Estilo de Vida

RESUMEN

Background: This study aimed to investigate the effect and mechanism of Pentraxin 3 (PTX3) on myocardial injury in sepsis. Methods: Thirty male C57BL/6 mice were randomly assigned to Groups A, B, or C. Mice in Groups A and B were injected with unloaded lentivirus, while mice in Group C were injected with lentivirus encoding PTX3 overexpression. Seven days after injection, septic myocardial injury mouse models were constructed following intraperitoneal injection with LPS in Groups B and C, and mice in Group A were intraperitoneally injected with normal saline. Cardiac function was examined using echocardiography; pathological variation of myocardial cells was measured through HE staining, transmission electron microscopy, and TUNEL staining; and Western blot was used to measure the expression of PI3K/AKT/mTOR pathway-related, autophagy-related, and apoptosis-related proteins in mice myocardial cells. Results: PTX3 significantly improved cardiac function and structure in sepsis-stricken mice, and PTX3 alleviated cardiac damage caused by sepsis. PTX3 reduced the relative protein expression of p-PI3K, p-AKT, mTOR, LC3I/II, Beclin, ATG5, Bax, Caspase-3, and Caspase-9 in septic mouse cardiomyocytes and increased the relative protein expression of Bcl-2. Conclusion: PTX3 can attenuate myocardial injury in sepsis due to the down-regulation of apoptosis and autophagy induced by the PI3K/AKT/mTOR pathway.

Asunto(s)

Apoptosis , Autofagia , Proteína C-Reactiva , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Sepsis , Serina-Treonina Quinasas TOR , Animales , Masculino , Ratones , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/genética , Modelos Animales de Enfermedad , Regulación hacia Abajo , Ratones Endogámicos C57BL , Miocardio/patología , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sepsis/metabolismo , Sepsis/genética , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo

RESUMEN

ABSTRACT: Objective: In this study, our aim was to examine the effects of levosimendan on diaphragmatic dysfunction in patients with sepsis, as well as assess its impact on respiratory muscle contractility and the outcome of weaning. Methods: This was a single-blind, randomized, controlled trial. Patients with diaphragmatic dysfunction and failure of spontaneous breathing trials (SBTs) were randomly and equally assigned to the experimental and control groups. The experimental group received levosimendan at a loading dose of 6 µg/kg for 10 min, followed by a continuous infusion at 0.2 µg/kg/min. The control group received an equivalent dose of a placebo. The preadministration and postadministration respiratory mechanics parameters of the patients were recorded. Evaluation of the effect of levosimendan on patients with sepsis-induced diaphragm dysfunction comprised arterial blood gas analysis as well as ultrasound measurements of diaphragm excursion (DE), diaphragm thickness (DT), diaphragm thickening fraction (TFdi), and diaphragm-rapid shallow breathing index (D-RSBI). Results: Forty-four patients were enrolled in the study. We found that postadministration of levosimendan, the patients' tidal volume (GCSMV) increased, whereas the D-RSBI decreased, and the partial pressure of carbon dioxide (PACO 2 ) decreased when compared to the preadministration levels. Additionally, following levosimendan administration, patients showed increased DE and pressure support (PS) when compared to before administration (1.14 ± 0.177 vs. 1.22 ± 0.170 cm and 0.248 ± 0.03 vs. 0.284 ± 0.06, respectively) and decreased D-RSBI (22.76 ± 6.14 vs. 20.06 ± 6.04, respectively), all of which were statistically significant ( P < 0.05). In contrast, in the control group of patients, there were no statistically significant differences in the postadministration levels of DE, TFdi, and D-RSBI as compared to the preadministration period ( P > 0.05). Furthermore, in terms of weaning outcomes, we did not find any statistically significant difference in the number of patients in the two groups who eventually underwent weaning ( P = 0.545). Conclusion: In this study, we found that levosimendan enhanced diaphragm contractile function. However, further investigations are required to explore its effect on weaning outcomes in patients undergoing mechanical ventilation.

Asunto(s)

Diafragma , Hidrazonas , Piridazinas , Sepsis , Simendán , Humanos , Simendán/uso terapéutico , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Diafragma/efectos de los fármacos , Diafragma/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Piridazinas/uso terapéutico , Hidrazonas/uso terapéutico , Anciano , Método Simple Ciego , Adulto , Análisis de los Gases de la Sangre

Asunto(s)

Delirio , Procedimientos Ortopédicos , Fenotipo , Complicaciones Posoperatorias , Humanos , Delirio/etiología , Complicaciones Posoperatorias/etiología , Anciano , Procedimientos Ortopédicos/efectos adversos , Femenino , Inflamación/etiología , Masculino , Anciano de 80 o más Años

RESUMEN

The pathogenesis of Alzheimer's disease (AD) is extremely intricate, which makes AD patients almost incurable. Recent studies have demonstrated that analyzing multi-modal data can offer a comprehensive perspective on the different stages of AD progression, which is beneficial for early diagnosis of AD. In this paper, we propose a deep self-reconstruction fusion similarity hashing (DS-FSH) method to effectively capture the AD-related biomarkers from the multi-modal data and leverage them to diagnose AD. Given that most existing methods ignore the topological structure of the data, a deep self-reconstruction model based on random walk graph regularization is designed to reconstruct the multi-modal data, thereby learning the nonlinear relationship between samples. Additionally, a fused similarity hash based on anchor graph is proposed to generate discriminative binary hash codes for multi-modal reconstructed data. This allows sample fused similarity to be effectively modeled by a fusion similarity matrix based on anchor graph while modal correlation can be approximated by Hamming distance. Especially, extracted features from the multi-modal data are classified using deep sparse autoencoders classifier. Finally, experiments conduct on the AD Neuroimaging Initiative database show that DS-FSH outperforms comparable methods of AD classification. To conclude, DS-FSH identifies multi-modal features closely associated with AD, which are expected to contribute significantly to understanding of the pathogenesis of AD.

Asunto(s)

Enfermedad de Alzheimer , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/diagnóstico , Humanos , Algoritmos , Aprendizaje Profundo , Imagen por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/métodos , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Imagen Multimodal/métodos

RESUMEN

α-Amylase, essential for carbohydrate digestion, relies on calcium (Ca) for its structural integrity and enzymatic activity. This study explored the inhibitory effect of salmon bone peptides on α-amylase activity through their interaction with the enzyme's Ca-binding sites. Among the various salmon bone hydrolysates, salmon bone trypsin hydrolysate (SBTH) exhibited the highest α-amylase inhibition. The peptide IEELEEELEAER (PIE), with a sequence of Ile-Glu-Glu-Leu-Glu-Glu-Glu-Glu-Leu-Glu-Ala-Glu-Arg from SBTH, was found to specifically target the Ca-binding sites in α-amylase, interacting with key residues such as Asp206, Trp203, His201, etc. Additionally, cellular experiments using 3 T3-L1 preadipocytes indicated PIE's capability to suppress adipocyte differentiation, and decreases in intracellular triglycerides, total cholesterol, and lipid accumulation. In vivo studies also showed a significant reduction in weight gain in the group treated with PIE(6.61%)compared with the control group (33.65%). These findings suggest PIE is an effective α-amylase inhibitor, showing promise for obesity treatment.