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OBJECTIVE: To investigate the association between atherogenic index of plasma (AIP) and kidney stones (KS) occurrence and recurrence. METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. Non-pregnant adults who provided complete information on AIP and KS were included in the analyses. AIP was calculated as log (triglyceride/high-density lipoprotein cholesterol). KS was ascertained with questionnaires. Weighted multivariable logistic regression model and restricted cubic spline (RCS) were applied to examine the associations between AIP and KS occurrence and recurrence. RESULTS: A total of 6488 subjects (weighted mean age 43.19 years and 49.26% male) with a weighted mean AIP of 0.66 were included in this study. The multivariable-adjusted OR for nephrolithiasis occurrence across consecutive tertiles was 1.00 (reference), 1.21 (95% CI: 0.90-1.62), and 1.85 (95% CI: 1.39-2.48), respectively. Moreover, each SD increment of AIP was associated with a 50% (OR:1.50, 95% CI: 1.25-1.81) higher risk of nephrolithiasis recurrence. RCSs showed significant and linear dose-response relationships between AIP and nephrolithiasis occurrence (p-overall = 0.006, p-nonlinear = 0.689) and recurrence (p-overall = 0.001, p-nonlinear = 0.848). The positive associations between AIP and nephrolithiasis occurrence and recurrence persisted in sensitivity analyses, suggesting the robustness of the results. CONCLUSION: In the current US nationally representative cross-sectional study, AIP was positively associated with KS occurrence and recurrence.

Asunto(s)

Aterosclerosis , Cálculos Renales , Encuestas Nutricionales , Humanos , Masculino , Femenino , Estudios Transversales , Adulto , Cálculos Renales/epidemiología , Cálculos Renales/sangre , Persona de Mediana Edad , Prevalencia , Aterosclerosis/epidemiología , Aterosclerosis/sangre , Aterosclerosis/etiología , Triglicéridos/sangre , Factores de Riesgo , Recurrencia , HDL-Colesterol/sangre , Estados Unidos/epidemiología , Modelos Logísticos

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Macroscopic self-assembly of µm-to-mm components (dimension from 100 µm to millimeters), is meaningful to realize the concept of "self-assembly at all scales" and to understand interfacial phenomena such as adhesion, self-healing, and adsorption. However, self-assembly at this length scale is different from molecular self-assembly due to limited collision chances and binding capacity between components. Long-time contact between components is requisite to realize µm-to-mm assembly. Even though the recent idea of adding a compliant coating to enhance the molecular binding capacity is effective for such self-assembly, a trade-off between coating thickness (several micrometers) and assembly efficiency exists. Here a new compliant coating of surface-initiated polymer brush to address the above paradox by both realizing fast assembly and reducing the coating thickness to ≈40 nm by two magnitudes is demonstrated. Millimeter-sized quartz cubes are used as components and grafted with oppositely charged polyelectrolyte brushes, enabling assembly in water by electrostatic attraction and disassembly in NaCl solutions. A rule of thickness-dependent assembly chance is obtained and understood by in situ force measurements and a multivalent theory. The polymer brush strategy pushes the thickness limit of requisite compliant coating to the nanoscale for fast µm-to-mm self-assembly and provides insights into rapid wet adhesion.

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Approximately 15% of patients with colorectal cancer (CRC) exhibit a distinct molecular phenotype known as microsatellite instability (MSI). Accurate and non-invasive prediction of MSI status is crucial for cost savings and guiding clinical treatment strategies. The retrospective study enrolled 307 CRC patients between January 2020 and October 2022. Preoperative images of computed tomography and postoperative status of MSI information were available for analysis. The stratified fivefold cross-validation was used to avoid sample bias in grouping. Feature extraction and model construction were performed as follows: first, inter-/intra-correlation coefficients and the least absolute shrinkage and selection operator algorithm were used to identify the most predictive feature subset. Subsequently, multiple discriminant models were constructed to explore and optimize the combination of six feature preprocessors (Box-Cox, Yeo-Johnson, Max-Abs, Min-Max, Z-score, and Quantile) and three classifiers (logistic regression, support vector machine, and random forest). Selecting the one with the highest average value of the area under the curve (AUC) in the test set as the radiomics model, and the clinical screening model and combined model were also established using the same processing steps as the radiomics model. Finally, the performances of the three models were evaluated and analyzed using decision and correction curves.We observed that the logistic regression model based on the quantile preprocessor had the highest average AUC value in the discriminant models. Additionally, tumor location, the clinical of N stage, and hypertension were identified as independent clinical predictors of MSI status. In the test set, the clinical screening model demonstrated good predictive performance, with the average AUC of 0.762 (95% confidence interval, 0.635-0.890). Furthermore, the combined model showed excellent predictive performance (AUC, 0.958; accuracy, 0.899; sensitivity, 0.929) and favorable clinical applicability and correction effects. The logistic regression model based on the quantile preprocessor exhibited excellent performance and repeatability, which may further reduce the variability of input data and improve the model performance for predicting MSI status in CRC.

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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Tomografía Computarizada por Rayos X/métodos , Adulto , Algoritmos , Máquina de Vectores de Soporte , Modelos Logísticos

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A large-scale, high-speed, long-runout landslide occurred in Xinmo Village, Maoxian, Sichuan Province, China, on June 24, 2017. It was characterized by fast sliding speed, rapid volume growth, and large impact area. The dynamic process of such landslides and the influence of erosion on the dynamic process are studied by field investigation, numerical inversion and simulation. The results showed that entrainment erosion was a major factor of landslide volumetric change and a salient feature of the landslide process. An exponential equation relating the erosion rate and the deposition volume was established. Moreover, the study found that a slight change of the erosion rate (1e-4) also had a significant impact on the lateral spreading, longitudinal runout, and vertical erosion. As the erosion rate increased, the lateral spreading, longitudinal runout, and vertical erosion of this type of landslide became more obvious. By using the coefficient of variation method, it was obtained that the erosion rate had a greater influence on the vertical erosion than on the lateral spreading and longitudinal runout. In the study of the velocity of the rock avalanche under different erosion conditions, it was found that the erosion amount and the landslide velocity were not strictly linearly related. This study has important significance for understanding the dynamic process and erosion effect of rock avalanche, and provides useful references and insights for future research in related fields.

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Tensile and low-cycle fatigue tests of high-strength compacted graphite cast iron (CGI, RuT450) were carried out at 25 °C, 400 °C, and 500 °C, respectively. The results show that with the increase in temperature, the tensile strength decreases slowly and then decreases rapidly. The fatigue life decreases, and the life reduction increases at high temperature and high strain amplitude. The oxide layer appears around the graphite and cracks at high temperature, and the dependence of crack propagation on ferrite gradually decreases. With the increase in strain amplitude, the initial cyclic stress of compacted graphite cast iron increases at three temperatures, and the cyclic hardening phenomenon is obvious. The fatigue life prediction method based on the energy method and damage mechanism for compacted graphite cast iron is summarized and proposed after comparing and analyzing a large amount of fatigue data.

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A 2-year-and-10-month-old boy presented with multiple masses in the neck and chest for over 3 months. The child had a history of unstable walking, with hard lumps visible at the injury sites after falls, which would resolve on their own. Following a recent injury, a mass was discovered in the posterior neck, protruding above the skin surface and accompanied by limited joint movement. Gradually, new masses were found on the left side of the neck, back near the scapular lower angle, in the scapular fossa, and along the left axillary midline. Magnetic resonance imaging examination showed diffuse low signal on T1-weighted images and high signal on T2-weighted images in the bilateral posterior neck and back muscles two months ago. A CT scan revealed muscle swelling, with areas of patchy low density and multiple nodular high-density ossifications within some muscles. Genetic testing results indicated a mutation in the ACVR1 gene, leading to the final diagnosis of progressive ossifying myositis in this patient. This article summarizes the etiology, diagnosis, and treatment of one case of progressive ossifying myositis, providing a reference for clinicians.

Asunto(s)

Receptores de Activinas Tipo I , Mutación , Miositis Osificante , Humanos , Masculino , Miositis Osificante/genética , Miositis Osificante/diagnóstico por imagen , Receptores de Activinas Tipo I/genética , Preescolar

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BACKGROUND: It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the 'weekend warrior' physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. METHODS: This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (< 150 min/week of MVPA), weekend warrior (≥ 150 min/week of MVPA in 1 or 2 sessions), and physically active (≥ 150 min/week of MVPA in 3 or more sessions). RESULTS: A total of 6067 participants living with type 2 diabetes [mean (SD) age, 61.4 (13.5) years; 48.0% females] were followed for a median of 6.1 years, during which 1206 deaths were recorded. Of leisure-time and occupational activity, compared with inactive individuals, hazard ratios (HRs) for all-cause mortality were 0.49 (95% CI 0.26-0.91) and 0.57 (95% CI 0.38-0.85) for weekend warrior individuals, and 0.55 (95% CI 0.45-0.67) and 0.64 (95% CI 0.53-0.76) for regularly active individuals, respectively. However, when compared leisure-time and occupational weekend warrior with regularly active participants, the HRs were 0.82 (95% CI 0.42-1.61) and 1.00 (95% CI 0.64-1.56) for all-cause mortality, respectively. CONCLUSIONS: Weekend warrior PA pattern may have similar effects on lowering all-cause mortality as regularly active pattern among adults living with type 2 diabetes, regardless of leisure-time or occupational activity. Therefore, weekend warrior PA pattern may be sufficient to reduce all-cause mortality for adults living with type 2 diabetes.

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The widespread implementation of low-dose computed tomography (LDCT) in lung cancer screening has led to the increasing detection of pulmonary nodules. However, precisely evaluating the malignancy risk of pulmonary nodules remains a formidable challenge. Here we propose a triage-driven Chinese Lung Nodules Reporting and Data System (C-Lung-RADS) utilizing a medical checkup cohort of 45,064 cases. The system was operated in a stepwise fashion, initially distinguishing low-, mid-, high- and extremely high-risk nodules based on their size and density. Subsequently, it progressively integrated imaging information, demographic characteristics and follow-up data to pinpoint suspicious malignant nodules and refine the risk scale. The multidimensional system achieved a state-of-the-art performance with an area under the curve (AUC) of 0.918 (95% confidence interval (CI) 0.918-0.919) on the internal testing dataset, outperforming the single-dimensional approach (AUC of 0.881, 95% CI 0.880-0.882). Moreover, C-Lung-RADS exhibited a superior sensitivity compared with Lung-RADS v2022 (87.1% versus 63.3%) in an independent cohort, which was screened using mobile computed tomography scanners to broaden screening accessibility in resource-constrained settings. With its foundation in precise risk stratification and tailored management, this system has minimized unnecessary invasive procedures for low-risk cases and recommended prompt intervention for extremely high-risk nodules to avert diagnostic delays. This approach has the potential to enhance the decision-making paradigm and facilitate a more efficient diagnosis of lung cancer during routine checkups as well as screening scenarios.

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BACKGROUND: This study aims to utilize the deep learning method of VB-Net to locate and segment the trigeminal nerve, and employ radiomics methods to distinguish between CTN patients and healthy individuals. METHODS: A total of 165 CTN patients and 175 healthy controls, matched for gender and age, were recruited. All subjects underwent magnetic resonance scans. VB-Net was used to locate and segment the bilateral trigeminal nerve of all subjects, followed by the application of radiomics methods for feature extraction, dimensionality reduction, feature selection, model construction, and model evaluation. RESULTS: On the test set for trigeminal nerve segmentation, our segmentation parameters are as follows: the mean Dice Similarity Coefficient (mDCS) is 0.74, the Average Symmetric Surface Distance (ASSD) is 0.64 mm, and the Hausdorff Distance (HD) is 3.34 mm, which are within the acceptable range. Analysis of CTN patients and healthy controls identified 12 features with larger weights, and there was a statistically significant difference in Rad_score between the two groups (p < 0.05). The Area Under the Curve (AUC) values for the three models (Gradient Boosting Decision Tree, Gaussian Process, and Random Forest) are 0.90, 0.87, and 0.86, respectively. After testing with DeLong and McNemar methods, these three models all exhibit good performance in distinguishing CTN from normal individuals. CONCLUSIONS: Radiomics can aid in the clinical diagnosis of CTN, and it is a more objective approach. It serves as a reliable neurobiological indicator for the clinical diagnosis of CTN and the assessment of changes in the trigeminal nerve in patients with CTN.

Asunto(s)

Aprendizaje Profundo , Imagen por Resonancia Magnética , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/diagnóstico por imagen , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Estudios de Casos y Controles , Adulto , Anciano , Nervio Trigémino/diagnóstico por imagen , Radiómica

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OBJECTIVE: The objective of this study is to investigate the presence of astrocyte antibodies in patients, excluding aquaporin-4 or glial fibrillary acidic protein (GFAP) antibodies, while evaluating associated biomarkers and pathologies. METHODS: Patient serum and cerebrospinal fluid (CSF) were tested for antibodies using tissue- and cell-based assays. Neurofilament light chain (NFL) and GFAP in the CSF were detected using single-molecule array (SIMOA). RESULTS: 116 patients accepted SIMOA. Fifteen functional neurological disorders patients without antibodies were designated as controls. Thirty-five patients were positive for astrocyte antibodies (Anti-GFAP: 7; Anti-AQP4: 7; unknown antibodies: 21, designed as the double-negative group, DNAP). The most frequent phenotype of DNAP was encephalitis (42.9%), followed by myelitis (23.8%), movement disorders (19.0%), and amyotrophic lateral sclerosis-like (ALS-like) disease (14.2%). The levels of CSF GFAP and NFL in DNAP were higher than in the control (GFAP: 1967.29 [776.60-13214.47] vs 475.38 [16.80-943.60] pg/mL, p < 0.001; NFL: 549.11 [162.08-2462.61] vs 214.18 [81.60-349.60] pg/mL, p = 0.002). GFAP levels decreased in DNAP (n = 5) after immunotherapy (2446.75 [1583.45-6277.33] vs 1380.46 [272.16-2005.80] pg/mL, p = 0.043), while there was no difference in NFL levels (2273.78 [162.08-2462.61] vs 890.42 [645.06-3168.06] pg/mL, p = 0.893). Two brain biopsy patterns were observed: one exhibited prominent tissue proliferation and hypertrophic astrocytes, with local loss of astrocytes, while the other showed severe astrocyte depletion with loss of neurofilaments around the vessels. Eighteen patients received immunotherapy, and improved except one with ALS-like symptoms. We identified anti-vimentin in this patient. DISCUSSION: There are unidentified astrocyte antibodies. The manifestations of double-negativity are heterogeneous; nevertheless, the pathology and biomarkers remain consistent with astrocytopathy. Immunotherapy is effective.

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Acuaporina 4 , Astrocitos , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Inmunoglobulina G , Humanos , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/inmunología , Femenino , Masculino , Acuaporina 4/inmunología , Persona de Mediana Edad , Astrocitos/inmunología , Astrocitos/metabolismo , Astrocitos/patología , Estudios Retrospectivos , Adulto , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Anciano , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Proteínas de Neurofilamentos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Adulto Joven , Adolescente

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Emerging evidence shows that psychological stress promotes the progression of Parkinson's disease (PD) and the onset of dyskinesia in non-PD individuals, highlighting a potential avenue for therapeutic intervention. We previously reported that chronic restraint-induced psychological stress precipitated the onset of parkinsonism in 10-month-old transgenic mice expressing mutant human α-synuclein (αSyn) (hαSyn A53T). We refer to these as chronic stress-genetic susceptibility (CSGS) PD model mice. In this study we investigated whether ginsenoside Rg1, a principal compound in ginseng notable for soothing the mind, could alleviate PD deterioration induced by psychological stress. Ten-month-old transgenic hαSyn A53T mice were subjected to 4 weeks' restraint stress to simulate chronic stress conditions that worsen PD, meanwhile the mice were treated with Rg1 (40 mg· kg-1 ·d-1, i.g.), and followed by functional magnetic resonance imaging (fMRI) and a variety of neurobehavioral tests. We showed that treatment with Rg1 significantly alleviated both motor and non-motor symptoms associated with PD. Functional MRI revealed that Rg1 treatment enhanced connectivity between brain regions implicated in PD, and in vivo multi-channel electrophysiological assay showed improvements in dyskinesia-related electrical activity. In addition, Rg1 treatment significantly attenuated the degeneration of dopaminergic neurons and reduced the pathological aggregation of αSyn in the striatum and SNc. We revealed that Rg1 treatment selectively reduced the level of the stress-sensitive protein RTP801 in SNc under chronic stress conditions, without impacting the acute stress response. HPLC-MS/MS analysis coupled with site-directed mutation showed that Rg1 promoted the ubiquitination and subsequent degradation of RTP801 at residues K188 and K218, a process mediated by the Parkin RING2 domain. Utilizing αSyn A53T+; RTP801-/- mice, we confirmed the critical role of RTP801 in stress-aggravated PD and its necessity for Rg1's protective effects. Moreover, Rg1 alleviated obstacles in αSyn autophagic degradation by ameliorating the RTP801-TXNIP-mediated deficiency of ATP13A2. Collectively, our results suggest that ginsenoside Rg1 holds promise as a therapeutic choice for treating PD-sensitive individuals who especially experience high levels of stress and self-imposed expectations.

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The inherent metal elements and structures of Prussian blue analogue (PBA) nanozymes have restricted their enzyme-mimicking activity. Therefore, the rational regulation of PBA nanozymes to improve their catalytic activity is highly desirable for biosensing applications. Herein, we propose a structure remodeling strategy to construct an open-cage Fe PBA-anchored NiFePBA (NiFe@Fe bis-PBA) nanozyme with significantly enhanced enzyme-mimicking activity. The formation process and mechanism for this bis-PBA nanozyme were studied in detail. Specifically, a cubic NiFePBA precursor was first synthesized and modified with polyvinylpyrrolidone (PVP). With the aid of hydrochloric acid, the added potassium ferricyanide was reduced by PVP and re-coordinated on the surface of NiFePBA to form the NiFe@Fe bis-PBA nanozyme with a special open-cage core-shell structure. The resultant NiFe@Fe bis-PBA nanozyme was further exploited to immobilize secondary antibodies, serving as a novel signal probe for developing highly sensitive electrochemical immunosensors for monitoring tumor markers. The constructed electrochemical immunosensor possesses a very wide linear range of 0.005-100 ng/mL and a low detection limit of 0.89 pg/mL for alpha-fetoprotein with high specificity and acceptable reproducibility and stability. This work offers a general and promising strategy for remodeling PBA nanozymes with a very favorable structure and metal element distribution, which enhances their enzyme-mimicking properties for applications in different fields.

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Soil salinization is one of the major factors limiting agricultural production. Utilizing beneficial microorganisms like Piriformospora indica (P. indica) to enhance plant tolerance to abiotic stresses is a highly effective method, but the influence of P. indica on the growth of soybean in natural saline-alkaline soil remains unclear. Therefore, we investigated the effects of non-inoculation, P. indica inoculation, and fertilization on the growth, antioxidant defense, osmotic adjustment, and photosynthetic gas exchange parameters of soybean under two different levels of saline-alkaline stress in non-sterilized natural saline-alkaline soil. The study found that: 1) P. indica inoculation significantly promoted soybean growth, increasing plant height, root length, and biomass. Under mildly saline-alkaline stress, the increases were 11.5%, 16.0%, and 14.8%, respectively, compared to non-inoculated treatment. Under higher stress, P. indica inoculation achieved the same level of biomass increase as fertilization, while fertilization only significantly improved stem diameter. 2) Under saline-alkaline stress, P. indica inoculation significantly increased antioxidant enzyme activities and reduced malondialdehyde (MDA) content. Under mildly stress, MDA content was reduced by 47.1% and 43.3% compared to non-inoculated and fertilized treatments, respectively. Under moderate stress, the MDA content in the inoculated group was reduced by 29.9% and 36.6% compared to non-inoculated and fertilized treatments, respectively. Fertilization only had a positive effect on peroxidase (POD) activity. 3) P. indica inoculation induced plants to produce more osmotic adjustment substances. Under mildly stress, proline, soluble sugars, and soluble proteins were increased by 345.7%, 104.4%, and 6.9%, respectively, compared to non-inoculated treatment. Under higher stress, the increases were 75.4%, 179.7%, and 12.6%, respectively. Fertilization had no significant positive effect on proline content. 4) With increasing stress, soybean photosynthetic capacity in the P. indica-inoculated treatment was significantly higher than in the non-inoculated treatment, with net photosynthetic rate increased by 14.8% and 37.0% under different stress levels. These results indicate that P. indica can enhance soybean's adaptive ability to saline-alkaline stress by regulating ROS scavenging capacity, osmotic adjustment substance content, and photosynthetic capacity, thereby promoting plant growth. This suggests that P. indica has great potential in improving soybean productivity in natural saline-alkaline soils.

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BACKGROUND: Whether endobiliary radiofrequency ablation (EB-RFA) changes the standard role of stent placement in treating unresectable malignant biliary obstruction (MBO) remains unclear. The aim of this study is to compare percutaneous EB-RFA and metal stent placement (RFA-Stent) with metal stent placement alone (Stent) in treating unresectable MBO using a propensity score matching (PSM) analysis. METHODS: From June 2013 to June 2018, clinical data from 163 patients with malignant biliary obstruction who underwent percutaneous RFA-Stent or stenting alone were retrospectively analyzed using a nearest-neighbor algorithm to one-to-one PSM analysis to compare primary and secondary stent patency (PSP, SSP), overall survival (OS) and complications between the two groups. RESULTS: Before matching, for whole patients, RFA-Stent resulted in longer median PSP (8.0 vs. 5.1 months, P = 0.003), SSP (9.8 vs. 5.1 months, P < 0.001) and OS (7.0 vs. 4.5 months, P = 0.034) than the Stent group. After matching (54 pairs), RFA-Stent also resulted in better median PSP (8.5 vs. 5.1 months, P < 0.001), SSP (11.0 vs. 6.0 months, P < 0.001), and OS (8.0 vs. 4.0 months, P = 0.007) than Stent. RFA-Stent was comparable with Stent for complication rates. In Cox analysis, RFA-Stent modality and serum total bilirubin level were independent prognostic factors for PSP. RFA-Stent modality, performance status score and combination therapy after stent were independent prognostic factors for OS. CONCLUSION: Percutaneous RFA-Stent was superior to Stent in terms of PSP, SSP, and OS in selected patients with unresectable MBO.

Asunto(s)

Colestasis , Puntaje de Propensión , Ablación por Radiofrecuencia , Stents , Humanos , Estudios Retrospectivos , Masculino , Femenino , Anciano , Colestasis/etiología , Colestasis/cirugía , Ablación por Radiofrecuencia/métodos , Persona de Mediana Edad , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Resultado del Tratamiento , Anciano de 80 o más Años

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Esculetin (ESC) is a coumarin-derived phytochemical prevalent in traditional Chinese medicine that exhibits anti-acute ischemic stroke activities. Our previous studies demonstrate that CKLF1 is a potential anti-stroke target for coumarin-derived compound. In this study we investigated whether CKLF1 was involved in the neuroprotective effects of ESC against photothrombotic stroke in mice. The mice were treated with ESC (20, 40 or 80 mg·kg-1·d-1, i.g.) for two weeks. The therapeutic effect of ESC was assessed using MRI, neurological function evaluation, and a range of behavioral tests on D1, 3, 7 and 14 of ESC administration. We showed that oral administration of ESC dose-dependently reduced the cerebral infarction volume within one week after stroke, improved behavioral performance, and alleviated neuropathological damage within two weeks. Functional MRI revealed that ESC significantly enhanced the abnormal low-frequency fluctuation (ALFF) value of the motor cortex and promoted functional connectivity between the supplementary motor area (SMA) and multiple brain regions. We demonstrated that ESC significantly reduced the protein levels of CKLF1 and CCR5, as well as the CKLF1/CCR5 protein complex in the peri-infarcted area. We showed that ESC (0.1-10 µM) dose-dependently blocked CKLF1-induced chemotactic movement of neutrophils in the Transwell assay, reducing the interaction of CKLF1/CCR5 on the surface of neutrophils, thereby reducing neutrophil infiltration, and decreasing the expression of ICAM-1, VCAM-1 and MMP-9 in the peri-infarct tissue. Knockout of CKLF1 reduced brain infarction volume and motor dysfunction after stroke but also negated the anti-stroke efficacy and neutrophil infiltration of ESC. These results suggest that the efficacy of ESC in promoting post-stroke neural repair depends on its inhibition on CKLF1-mediated neutrophil infiltration, which offering novel perspectives for elucidating the therapeutic properties of coumarins.

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Glioma is the most common brain tumor, accounting for a large majority of cancer-related deaths. ß-galactoside α2, 6 sialyltranferase 1 (ST6Gal1), the primary enzyme responsible for the conjugation of α2, 6 sialic acids to protein and lipid targets, is strongly associated with the occurrence and development of several brain tumor types. Still, the expression, targets, and functions of ST6Gal1 in glioma patients remain undetermined. As sialylation of the Ig-like cell adhesion family molecules have prominent roles in the latter's regulation in other biological contexts, we screened for members that have potential to be regulated by ST6Gal1 in silico and examined co-expressed protein modules using data derived from the Cancer Genome Atlas (TCGA) database, and we identified neural cell adhesion molecule (NCAM1) as a major ST6Gal1-interacting target. Bioinformatic binding analysis confirmed the interaction of ST6Gal1 and NCAM1. Immunohistochemistry was then used to evaluate post-operative samples from 156 patients with gliomas. ST6Gal1 and NCAM1 were co-expressed in gliomas, and their expression correlated significantly (p = 0.002) by univariate analysis. Our study also found that the expression levels of both ST6Gal1 and NCAM1 corresponded negatively with glioma grade, isocitrate dehydrogenase (IDH) mutation, and proliferation index (Ki67). Consistently, Kaplan-Meier survival curves showed that lower ST6Gal1 and NCAM1 protein levels are linked to unfavorable outcomes in glioma patients (p = 0.018 and p < 0.001, respectively). Our data indicate that ST6Gal1 may participate in the inhibition of oncogenesis and malignant progression via interacting with and targeting NCAM1 in glioma, thus presenting a novel strategy for intervention.

Asunto(s)

Neoplasias Encefálicas , Glioma , Sialiltransferasas , Humanos , Glioma/patología , Glioma/genética , Glioma/metabolismo , Sialiltransferasas/genética , Sialiltransferasas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Masculino , Femenino , Adulto , Persona de Mediana Edad , Antígenos CD/metabolismo , Antígeno CD56/metabolismo , Anciano , Biomarcadores de Tumor/metabolismo , beta-D-Galactósido alfa 2-6-Sialiltransferasa

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Mycoplasma bovis (M. bovis) is capable of causing a range of diseases in cattle, encompassing calf pneumonia, arthritis, conjunctivitis, meningitis, and mastitis. It is widely recognized as one of the predominant pathogens posing a significant threat to the global cattle industry. Therefore, accurate and sensitive methods are urgently needed to detect M. bovis. This study aims to detect M. bovis by combining colloidal gold with biotin-labeled oligonucleotides to improve detection sensitivity and form a chromogenic detection probe based on signal amplification technology. Here, we developed a sensitive and specific polymerase chain reaction-lateral flow dipstick assay (PCR-LFD) strip for efficient nucleic acid detection of M. bovis. A pair of specific primers with 5' ends labeled with biotin and digoxigenin probes was designed for PCR experiments. Colloidal gold particles-labeled anti-digoxigenin IgG coated gold-labeled test strip was prepared, streptavidin was used as the detection probe, and nitrocellulose membrane coated goat anti-mouse IgG was used as the control line. Our results showed that the detection limit of the PCR-LFD was 89 fg/µL for the M. bovis DNA. The results from the test strip were highly consistent with those from real-time qPCR. This assay were highly specific for M. bovis, as there were no cross-reactions with other microorganisms tested and the detection sensitivity of the test was also relatively high (97.67%). The novel strips present a promising tool for the cost-effective and sensitive diagnosis of M. bovis.

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Enfermedades de los Bovinos , Infecciones por Mycoplasma , Mycoplasma bovis , Reacción en Cadena de la Polimerasa , Sensibilidad y Especificidad , Animales , Mycoplasma bovis/aislamiento & purificación , Mycoplasma bovis/genética , Bovinos , Enfermedades de los Bovinos/diagnóstico , Enfermedades de los Bovinos/microbiología , Infecciones por Mycoplasma/veterinaria , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/microbiología , Reacción en Cadena de la Polimerasa/veterinaria , Reacción en Cadena de la Polimerasa/métodos , ADN Bacteriano/análisis , Oro Coloide/química

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Developing an effective method to stably enhance the quantum efficiency (QE) and extend the photoemission threshold of Cu photocathodes beyond the ultraviolet region could benefit the photoinjector for ultrafast electron source applications. The implementation of a 2D material protective layer is considered a promising approach to extending the operating lifetime of photocathodes. We propose that graphene can serve as an intermediate layer at the interface between photocathode material and low-work-function coating. The role of oxygen in the Cs/O activation process on the Cu surface is altered by the graphene interlayer. Besides, the few-layer graphene (FLG) surface could be more likely to induce the formation of Cs2O. Thus, the graphene-Cu composite photocathode can achieve an ultralow surface work function of down to 0.878 eV through Cs/O activation. The photoemission performance of the composite cathode with a FLG interlayer is significantly enhanced. The photocathode has an extended spectral response to the near-infrared region and a higher QE. At 350 nm, its QE is more than twice that of the cesiated bare Cu, reaching 0.247%. After degradation, the graphene-Cu cathode can be fully restored by reactivation, with remarkably enhanced stability. In addition, the composite cathode can be operated reliably under a poor vacuum pressure of over 4 × 10-6 Pa. This study validates a new method for incorporating 2D materials into photocathodes, offering novel approaches to explore robust and spectrum-extended photocathodes.

RESUMEN

X-linked severe combined immunodeficiency (X-SCID), caused by mutations in the gamma-chain gene of the interleukin-2 receptor (IL2RG), is a prevalent form of SCID characterized by recurrent and fatal opportunistic infections that occur early in life. The incidence of disseminated bacillus Calmette-Guérin (BCG) disease among children with SCID is much higher than in the general population. Here, we report the case of a 4-month-old male infant who presented with subcutaneous induration, fever, an unhealed BCG vaccination site, and hepatosplenomegaly. Metagenomic next-generation sequencing in blood, and the detection of gastric juice and skin nodule pus all confirmed the infection of Mycobacterium tuberculosis. Lymphocyte subset analysis confirmed the presence of T-B+NK immunodeficiency. Whole-exome and Sanger sequencing revealed a novel microdeletion insertion mutation (c.316_318delinsGTGAT p.Leu106ValfsTer42) in the IL2RG gene, resulting in a rare shift in the amino acid sequence of the coding protein. Consequently, the child was diagnosed with X-SCID caused by a novel mutation in IL2RG, complicated by systemic disseminated BCG disease. Despite receiving systemic anti-infection treatment and four days of hospitalization, the patient died three days after discharge. To the best of our knowledge, this specific IL2RG mutation has not been previously reported. In our systemic review, we outline the efficacy of systemic anti-tuberculosis therapy, hematopoietic stem cell transplantation, and gene therapy in children with SCID and BCG diseases caused by IL2RG gene mutation.

Asunto(s)

Subunidad gamma Común de Receptores de Interleucina , Tuberculosis , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X , Humanos , Lactante , Masculino , Vacuna BCG/administración & dosificación , Vacuna BCG/efectos adversos , Vacuna BCG/inmunología , Exones , Subunidad gamma Común de Receptores de Interleucina/genética , Mutación , Mycobacterium bovis/inmunología , Mycobacterium bovis/patogenicidad , Tuberculosis/inmunología , Tuberculosis/prevención & control , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/complicaciones , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/diagnóstico , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/inmunología

RESUMEN

RATIONALE AND OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm affecting the kidney, exhibiting a dismal prognosis in metastatic instances. Elucidating the composition of ccRCC holds promise for the discovery of highly sensitive biomarkers. Our objective was to utilize habitat imaging techniques and integrate multimodal data to precisely predict the risk of metastasis, ultimately enabling early intervention and enhancing patient survival rates. MATERIAL AND METHODS: A retrospective analysis was performed on a cohort of 263 patients with ccRCC from three hospitals between April 2013 and March 2021. Preoperative CT images, ultrasound images, and clinical data were comprehensively analyzed. Patients from two campuses of Qilu Hospital of Shandong University were assigned to the training dataset, while the third hospital served as the independent testing dataset. A robust consensus clustering method was used to classify the primary tumor space into distinct sub-regions (i.e., habitats) using contrast-enhanced CT images. Radiomic features were extracted from these tumor sub-regions and subsequently reduced to identify meaningful features for constructing a predictive model for ccRCC metastasis risk assessment. In addition, the potential value of radiomics in predicting ccRCC metastasis risk was explored by integrating ultrasound image features and clinical data to construct and compare alternative models. RESULTS: In this study, we performed k-means clustering within the tumor region to generate three distinct tumor subregions. We quantified the Hounsfiled Unit (HU) value, volume fraction, and distribution of high- and low-risk groups in each subregion. Our investigation focused on 252 patients with Habitat1 + Habitat3 to assess the discriminative power of these two subregions. We then developed a risk prediction model for ccRCC metastasis risk classification based on radiomic features extracted from CT and ultrasound images, and clinical data. The Combined model and the CT_Habitat3 model showed AUC values of 0.935 [95%CI: 0.902-0.968] and 0.934 [95%CI: 0.902-0.966], respectively, in the training dataset, while in the independent testing dataset, they achieved AUC values of 0.891 [95%CI: 0.794-0.988] and 0.903 [95%CI: 0.819-0.987], respectively. CONCLUSION: We have identified a non-invasive imaging predictor and the proposed sub-regional radiomics model can accurately predict the risk of metastasis in ccRCC. This predictive tool has potential for clinical application to refine individualized treatment strategies for patients with ccRCC.