A Nomogram Including Sarcopenia for Predicting Progression-Free Survival in Patients with Localized Papillary Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. METHODS: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. RESULTS: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03-0.66), SAT (HR 6.36, 95% CI 2.39-16.93), PRAT (HR 4.66, 95% CI 1.77-12.27), tumor diameter (HR 0.35, 95% CI 0.14-0.86), and surgical technique (HR 2.85, 95% CI 1.06-7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761-0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. CONCLUSIONS: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future.

Small Molecule Targeting PPM1A Activates Autophagy for Mycobacterium tuberculosis Host-Directed Therapy.

Mycobacterium tuberculosis (Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify SMIP-30, targeting PPM1A (IC50 = 1.19 µM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. SMIP-30 restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned SMIP-30 to create SMIP-031, which is a more potent inhibitor for PPM1A (IC50 = 180 nM). SMIP-031 efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. SMIP-031 possesses a good pharmacokinetic profile and oral bioavailability (F = 74%). In vivo, SMIP-031 is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.

The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway.

OBJECTIVES: Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms. METHODS: Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing. RESULTS: AS-IV decreased the levels of TNF-α, IL-6, and IL-1ß in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria. CONCLUSION: AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.

Increased Functional Connectivity Between the Parietal and Occipital Modules Among Flight Cadets.

INTRODUCTION: Modular organization in brain regions often performs specific biological functions and is largely based on anatomically and/or functionally related brain areas. The current study aimed to explore changes in whole-brain modular organization affected by flight training.METHODS: The study included 25 male flight cadets and 24 male controls. The first assessment was performed in 2019, when the subjects were university freshmen. The second assessment was completed in 2022. High spatial resolution structural imaging (T1) and resting-state functional MRI data were collected. Then, 90 cerebral regions were organized into 6 brain modules. The intensity of intra- and intermodular communication was calculated.RESULTS: Mixed-effect regression model analysis identified significantly increased interconnections between the parietal and occipital modules in the cadet group, but significantly decreased interconnections in the control group. This change was largely attributed to flight training.DISCUSSION: Pilots need to control the aircraft (e.g., attitude, heading, etc.) using the stick and pedal in response to the current state of the aircraft displayed by the instrument panel; as such, flying requires a large amount of hand-eye coordination. Day-to-day flight training appeared to intensify the connection between the parietal and occipital modules among cadets.Chen X, Jiang H, Meng Y, Xu Z, Luo C. Increased functional connectivity between the parietal and occipital modules among flight cadets. Aerosp Med Hum Perform. 2024; 95(7):375-380.

Characterization and noncovalent inhibition of the K63-deubiquitinase activity of SARS-cov-2 PLpro.

SARS-CoV-2 papain-like protease (PLpro) could facilitate viral replication and host immune evasion by respectively hydrolyzing viral polyprotein and host ubiquitin conjugates, thereby rendering itself as an important antiviral target. Yet few noncovalent PLpro inhibitors of SARS-CoV-2 have been reported with improved directed towards pathogenic deubiquitinating activities inhibition. Herein, we report that coronavirus PLpro proteases have distinctive substrate bias and are conserved to deubiquitylate K63-linked polyubiquitination, thereby attenuating host type I interferon response. We identify a noncovalent compound specifically optimized towards halting the K63-deubiquitinase activity of SARS-CoV-2 PLpro, but not other coronavirus (CoV) counterparts or host deubiquitinase. Contrasting with GRL-0617, a SARS-CoV-1 PLpro inhibitor, SIMM-036 is 50-fold and 7-fold (half maximal inhibitory concentration (IC50)) more potent to inhibit viral replication during SARS-CoV-2 infection and restore the host interferon-ß (IFN-ß) response in human angiotensin-converting enzyme 2 (hACE2)-HeLa cells, respectively. Structure-activity relationship (SAR) analysis further reveals the importance of BL2 groove of PLpro, which could determine the selectivity of K63-deubiquitinase activity of the enzyme.

Intraventricular Thrombosis and Pulmonary Embolism Post-Nuss Procedure: A Rare Case of Chronic Bar Displacement in a 16-Year-Old Patient.

This novel report presents the first known case, to our knowledge, of a 16-year-old male patient who experienced intraventricular thrombosis and pulmonary embolism after a Nuss procedure for pectus excavatum, attributed to chronic bar displacement. Two years after the operation, the patient experienced post-exercise cough and hemoptysis, which led to his admission. Imaging revealed pulmonary embolism, thrombosis in the right ventricular outflow tract, and lung infiltrative lesions. We hypothesize that the chronic bar displacement led to its embedment in the right ventricle, resulting in thrombus formation, which subsequently contributed to partial pulmonary embolism. Surgery revealed the bars' intrusion into the right ventricle and lung. This case highlights the risk of severe complications from bar displacement in the Nuss procedure, which necessitates long-term follow-up evaluation, caution against strenuous activities after surgery, and use of thoracoscopic guidance during bar implantation and removal. It underscores the importance of vigilant evaluation for late-stage complications in patients with respiratory distress or thrombosis after a Nuss procedure.

The impact of renovation on the air quality in the stadium, and prevention of indoor air pollution.

Indoor air quality is a critical factor influencing athletic performance, particularly in professional sports settings, yet its impact remains underexplored. This study utilizes a panel dataset from 2516 Chinese Basketball Association (CBA) matches across 20 cities in China between 2014 and 2019. We integrate daily air pollution metrics with player efficiency ratings (PER) to investigate the effects of air quality on individual performance. We find that a 10% increase in the air quality index (AQI) corresponds to a 1.4223 decrease in PER, indicating a strong negative effect of poor air quality on player productivity. Different pollutants have varying effects, with some exacerbating the decline in both overall performance and precision in tasks. Notably, older players and international players exhibit greater resilience to air pollution. These insights contribute to the development of a comprehensive index for assessing work efficiency under varying air quality conditions and suggest targeted strategies to mitigate the negative impacts of air pollution in competitive athletic settings.

Anatomical Study of the Superior Auricular Artery Using 3-Dimensional Computed Tomography Angiography.

BACKGROUND: The superior auricular artery (SAA)-retroauricular flap is commonly used for the repair of defects of the superior auricle. There are few studies about the anatomy of the SAA. OBJECTIVE: This study mainly analyzed the anatomical pattern of SAA. MATERIALS AND METHODS: Computed tomography (CT) was performed on 26 cadaver heads infused with lead oxide. The anatomical pattern of the SAA was statistically analyzed by 3-dimensional CT images. RESULTS: The SAA was classified into 3 types according to whether it gave off the helix branch or the auricular dorsal branch. The SAA was located mainly in an area 2 cm above and below the horizontal line at the midpoint of the 2 base points (the otobasion superius and the apex of the external auditory canal). The origin of each branch of the SAA was mainly located in Areas 2, 3, and 4 within a circular area that had the otobasion superius as the center of the circle and a radius of 2 cm. CONCLUSION: In this study, the 3 anatomical types and anatomical patterns of the SAA were identified. These findings can provide a reference for the design of SAA-retroauricular flaps and for surgical planning.

Enzyme-free and rapid colorimetric analysis of osteopontin via triple-helix aptamer probe coupled with catalytic hairpin assembly reaction.

BACKGROUND: Osteopontin (OPN) is closely associated with tumorigenesis, growth, invasion, and immune escape and it serves as a plasma biomarker for hepatocellular carcinoma (HCC). Nevertheless, the accurate and rapid detection of low-abundance OPN still poses significant challenges. Currently, the majority of protein detection methods rely heavily on large precision instruments or involve complex procedures. Therefore, developing a simple, enzyme-free, rapid colorimetric analysis method with high sensitivity is imperative. RESULTS: In this study, we have developed a portable colorimetric biosensor by integrating the triple-helix aptamer probe (THAP) and catalytic hairpin assembly (CHA) strategy, named as T-CHA. After binding to the OPN, the trigger probe can be released from THAP, then initiates the CHA reaction and outputs the signal through the formation of a G-quadruplex/Hemin DNAzyme with horseradish peroxidase-like activity. Consequently, this colorimetric sensor achieves visual free-labeled detection without additional fluorophore modification and allows for accurate quantification by measuring the optical density of the solution at 650 nm. Under optimal conditions, the logarithmic values of various OPN concentrations exhibit satisfactory linearity in the range of 5 pg mL-1 to 5 ng mL-1, with a detection limit of 2.04 pg mL-1. Compared with the widely used ELISA strategy, the proposed T-CHA strategy is rapid (∼105 min), highly sensitive, and cost-effective. SIGNIFICANCE: The T-CHA strategy, leveraging the low background leakage of THAP and the high catalytic efficiency of CHA, has been successfully applied to the detection of OPN in plasma, demonstrating significant promise for the early diagnosis of HCC in point-of-care testing. Given the programmability of DNA and the universality of T-CHA, it can be readily modified for analyzing other useful tumor biomarkers.

Three-Dimensional Location of the Facial Artery in Relation to the Nasolabial Fold in Asian People: A Cadaveric CTA Study.

BACKGROUND: Injection cosmetics have become popular in recent years. The nasolabial fold is one of the most important and dangerous regions in the midface, and its three-dimensional relationship with the facial artery remains unclear. METHODS: Fifty-two cadavers infused with lead oxide contrast medium via the external carotid arteries were scanned by computed tomography (CT). The three-dimensional model was reconstructed using Mimics and Origin software, and the relevant data were calculated using validated algorithms. RESULTS: There were three facial artery types according to its course in relation to the nasolabial fold. In the most common type, accounting for 83.7% of specimens, the facial artery evolves into an angular artery, with a horizontal distance between facial artery and nasolabial fold of - 1.90 ± 2.40, - 3.90 ± 2.95, - 5.18 ± 3.42, - 5.59 ± 3.53, - 5.59 ± 3.83, - 6.07 ± 4.10, - 6.92 ± 3.70, - 6.79 ± 3.37, - 4.52 ± 3.20, and - 2.76 ± 3.60 (mm) from the nasal ala to the oral commissure and a vertical distance of - 4.03 ± 2.56, - 3.27 ± 2.27, - 2.81 ± 2.57, - 2.1 ± 2.64, - 1.5 ± 3.32, - 0.71 ± 3.99, 0.92 ± 4.43, 0.4 ± 5.31, - 4.14 ± 5.14, - 7.05 ± 4.74 (mm). CONCLUSIONS: The facial artery is vulnerable to damage when injecting filler in the nasolabial fold. For the upper 1/3 of the nasolabial fold, the supraperiosteal layer is recommended for injection, while for the lower 2/3 of the nasolabial fold, the dermal layer along the nasolabial fold is recommended. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Target Identification and Mechanistic Characterization of Indole Terpenoid Mimics: Proper Spindle Microtubule Assembly Is Essential for Cdh1-Mediated Proteolysis of CENP-A.

Centromere protein A (CENP-A), a histone H3 variant specific to centromeres, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure-activity relationship (SAR) study of the cell-cycle-arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)-6-Br-JP18 and (+)-6-Cl-JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X-ray crystallography analysis reveals that both molecules bind to the colchicine-binding site of ß-tubulin. Treatment of human cells with microtubule-targeting agents (MTAs), including these two compounds, results in CENP-A accumulation by destabilizing Cdh1, a co-activator of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP-A accumulation using small-molecule tools and highlights the role of Cdh1 in CENP-A proteolysis.

Neuroimaging epicenters as potential sites of onset of the neuroanatomical pathology in schizophrenia.

Schizophrenia lacks a clear definition at the neuroanatomical level, capturing the sites of origin and progress of this disorder. Using a network-theory approach called epicenter mapping on cross-sectional magnetic resonance imaging from 1124 individuals with schizophrenia, we identified the most likely "source of origin" of the structural pathology. Our results suggest that the Broca's area and adjacent frontoinsular cortex may be the epicenters of neuroanatomical pathophysiology in schizophrenia. These epicenters can predict an individual's response to treatment for psychosis. In addition, cross-diagnostic similarities based on epicenter mapping over of 4000 individuals diagnosed with neurological, neurodevelopmental, or psychiatric disorders appear to be limited. When present, these similarities are restricted to bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. We provide a comprehensive framework linking schizophrenia-specific epicenters to multiple levels of neurobiology, including cognitive processes, neurotransmitter receptors and transporters, and human brain gene expression. Epicenter mapping may be a reliable tool for identifying the potential onset sites of neural pathophysiology in schizophrenia.

Targeting 5-Hydroxytryptamine receptor 1A in portal vein to decrease portal hypertension.

BACKGROUNDS & AIMS: Portal hypertension (PH) is one of the most frequent complications of chronic liver disease. The peripheral 5-Hydroxytryptamine (5-HT) level was increased in cirrhotic patients. We aimed to elucidate the function and mechanism of 5-HT receptor 1A (HTR1A) in portal vein (PV) on PH. METHODS: PH models were induced by thioacetamide (TAA) injection, bile duct ligation (BDL) or partial portal vein ligation (PPVL). HTR1A expression was detected using real-time PCR, in situ hybridization and immunofluorescence staining. In situ intraportal infusion was employed to assess the effects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1A antagonist WAY-100635 on portal pressure (PP). Htr1a knock-out (Htr1a-/-) rats and vascular smooth muscle cell (VSMC)-specific Htr1a knock-out (Htr1aΔVSMC) mice were utilized to confirm the regulatory role of HTR1A on PP. RESULTS: HTR1A expression was significantly increased in the hypertensive PV of PH model rats and cirrhotic patients. Additionally, 8-OH-DPAT increased but WAY-100635 decreased PP in rats, without affecting liver fibrosis and systemic hemodynamics. Furthermore, 5-HT or 8-OH-DPAT directly induced the contraction of isolated PVs. Genetic deletion of Htr1a in rats and VSMCs-specific Htr1a knock-out in mice prevented the development of PH. Moreover, 5-HT triggered the cAMP pathway-mediated PVSMCs contraction via HTR1A in PV. We also confirmed alverine as an HTR1A antagonist and demonstrated its capacity to decrease PP in TAA-, BDL-, and PPVL-induced portal hypertensive rats. CONCLUSIONS: Our findings reveal that 5-HT promotes PH by inducing the contraction of PV, and identify HTR1A as a promising therapeutic target for attenuating PH. As an HTR1A antagonist, alverine is expected to become a candidate for clinical PH treatment.

Temporal Dynamic Synchronous Functional Brain Network for Schizophrenia Classification and Lateralization Analysis.

Available evidence suggests that dynamic functional connectivity can capture time-varying abnormalities in brain activity in resting-state cerebral functional magnetic resonance imaging (rs-fMRI) data and has a natural advantage in uncovering mechanisms of abnormal brain activity in schizophrenia (SZ) patients. Hence, an advanced dynamic brain network analysis model called the temporal brain category graph convolutional network (Temporal-BCGCN) was employed. Firstly, a unique dynamic brain network analysis module, DSF-BrainNet, was designed to construct dynamic synchronization features. Subsequently, a revolutionary graph convolution method, TemporalConv, was proposed based on the synchronous temporal properties of features. Finally, the first modular test tool for abnormal hemispherical lateralization in deep learning based on rs-fMRI data, named CategoryPool, was proposed. This study was validated on COBRE and UCLA datasets and achieved 83.62% and 89.71% average accuracies, respectively, outperforming the baseline model and other state-of-the-art methods. The ablation results also demonstrate the advantages of TemporalConv over the traditional edge feature graph convolution approach and the improvement of CategoryPool over the classical graph pooling approach. Interestingly, this study showed that the lower-order perceptual system and higher-order network regions in the left hemisphere are more severely dysfunctional than in the right hemisphere in SZ, reaffirmings the importance of the left medial superior frontal gyrus in SZ. Our code was available at: https://github.com/swfen/Temporal-BCGCN.

Mechanisms insights into Cd passivation in soil by lignin biochar: Transition from flooding to natural air-drying.

Biochar shows great potential in soil cadmium pollution treatment, however, the effect and mechanisms of biochar on cadmium passivation (CP) during the long-term process of soil from flooding to natural air-drying are not clear. In this study, a 300-day experiment was conducted to keep the flooded water level constant for the first 100 days and then dried naturally. Mechanisms of CP by lignin biochar (LBC) were analyzed through chemical analysis, FTIR-2D-COS, EEMs-PARAFAC, ultraviolet spectroscopy characterizations, and microbial community distribution of soil. Results showed that application of LBC results in rapid CP ratio in soil within 35 days, mainly in the residual and Fe-Mn bound states (total 72.80%). CP ratio further increased to 90.89% with water evaporation. The CP mechanisms include precipitation, electrostatic effect, humus complexation, and microbial remediation by promoting the propagation of fungi such as Penicillium and Trichoderma. Evaporation of water promoted the colonization of aerobic microorganisms and then increased the degree of soil humification and aromatization, thereby enhancing the cadmium passivation. Simultaneously, the biochar could reduce the relative abundance of plant pathogens in soil from 1.8% to 0.03% and the freshness index (ß/α) from 0.64 to 0.16, favoring crop growth and promoting carbon sequestration and emission reduction.

Environmental risk substances in soil on seed germination: Chemical species, inhibition performance, and mechanisms.

Nowadays, numerous environmental risk substances in soil worldwide have exhibited serious germination inhibition of crop seeds, posing a threat to food supply and security. This review provides a comprehensive summary and discussion of the inhibitory effects of environmental risk substances on seed germination, encompassing heavy metals, microplastics, petroleum hydrocarbons, salinity, phenols, essential oil, agricultural waste, antibiotics, etc. The impacts of species, concentrations, and particle sizes of various environmental risk substances are critically investigated. Furthermore, three primary inhibition mechanisms of environmental risk substances are elucidated: hindering water absorption, inducing oxidative damage, and damaging seed cells/organelles/cell membranes. To address these negative impacts, diverse effective coping measures such as biochar/compost addition, biological remediation, seed priming, coating, and genetic modification are proposed. In brief, this study systematically analyzes the negative effects of environmental risk substances on seed germination, and provides a basis for the comprehensive understanding and future implementation of efficient treatments to address this significant challenge and ensure food security and human survival.

The circadian clock affects starvation resistance through the pentose phosphate pathway in silkworm, Bombyx mori.

Disruption of the circadian clock can affect starvation resistance, but the molecular mechanism is still unclear. Here, we found that starvation resistance was significantly reduced in the core gene BmPer deficient mutant silkworms (Per-/-), but the mutant's starvation resistance increased with larval age. Under natural physiological conditions, the weight of mutant 5th instar larvae was significantly increased compared to wild type, and the accumulation ability of triglycerides and glycogen in the fat bodies was upregulated. However, under starvation conditions, the weight consumption of mutant larvae was increased and cholesterol utilization was intensified. Transcriptome analysis showed that beta-oxidation was significantly upregulated under starvation conditions, fatty acid synthesis was inhibited, and the expression levels of genes related to mitochondrial function were significantly changed. Further investigations revealed that the redox balance, which is closely related to mitochondrial metabolism, was altered in the fat bodies, the antioxidant level was increased, and the pentose phosphate pathway, the source of reducing power in cells, was activated. Our findings suggest that one of the reasons for the increased energy burden observed in mutants is the need to maintain a more robust redox balance in metabolic tissues. This necessitates the diversion of more glucose into the pentose phosphate pathway to ensure an adequate supply of reducing power.

Ezrin Contributes to the Damage of Airway Epithelial Barrier Related to Diabetes Mellitus.

Background: Diabetes mellitus predisposes individuals to respiratory infections. The airway epithelial barrier provides defense against inhaled antigens and pathogens. Ezrin, is a component of the membrane-cytoskeleton that maintains the cellular morphology, intercellular adhesion, and barrier function of epithelial cells. This study aimed to explore the role of ezrin in airway epithelial barrier damage and correlate its expression and activation with diabetes mellitus. Methods: This study was performed in a murine model of diabetes mellitus and with human bronchial epithelial BEAS-2B cells using real-time PCR, Western blotting, immunohistochemical and immunofluorescence staining. Ezrin was knocked down in BEAS-2B cells using siRNA. Ezrin phosphorylation levels were measured to determine activation status. The integrity of the airway epithelial barrier was assessed in vivo by characterizing morphological structure, and in vitro in BEAS-2B cells by measuring tight junction protein expression, transepithelial electrical resistance (TER) and permeability. Results: We demonstrated that ezrin expression levels were lower in the lung tissue and airway epithelium of diabetic mice than those in control mice. The morphological structure of the airway epithelium was altered in diabetic mice. High glucose levels downregulated the expression and distribution of ezrin and connexin 43, reduced the expression of tight junction proteins, and altered the epithelial barrier characteristics of BEAS-2B cells. Ezrin knockdown had effects similar to those of high glucose levels. Moreover, a specific inhibitor of ezrin Thr567 phosphorylation (NSC305787) inhibited epithelial barrier formation. Conclusion: These results demonstrate that ezrin expression and activation are associated with airway epithelial damage in diabetes mellitus. These findings provide new insights into the molecular pathogenesis of pulmonary infections in diabetes mellitus and may lead to novel therapeutic interventions for airway epithelial barrier damage.

Develop a radiomics-based machine learning model to predict the stone-free rate post-percutaneous nephrolithotomy.

Radiomics and machine learning have been extensively utilized in the realm of urinary stones, particularly in forecasting stone treatment outcomes. The objective of this study was to integrate clinical variables and radiomic features to develop a machine learning model for predicting the stone-free rate (SFR) following percutaneous nephrolithotomy (PCNL). A total of 212 eligible patients who underwent PCNL surgery at the Second Affiliated Hospital of Nanchang University were included in a retrospective analysis. Preoperative clinical variables and non-contrast-enhanced CT images of all patients were collected, and radiomic features were extracted after delineating the stone ROI. Univariate analysis was conducted to identify clinical variables strongly correlated with the stone-free rate after PCNL, and the least absolute shrinkage and selection operator algorithm (lasso regression) was utilized to screen radiomic features. Four supervised machine learning algorithms, including Logistic Regression, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Gradient Boosting Decision Tree (GBDT), were employed. The clinical variables with strong correlation and screened radiomic features were integrated into the four machine learning algorithms to construct a prediction model, and the receiver operating curve was plotted. The area under the receiver operating curve (AUC), the accuracy rate, the specificity, etc., were used to evaluate the predictive performance of the four models. After analyzing postoperative statistics, the stone-free rate following the procedure was found to be 70.3% (n = 149). Among the various clinical variables examined, factors, such as stone number, stone diameter, stone CT value, stone location, and history of stone surgery, were identified as statistically significant in relation to the stone-free rate after PCNL. A total of 121 radiomic features were extracted, and through lasso regression, 7 features most closely associated with the stone-free rate post-PCNL were identified. The predictive accuracy of different models (Logistic Regression, RF, XGBoost, and GBDT) for determining the stone-free rate after PCNL was evaluated, yielding accuracies of 78.1%, 76.6%, 75.0%, and 73.4%, respectively. The corresponding area under the curve AUC (95%CI) were 0.85 (0.83-0.89), 0.81 (0.76-0.85), 0.82 (0.78-0.85), and 0.77 (0.73-0.81), positioning these models among the top performers in logistic regression prediction. In terms of predictive importance scores, the key factors identified by the logistic regression model were number of stone, zone percentage, stone diameter, and surface area. Similarly, the RF model highlighted number of stone, stone CT value, stone diameter, and surface area as the top predictors. Among the four machine learning models, the logistic regression model demonstrated the highest accuracy and discrimination ability in predicting the stone-free rate following PCNL. In comparison to XGBoost and GBDT, RF also exhibited superior accuracy and a certain level of discrimination ability. However, based on the performance of all four models, logistic regression is more likely to aid in clinical decision-making by assisting clinicians in diagnosing PCNL in patients. This enables us to effectively predict the presence of residual stones post-surgery and ultimately select patients who are suitable candidates for PCNL.

Analysis of the thickness characteristics of the left atrial posterior wall and its correlation with the low and no voltage areas of the left atrial posterior wall in patients with atrial fibrillation.

OBJECTIVE: To analyze the relationship between the thickness of the left atrial posterior wall and the low and no voltage zones in the left atrial posterior wall in patients with atrial fibrillation (AF). METHODS: 61 patients admitted to our cardiology department for AF and radiofrequency ablation of AF from January 1, 2020 to May 30, 2022 were enrolled according to inclusion and exclusion criteria. The atrial wall thickness was measured by CT scan. Baseline data, preoperative cardiac ultrasound data, preoperative biochemical parameters, low voltage zone (fibrotic zone) and no voltage zone (scar zone) in the left atrial posterior wall area, and various parameters of posterior left atrial wall thickness were collected. RESULTS: The differences of the thickness between the upper, middle and lower mean levels of the left atrial posterior wall were statistically significant (P = 0.004). The results showed that body mass index was weakly positively correlated with the mean level of total left atrial posterior wall thickness (r = 0.426, P = 0.001) and was statistically significant. The remaining indices were positively or negatively correlated with the mean level of total left atrial posterior wall thickness, but none were statistically significant (P > 0.05). CONCLUSIONS: Both left atrial posterior wall low-voltage zone and voltage-free zone were positively correlated with the mean total left atrial posterior wall thickness, and left atrial posterior wall low-voltage zone and voltage-free zone were significantly positively correlated. Body mass index was weakly positively correlated with total left atrial posterior wall thickness.