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Abstract Oxidative stress and inflammatory dysregulation play crucial roles in pathogenesis of acute lung injury (ALI), and their cyclic synergy drives excessive inflammatory responses and further exacerbates ALI. Therefore, new effective strategies to treat ALI are urgently needed. Herein, a novel synergistic selenium based chlorogenic acid nanoparticle was developed to disrupt the cyclic synergistic effect between oxidative stress and inflammatory response in ALI. The chlorogenic acid, a polyphenol commonly found in herb, had been effectively conjugated with human serum albumin and coated on selenium nanoparticles (Se NPs) to create CHSe NPs. The CHSe NPs exhibited superoxide dismutase(SOD) like and glutathione peroxidase(GPX) like activities, effectively scavenging various types of reactive oxygen species (ROS), and inhibited the inflammatory response of macrophages. Additionally, with excellent biosafety, CHSe NPs exhibited superior therapeutic effects in ALI mice models in vivo, surpassing the performance of the clinic drug dexamethasone. They remarkably reduced ROS levels, and elevated the SOD and GPX enzyme activities in lung tissue to exert antioxidant effects. In addition, the CHSe NPs modulated the immune microenvironment of ALI by reversing M1 macrophage polarization, downregulating the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-a), nitric oxide synthase (iNOS), and myeloperoxidase (MPO), and upregulating anti-inflammatory cytokine (IL-10) levels, thereby alleviating excessive inflammation and decreasing neutrophil infiltration. Further mechanistic research revealed that CHSe NPs directly acted on and modulated the expression of Mapk8ip1 and Itga2b, which were upstream proteins of MAPK signaling pathway and PI3K-Akt signaling pathway, therefore impeding the cyclic synergy between oxidative stress and inflammatory dysregulation. In summary, CHSe NPs synergistically exert antioxidant and anti-inflammatory effects by regulating the MAPK signaling pathway and PI3K-Akt signaling pathway, showing enormous potential in the treatment of ALI. Graphical Abstract

Abstract Accurate acne severity grading is crucial for effective clinical treatment and timely follow-up management. Although some artificial intelligence methods have been developed to automate the process of acne severity grading, the diversity of acne image capture sources and the various application scenarios can affect their performance. Therefore, it’s necessary to design special methods and evaluate them systematically before introducing them into clinical practice. To develop and evaluate a deep learning-based algorithm that could accurately accomplish acne lesion detection and severity grading simultaneously in different healthcare scenarios. We collected 2,157 facial images from two public and three self-built datasets for model development and evaluation. An algorithm called AcneDGNet was constructed with a feature extraction module, a lesion detection module and a severity grading module. Its performance was evaluated in both online and offline healthcare scenarios. Experimental results on the largest and most diverse evaluation datasets revealed that the overall performance for acne severity grading achieved accuracies of 89.5% in online scenarios and 89.8% in offline scenarios. For follow-up visits in online scenarios, the accuracy for detecting the changing trends reached 87.8%, with a total counting error of 1.91 ± 3.28 for all acne lesions. Additionally, the prospective evaluation demonstrated that AcneDGNet was not only much more accurate for acne grading than junior dermatologists but also comparable to the accuracy of senior dermatologists. These findings indicated that AcneDGNet can effectively assist dermatologists and patients in the diagnosis and management of acne, both in online and offline healthcare scenarios.

Abstract Diabetes-associated chronic skin wounds present a formidable challenge due to inadequate angiogenesis and nerve regeneration during the healing process. In the present study, we introduce a groundbreaking approach in the form of a novel cocktail therapy utilizing a multifunctional supramolecular hydrogel. Formulated through the photo-crosslinking of gelatinized aromatic residues and β-cyclodextrin (β-CD), this injectable hydrogel fosters weak host-guest interactions, offering a promising solution. The therapeutic efficacy of the hydrogel is realized through its integration with adipose-derived stem cells (ADSCs) and lipid nanoparticles encapsulating ginsenoside RG1 and Stromal cell-derived factor-1 (SDF-1). This strategic combination directs ADSCs to the injury site, guiding them toward neurogenic specialization while establishing an advantageous immunomodulatory environment through macrophage reprogramming. The synergistic effects of the newly differentiated nerve cells and the regenerative cytokines secreted by ADSCs contribute significantly to enhanced angiogenesis, ultimately expediting the diabetic wound healing process. To summarize, this innovative hydrogel-based therapeutic system represents a novel perspective for the management of diabetic wounds by concurrently targeting immune response, angiogenesis, and nerve regeneration—a pivotal advancement in the quest for effective solutions in diabetic wound care.

Abstract Objective The effects of exercise on the health of people with Crohn’s disease (CD) remain unclear. This study aimed to explore the perspective of Chinese CD patients on exercise and the quantitative relationship between exercise and patient-reported outcomes. Methods This study used a mixed methods design consisting of three components. (1) Big data were mined from social media, and latent Dirichlet allocation (LDA) was used to perform cluster analysis on topics related to physical exercise. (2) A seven-step Colaizzi process was used to conduct semistructured interviews to obtain in-depth information about exercise. (3) A cross-sectional study was performed to examine this relationship using the Global Physical Activity Questionnaire (GPAQ) and Patient-reported Outcome Measurement Information System (PROMIS). Results LDA yielded a total of 1536 exercise-related posts; eight topics concerning CD patients were obtained through clustering (peer support, exercise therapy, diet, fatigue, exercise type, intestinal symptoms, body constitution and mental health), and 11 patients were interviewed to validate the results of LDA and explore the insight of Chinese CD. We identified two themes: the effects of exercise on people with CD and factors that promote and hinder exercise. A total of 119 patients with CD were surveyed. Considering confounding factors such as disease activity and medication, moderate-intensity recreational PA increased patients’ physical function and improved anxiety, depression, fatigue, pain intensity, and pain impact (all p

Abstract This study aims to quantify fundus tessellated (FT) density and optic disc (OD) morphology using deep learning (DL) techniques and to investigate the correlations between these fundus characteristics and refractive function in young patients with myopia. We constructed two DL-based segmentation models to delineate the FT, OD, peripapillary atrophy (PPA), and macula at a pixel-level resolution. The study sought to identify differences in fundus characteristics between eyes categorized as having high myopia versus mild or moderate myopia. Furthermore, the correlation between fundus measurements and various ocular parameters was statistically analyzed. Correlation analysis indicated that the spherical equivalent and axial length were significantly associated with all fundus measurements (p

Abstract BackgroundPostpartum depression (PPD) is a prevalent mental health issue with significant impacts on mothers and families. Exploring reliable predictors is crucial for the early and accurate prediction of PPD, which remains challenging. ObjectiveThis study aimed to comprehensively collect variables from multiple aspects, develop and validate machine learning models to achieve precise prediction of PPD, and interpret the model to reveal clinical implications. MethodsThis study recruited pregnant women who delivered at the West China Second University Hospital, Sichuan University. Various variables were collected from electronic medical record data and screened using least absolute shrinkage and selection operator penalty regression. Participants were divided into training (1358/2055, 66.1%) and validation (697/2055, 33.9%) sets by random sampling. Machine learning–based predictive models were developed in the training cohort. Models were validated in the validation cohort with receiver operating curve and decision curve analysis. Multiple model interpretation methods were implemented to explain the optimal model. ResultsWe recruited 2055 participants in this study. The extreme gradient boosting model was the optimal predictive model with the area under the receiver operating curve of 0.849. Shapley Additive Explanation indicated that the most influential predictors of PPD were antepartum depression, lower fetal weight, elevated thyroid-stimulating hormone, declined thyroid peroxidase antibodies, elevated serum ferritin, and older age. ConclusionsThis study developed and validated a machine learning–based predictive model for PPD. Several significant risk factors and how they impact the prediction of PPD were revealed. These findings provide new insights into the early screening of individuals with high risk for PPD, emphasizing the need for comprehensive screening approaches that include both physiological and psychological factors.

Purpose To develop an artificial intelligence algorithm to automatically identify the anterior segment structures and assess multiple parameters of primary angle closure disease (PACD) in ultrasound biomicroscopy (UBM) images.Design Development and validation of an artificial intelligence algorithm for UBM images.Methods:2339 UBM images from 592 subjects were collected for algorithm development. A multitissue segmentation model based on deep learning was developed for automatic identification of anterior segments and localisation of scleral spur. Then, measurement of the typical angle parameters was performed from the predicted results, including angle-opening distance at 500 µm (AOD 500), trabecular–ciliary angle (TCA) and iris area. We then collected 222 UBM images from 45 subjects in two centres for model validation.Results The multitissue identification model established in this study reached mean Intersection over Union (IoU) of 0.98, 0.98 and 0.98 on cornea segmentation, iris segmentation and ciliary body segmentation and a mean error distance of 1.07 pixels on scleral spur localisation. Our model got a mean IoU of 0.98, 0.98 and 0.99 on cornea segmentation, iris segmentation and ciliary body segmentation and a mean error distance of 0.49 pixels on scleral spur localisation in open-angle images and received 0.98, 0.98, 0.978 and 1.42 pixels respectively in angle-closure images. The mean differences between automatic and manual measurement of the angle parameters were 3.07 μm of AOD, 3.34 degrees of TCA and 0.05 mm2 of iris area.Conclusions The automatic method of multitissue identification for PACD eyes developed was feasible, and the automatic measurement of angle parameters was reliable.

Abstract Background Epigenetic modifications are crucial in tumourigenesis, yet the changes in novel epigenetic regulators like 5‐hydroxymethylcytosines (5hmC) during the evolution of gastric premalignant lesions remain poorly understood. This study aims to investigate the implications of 5hmC in the progression from gastric premalignant lesions to gastric adenocarcinoma (GAC). Methods To our knowledge, we conducted the largest and longest longitudinal study of a Chinese population with gastric precursor lesions, involving 29,176 patients with gastritis who underwent gastroscopy and biopsy between 2001 and 2015, with follow‐up until 1 August, 2022. The median follow‐up time was 12.2 years, and the overall GAC incidence rate was 0.82%. Genome‐wide mapping of 5hmC in gastric premalignant lesions from a subset of individuals was performed using the 5hmC‐Seal assay, including 21 samples that progressed to GAC during follow‐up and 48 non‐progressed age‐ and sex‐matched controls. Results We identified 213 differentially modified gene bodies, primarily concentrated in pathways related to cell division, cell cycle, energy metabolism, inflammation and tumourigenesis. An exploratory study was conducted to summarize a 5hmC‐based epigenetic model for predicting cancer progression using multivariable logistic regression and machine learning. The nine‐gene model showed an area under the curve of 87.5% (95% confidence interval: 72%–100%) in the validation samples (one of three), which were set aside before model training. Conclusions This study is the first to explore the 5hmC molecular landscape in gastric premalignant lesions, suggesting relevant pathways implicated in their evolution to GAC as well as the feasibility of exploiting genome‐wide 5hmC mapping in assessing the risk of future cancer progression. Key points A largest longitudinal follow‐up study of gastric precursor lesions in Chinese patients. Revealing novel 5hmC molecular landscape linked to gastric premalignant lesions. The feasibility of an innovative 5hmC‐based predictive model for assessing gastric cancer progression risk.

Abstract Objectives Parkinson disease (PD) is the third leading cause of mortality among middle‐aged and older individuals in China. This study aimed to explore the trends and distribution features of PD mortality in China from 2013 to 2021 and make predictions for the next few decades. Methods Relevant data were obtained from the Chinese Center for Disease Control and Prevention Disease Surveillance Point system. The joinpoint regression model was used to evaluate trends. The R software was used to predict future trends. Results Age‐standardized mortality rate (ASMR) of PD increased from 0.59 per 100,000 individuals to 1.22 per 100,000 individuals from 2013 to 2021, with an average annual percent change (AAPC) of 9.50 (95% CI: 8.24–10.78). The all‐age ASMR of PD were higher in male individuals than in female individuals, and ASMR increased with age. The number of deaths and ASMR increased gradually from west to east and from rural to urban areas. Furthermore, ASMR is expected to increase to 2.66 per 100,000 individuals by 2040. Conclusions The heightened focus on the ASMR of PD among male individuals, urban areas, eastern China, and individuals aged ≥85 years has become a key determinant in further decreasing mortality, thereby exhibiting novel challenges to effective strategies for disease prevention and control.

Abstract Background Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. Methods Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. Results In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 − 16.39/100,000) in 2021, with an EPAC for ASIR

Abstract Background The current study sought to investigate the correlation between vitamin D supplementation in pregnant women with vitamin D deficiency in early pregnancy and the incidence of prenatal depression prior to delivery. Methods This is a retrospective, single-center study that was conducted at a tertiary hospital in Chengdu, China. We conducted an analysis on pregnant women who were initially diagnosed with vitamin D deficiency at 12–14 weeks of gestation. After starting vitamin D supplementation at a dose of 800 IU daily from 14 weeks onwards, we measured both their vitamin D concentration and depression scores again during median gestational week 39 prior to delivery. Results The study cohort comprised 1365 women who had been diagnosed with vitamin D deficiency at 12–14 weeks of gestation between November 1st, 2021 to November 1st, 2022. 537 pairs were matched based on a propensity score to control for other confounding factors. After propensity score matching, the baseline vitamin D levels were made consistent between the groups (P = 0.512). The incidence of depression in patients in vitamin D deficiency group following vitamin D supplementation was significantly higher than insufficiency group and reached statistical significance (P

ObjectivesTo evaluate the diagnostic accuracy of the quantitative flow ratio (QFR) for hemodynamic exploration of intracranial atherosclerotic stenosis, using the invasive cerebrovascular pressure ratio (CVPR) and resting full-cycle ratio (RFR) as reference standards.Materials and methodsPatients with symptomatic unifocal intracranial atherosclerotic stenosis were included. The CVPR was defined as the ratio of the proximal and distal pressures. All patients underwent angioplasty under general anesthesia. The QFR was calculated based on digital subtraction angiography. Using the CVPR as a reference, we compared its correlation with the QFR across different degrees and locations of stenosis.ResultsThe CVPR and QFR were measured in 34 vessels of 32 patients. The QFR demonstrated a high correlation and excellent agreement(r = 0.8227, p 80%, the QFR showed a high correlation (r = 0.8812, p

Perinatal depression (PD), which affects about 10–20 percent of women, often goes unnoticed because related symptoms frequently overlap with those commonly experienced during pregnancy. Moreover, identifying PD currently depends heavily on the use of questionnaires, and objective biological indicators for diagnosis has yet to be identified. This research proposes a safe and non-invasive method for diagnosing PD and aims to delve deeper into its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram (EEG) for mothers-to-be and fetuses, we collected the resting-state scalp EEG of pregnant women (with PD/healthy) at the 38th week of gestation. To compensate for the low spatial resolution of scalp EEG, source analysis was first applied to project the scalp EEG to the cortical-space. Afterwards, cortical-space networks and large-scale networks were constructed to investigate the mechanism of PD from two different level. Herein, differences in the two distinct types of networks between PD patients and healthy mothers-to-be were explored, respectively. We found that the PD patients illustrated decreased network connectivity in the cortical-space, while the large-scale networks revealed weaker connections at cerebellar area. Further, related spatial topological features derived from the two different networks were combined to promote the recognition of pregnant women with PD from those healthy ones. Meanwhile, the depression severity at patient level was effectively predicted based on the combined spatial topological features as well. These findings consistently validated that the two kinds of networks indeed played off each other, which thus helped explore the underlying mechanism of PD; and further verified the superiority of the combination strategy, revealing its reliability and potential in diagnosis and depression severity evaluation.

Edge computing has attracted wide attention due to its ultra-low latency services, as well as the prevalence of smart devices and intelligent applications. Edge server placement (ESP) is one of the key issues needed to be addressed for effective and efficient request processing, by deciding which edge stations to equip with limited edge resources. Due to NP-hardness of ESP, some works have designed meta-heuristic algorithms for solving it. While these algorithms either exploited only one kind of meta-heuristic search strategies or separately perform two different meta-heuristic algorithms. This can result in limit performance of ESP solutions due to the “No Free Lunch” theorem. In addition, existing algorithms ignored the computing delay of edge servers (ESs) on request process, resulting in overestimation of the service quality. To address these issues, in this article, we first formulate ESP problem with the objective of minimizing the overall response time, considering heterogeneous edge servers with various service capacity. Then, to search effective or even the best ESP solutions, we propose a hybrid meta-heuristic algorithm (named GP4ESP) by taking advantage of both the powerful global search ability of genetic algorithm (GA) and the fast convergence of particle swarm optimization (PSO). GP4ESP effectively fuses the merits of GA and PS by integrating the swarm cognition of PSO into the evolutionary strategy of GA. At last, we conducted extensive simulation experiments to evaluate the performance of GP4ESP, and results show that GP4ESP achieves 18.2%–20.7% shorter overall response time, compared with eleven up-to-date ESP solving algorithms, and the performance improvement is stable as the scale of ESP is varied.

Oxidative stress, infection, and vasculopathy caused by hyperglycemia are the main barriers for the rapid repair of foot ulcers in patients with diabetes mellitus (DM). In recent times, the discovery of neddylation, a new type of post-translational modification, has been found to regulate various crucial biological processes including cell metabolism and the cell cycle. Nevertheless, its capacity to control the healing of wounds in diabetic patients remains unknown. This study shows that MLN49224, a compound that inhibits neddylation at low concentrations, enhances the healing of diabetic wounds by inhibiting the polarization of M1 macrophages and reducing the secretion of inflammatory factors. Moreover, it concurrently stimulates the growth, movement, and formation of blood vessel endothelial cells, leading to expedited healing of wounds in individuals with diabetes. The drug is loaded into biomimetic macrophage-membrane-coated PLGA nanoparticles (M-NPs/MLN4924). The membrane of macrophages shields nanoparticles from being eliminated in the reticuloendothelial system and counteracts the proinflammatory cytokines to alleviate inflammation in the surrounding area. The extended discharge of MLN4924 from M-NPs/MLN4924 stimulates the growth of endothelial cells and the formation of tubes, along with the polarization of macrophages towards the anti-inflammatory M2 phenotype. By loading M-NPs/MLN4924 into a hydrogel, the final formulation is able to meaningfully repair a diabetic wound, suggesting that M-NPs/MLN4924 is a promising engineered nanoplatform for tissue engineering.

Abstract Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.

Abstract. Background:. Cerebrovascular disease (CVD) ranks among the foremost factors responsible for mortality on a global scale. The mortality patterns of CVDs and temporal trends in China need to be well-illustrated and updated. Methods:. We collected mortality data on patients with CVD from Chinese Center for Disease Control and Prevention's Disease Surveillance Points (CDC-DSP) system. The mortality of CVD in 2020 was described by age, sex, residence, and region. The temporal trend from 2013 to 2019 was evaluated using joinpoint regression, and estimated rates of decline were extrapolated until 2030 using time series models. Results:. In 2019, the age-standardized mortality in China (ASMRC) per 100,000 individuals was 113.2. The ASMRC for males (137.7/105) and rural areas (123.0/105) were both higher when stratified by gender and urban/rural residence. The central region had the highest mortality (126.5/105), the western region had a slightly lower mortality (123.5/105), and the eastern region had the lowest mortality (97.3/105). The age-specific mortality showed an accelerated upward trend from aged 55–59 years, with maximum mortality observed in individuals over 85 years of age. The age-standardized mortality of CVD decreased by 2.43% (95% confidence interval, 1.02–3.81%) annually from 2013 to 2019. Notably, the age-specific mortality of CVD increased from 2013 to 2019 for the age group of over 85 years. In 2020, both the absolute number of CVD cases and the crude mortality of CVD have increased compared to their values in 2019. The estimated total deaths due to CVD were estimated to reach 2.3 million in 2025 and 2.4 million in 2030. Conclusion:. The heightened focus on the burden of CVD among males, rural areas, the central and western of China, and individuals aged 75 years and above has emerged as a pivotal determinant in further decreasing mortalities, consequently presenting novel challenges to strategies for disease prevention and control.

It is imperative to develop and implement newer, more effective strategies to address refractory diabetic wounds. As of now, there is currently no optimal solution for these wounds. Hypoxic human umbilical vein endothelial cells (HUVECs)-derived exosomes have been postulated to promote diabetic wound healing, however, its effect and molecular mechanism need further study. In this study, we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics. Based on our high-throughput sequencing, differentially expressed lncRNAs (including 64 upregulated lncRNAs and 94 downregulated lncRNAs) were found in hypoxic exosomes compared to normoxic exosomes. Interestingly, lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes, showing a notable correlation with diabetic wound healing. More specifically, hypoxic exosomes were transmitted to surrounding cells, which resulted in a significant increase in lncHAR1B level, thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions. Mechanistically, lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23 (BHLHE23), which subsequently led to its binding to the KLF transcription factor 4 (KLF4) and promoted KLF4 expression. In our in vivo experiments, the use of hypoxic exosomes-loaded HGM-QCS hydrogels (Gel-H-Exos) resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels (Gel-N-Exos) and diabetic groups. Consequently, our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.

Balancing detection performance and computational efficiency is critical for sustainable pavement disease detection in energy-constrained scenarios. However, existing visual methods often struggle to adapt to structural transformations and capture critical features of pavement diseases in complex environments, while their computational demands can be resource-intensive. To address these challenges, this paper proposes a structure perception and feature attention network (SPFAN). The network includes a structure perception module that employs the updated deformable convolution technique. This technique enables the model to dynamically adjust and focus on the actual pavement disease regions, improving the accuracy of feature extraction, especially for diseases with irregular shapes and sizes. Additionally, the convolutional block attention module (CBAM) is integrated to optimize feature map attention across channel and spatial dimensions, enhancing the model focus on critical disease features without significantly increasing complexity. To further improve robustness, the generalized intersection over union (GIoU) loss function is adopted, ensuring better stability across targets of varying shapes and sizes. Experimental results on real-world pavement disease images show that the mAP@0.5 of the proposed SPFAN increases from 66.2% to 71.2%, an improvement of 7.55%, while the F1-score also increases by 9.03%, compared to the baseline YOLOv8n model. Furthermore, while achieving significant accuracy improvements, the proposed method maintains a similar parameter count as the baseline, preserving its low computational demands and high efficiency, making it suitable for real-time pavement damage detection in energy-constrained environments.

Purpose: To develop and validate deep learning algorithms that can identify and classify angle-closure (AC) mechanisms using anterior segment optical coherence tomography (AS-OCT) images. Methods: This cross-sectional study included participants of the Handan Eye Study aged ≥35 years with AC detected via gonioscopy or on the AS-OCT images. These images were classified by human experts into the following to indicate the predominant AC mechanism (ground truth): pupillary block, plateau iris configuration, or thick peripheral iris roll. A deep learning architecture, known as comprehensive mechanism decision net (CMD-Net), was developed to simulate the identification of image-level AC mechanisms by human experts. Cross-validation was performed to optimize and evaluate the model. Human-machine comparisons were conducted using a held-out and separate test sets to establish generalizability. Results: In total, 11,035 AS-OCT images of 1455 participants (2833 eyes) were included. Among these, 8828 and 2.207 images were included in the cross-validation and held-out test sets, respectively. A separate test was formed comprising 228 images of 35 consecutive patients with AC detected via gonioscopy at our eye center. In the classification of AC mechanisms, CMD-Net achieved a mean area under the receiver operating characteristic curve (AUC) of 0.980, 0.977, and 0.988 in the cross-validation, held-out, and separate test sets, respectively. The best-performing ophthalmologist achieved an AUC of 0.903 and 0.891 in the held-out and separate test sets, respectively. And CMD-Net outperformed glaucoma specialists, achieving an accuracy of 89.9 % and 93.0 % compared to 87.0 % and 86.8 % for the best-performing ophthalmologist in the held-out and separate test sets, respectively. Conclusions: Our study suggests that CMD-Net has the potential to classify AC mechanisms using AS-OCT images, though further validation is needed.

Polygonatum odoratum is widely recognized to conribute to various health benefits, primarily attributed to its polysaccharide (POP). Polysaccharides are not directly and readily absorbed by the gastrointestinal system, but can interact with the gut microbes. This study aims to clarify the mechanism of POP in mitigating and preventing OVA-induced allergic airway inflammation via the gut-lung axis. The results showed that POP improved the symptoms associated with allergic respiratory responses, and the efficacy of POP was impeded due to the disruption of gut microbiota caused by antibiotics. The POP altered gut microbiota effectively alleviated the type 2 inflammation, reduced the number of ILC2s in the lung and gut, and inhibited the movement of intestinal ILC2s towards the lung. Clostridia UCG-014 and Rikenellaceae RC9 were figured out as pathogenic bacteria inhibited by POP. This study provides a reference for therapeutic application of POP in managing allergic airway inflammation via the gut-lung axis.

Background: Retinal health indices were suggested to be related to psychopathological symptoms, such as depressive symptoms. However, large-scale studies using optical coherence tomography (OCT) are missing to investigate the associations among them. Methods: In the META-KLS cohort study, 1456 participants (mean age [standard deviation]= 54.6 [11.91] years; n= 680 [47.8%] women) completed the Patient Health Questionnaire (PHQ-9) to measure depressive symptoms and underwent OCT. Poor-quality OCTs and multivariate outliers were excluded, and principal component analysis was performed to obtain retinal health indices separately for macular (n= 930) and optic nerve head (ONH) thicknesses (n= 800). Linear regressions were run controlling for covariates. Exploratory interaction models were run with demographic, lifestyle and health markers. Results: Although there were no direct significant associations between the retinal indices and depressive symptoms (macular: B= −0.05, 95% CI= [-0.15, 0.05], p= 0.32; ONH index: B= -0.02, 95% CI= [-0.11, 0.08], p= 0.71), their associations were moderated by demographic and health factors, e.g., C-reactive protein (CRP) (macular index: B= −0.03, 95% CI= [-0.05, −0.01], p= 0.002; ONH index: B= 0.05, 95% CI= [0.02, 0.08], p= 0.002). Limitations: Study was cross-sectional and there were no functional assessments of vision. Conclusions: In a large cohort, we observed associations between retinal indices and self-reported depressive symptoms depending on demographic and health factors, notably CRP. Following up, the study will investigate the prospective prediction of retinal health on depressive symptoms, especially in persons who may have chronic inflammation.

Abstract Background Identifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients. Methods A total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors. Results Most PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAF V600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580–0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit. Conclusion Tumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

Abstract Background The current literature shows a strong relationship between retinal neuronal and vascular alterations in dementia. The purpose of the study was to use NFN+ deep learning models to analyze retinal vessel characteristics for cognitive impairment (CI) recognition. Methods We included 908 participants from a community-based cohort followed for over 15 years (the prospective KaiLuan Study) who underwent brain magnetic resonance imaging (MRI) and fundus photography between 2021 and 2022. The cohort consisted of both cognitively healthy individuals (N = 417) and those with cognitive impairment (N = 491). We employed the NFN+ deep learning framework for retinal vessel segmentation and measurement. Associations between Retinal microvascular parameters (RMPs: central retinal arteriolar / venular equivalents, arteriole to venular ratio, fractal dimension) and CI were assessed by Pearson correlation. P

Abstract Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content f c ranging from 0 to 20% at an initial mean effective stress of p 0′ = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= − 0.03) confirms that the sample with 10% f c exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio η s typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative η s is stiffer than that under isotropic consolidation, while the presence of a positive η s leads to a decrease in the secant Young's modulus.

Inflammatory bowel disease (IBD) comprises a collection of chronic, non-specific inflammatory disorders affecting the gastrointestinal tract, the exact causes of which remain undefined. Research has indicates that the elderly population accounts for 10%-20% of IBD cases, and the prevalence of IBD among the elderly is steadily increasing alongside the patient base. In comparison to their younger counterparts with IBD, genetic factors play a diminished role in the development of elderly IBD, whereas immune system dysregulation and disruptions in gut microbiota assume greater significance. Among the elderly, various other prevalent conditions frequently exhibit symptoms akin to IBD, thereby rendering diagnosis notably challenging. Given that both IBD and aging process independently constitute risk factors for malnutrition, the probability of concurrent malnutrition substantially escalates within this subgroup. However, the realm of research regarding malnutrition in elderly IBD patients remains constrained. This review delves comprehensively into the status of malnutrition among elderly IBD patients, encompassing aspects of screening, assessment, and dietary management.

BackgroundPostpartum depression (PPD) is one of the most common complications of delivery and is usually disregarded. Several risk factors of PPD have been identified, but its pathogenesis has not been completely understood. Serum bilirubin has been found to be a predictor of depression, whose relationship with PPD has not been investigated.MethodsObservational research was performed followed by a two-sample Mendelian randomization (MR) analysis. From 2017 to 2020, the clinical data of pregnant women were retrospectively extracted. Logistic regression and random forest algorithm were employed to assess the risk factors of PPD, including the serum levels of total bilirubin and direct bilirubin. To further explore their potential causality, univariable and multivariable Mendelian randomization (MVMR) were conducted. Sensitivity analyses for MR were performed to test the robustness of causal inference.ResultsA total of 1,810 patients were included in the PPD cohort, of which 631 (34.87%) were diagnosed with PPD. Compared with the control group, PPD patients had a significantly lower level of total bilirubin (9.2 μmol/L, IQR 7.7, 11.0 in PPD; 9.7 μmol/L, IQR 8.0, 12.0 in control, P < 0.001) and direct bilirubin (2.0 μmol/L, IQR 1.6, 2.6 in PPD; 2.2 μmol/L, IQR 1.7, 2.9 in control, P < 0.003). The prediction model identified eight independent predictive factors of PPD, in which elevated total bilirubin served as a protective factor (OR = 0.94, 95% CI 0.90–0.99, P = 0.024). In the MR analyses, genetically predicted total bilirubin was associated with decreased risk of PPD (IVW: OR = 0.86, 95% CI 0.76–0.97, P = 0.006), which remained consistent after adjusting educational attainment, income, and gestational diabetes mellitus. Conversely, there is a lack of solid evidence to support the causal relationship between PPD and bilirubin.ConclusionOur results suggested that decreased total bilirubin was associated with the incidence of PPD. Future studies are warranted to investigate its potential mechanisms and illuminate the pathogenesis of PPD.

Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.

AbstractAim High-intensity focused ultrasound (HIFU) is a non-invasive treatment of adenomyosis. Uterine rupture during pregnancy is a rare adverse event after HIFU treatment, because HIFU treatment results in tissue coagulative necrosis.Methods We reported a case of uterine rupture in a 34-year-old woman. The woman had HIFU treatment for adenomyosis eight months before unplanned pregnancy. She was closely monitored during the pregnancy and the antenatal course was uneventful. At the gestational age of 38 weeks and 2 days, an emergency lower segment cesarean section was performed because of inexplainable abdominal pain. After delivery of the fetus, a 2 × 2 cm serous membrane rupture was observed in the HIFU treatment area.Conclusion Uterine rupture during pregnancy after HIFU is a rare adverse event, however, attention is required during the whole pregnancy in case of unexpected uterine rupture.

Abstract Background Colorectal cancer (CRC) is a fatal malignant tumor with poor prognosis. Cancer stem cells (CSCs) can cause metastasis, recurrence and drug resistance in CRC. This research aimed to analyze stemness‐related prognostic genes of CRC based on single‐cell RNA‐sequencing (scRNA‐seq) data. Methods DESeq2 was applied to analyze the differentially expressed genes (DEGs). The mRNA stemness index (mRNAsi) was calculated by one‐class logistic regression (OCLR). The stemness‐related cells were analyzed based on scRNA‐seq dataset GSE166555. Monocle 2 algorithm was used for stemness‐related cells pseudotime trajectory analysis. The stemness‐related prognostic genes were analyzed by clusterProfiler and survival package. The stemness of CRC cells was detected by spheroid formation assay, and the expression of stemness‐related prognostic genes was verified by qRT‐PCR and Western blot. Results 7916 DEGs between the CRC and normal tissues were obtained. The mRNAsi of the CRC tissues was shown to be significantly higher than that of the normal tissues. 7 and 8 cell types were annotated respectively in the normal and CRC tissues through analysis of the scRNA‐seq data. Cell–cell interactions (CCIs) in the tumor tissues were revealed to be significantly enhanced than that in the normal tissues. By calculating the ‘stemness score’, CSCs, epithelial cells (EPCs) and cancer‐associated fibroblasts (CAFs) were defined as stemness‐related cells. Through pseudotime trajectory analysis, 2111 genes were identified as state 2‐specific genes. Then, 41 genes were obtained by taking intersection of the up‐regulated genes with state 2‐specific genes and marker genes of CSCs, EPCs and CAFs. The univariate COX regression analysis revealed 5 stemness‐related prognostic genes (TIMP1, PGF, FSTL3, SNAI1 and FOXC1). Kaplan–Meier curve analysis indicated that the higher the expression of 5 genes, the lower the survival rate. In vitro cell experiment confirmed that the expression of TIMP1, PGF and SNAI1 was consistent with that revealed by bioinformatics analysis. Conclusions TIMP1, PGF and SNAI1 were identified as stemness‐related prognostic genes of CRC, and possibly potential therapeutic targets for CRC.

Abstract Aim The aim of this study was to explore the experience and perceptions of patients with Crohn’s disease in China. Methods Data mining was used to investigate posts in Crohn’s disease online medical communities. The data were collected through the crawler code, and latent Dirichlet allocation (LDA) and grounded theory were used to mine the theme features after data cleaning. Results In analyzing the topic characteristics of online posts, LDA divided 6757 posts into 15 topics on four aspects: seeking disease information, making decisions on medication use, psychological burden, and communicating about diet and nutrition. Conclusion Overall, social media is patient-centric and helps us better understand the experiences and perceptions of patients. This study can help medical staff predict the thoughts and concerns of Crohn's disease patients during the treatment process, facilitate doctor-patient communication, and assist in the formulation of medical policies.

Abstract There are significant risks of adverse events following oesophageal endoscopic submucosal dissection (ESD), such as stricture, delayed bleeding and perforation. Therefore, it is necessary to protect artificial ulcers and promote the healing process. The current study was performed to investigate the protective role of a novel gel against oesophageal ESD-associated wounds. This was a multicentre, randomized, single-blind, controlled trial that recruited participants who underwent oesophageal ESD in four hospitals in China. Participants were randomly assigned to the control or experimental group in a 1:1 ratio and the gel was used after ESD in the latter. Masking of the study group allocations was only attempted for participants. The participants were instructed to report any adverse events on post-ESD days 1, 14, and 30. Moreover, repeat endoscopy was performed at the 2-week follow-up to confirm wound healing. Among the 92 recruited patients, 81 completed the study. In the experimental group, the healing rates were significantly higher than those in the control group (83.89 ± 9.51% vs. 73.28 ± 17.81%, P = 0.0013). Participants reported no severe adverse events during the follow-up period. In conclusion, this novel gel could safely, effectively, and conveniently accelerate wound healing following oesophageal ESD. Therefore, we recommend applying this gel in daily clinical practice.

Abstract Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at −20 °C or −70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.

BackgroundEndoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the “eCura system” is reliable for the risk stratification of LNM after non-curative ESD.MethodsWe conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the “eCura system”.ResultsAmong 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively).ConclusionClinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the “eCura system”, additional surgery should be performed in patients with intermediate/high risk of LNM.

Summary: Background: The disease burden of gastrointestinal disease (GD) in China is high, with significant variation across provinces. A comprehensive agreed set of indicators could guide rational resource allocation to support better GD outcomes. Methods: This study collected data from multiple sources, including national surveillance, surveys, registration systems, and scientific research. Literature reviews and Delphi methods were used to obtain monitoring indicators; the analytic hierarchy process was used to determine indicator weights. Findings: The China Gastrointestinal Health Index (GHI) system consisted of four dimensions and 46 indicators. The weight of the four dimensions from high to low included the prevalence of gastrointestinal non-neoplastic diseases and gastrointestinal neoplasms (GN) (0.3246), clinical treatment of GD (0.2884), prevention and control of risk factors (0.2606), and exposure to risk factors (0.1264). The highest indicator weight of GHI rank was the successful smoking cessation rate (0.1253), followed by the 5-year survival rate of GN (0.0905), and the examination rate of diagnostic oesophagogastroduodenoscopy (0.0661). The overall GHI for China in 2019 was 49.89, varying from 39.19 to 76.13 across all sub-regions. The top five sub-regions in the total GHI score were in the eastern region. Interpretation: GHI is the first system designed to monitor gastrointestinal health systematically. In the future, data from sub-regions of China should be used to test and improve the GHI system for its impact. Funding: This research was supported by the National Health Commission of China, the First Affiliated Hospital of Naval Medical University (2019YXK006), and the Science and Technology Commission of Shanghai Municipality (21Y31900100).

Abstract A more complete taxi pick‐ups prediction going beyond the conditional expectation would be more beneficial to allocate taxis effectively. Prior works have predicted the conditional expectation of taxi demand and improved the prediction accuracy. But the ability to convey calibrated uncertainty estimates in prediction was less studied. Here, a multi‐output multi‐quantile deep neural network architecture is presented for predicting the mean and the multiple quantiles simultaneously, which jointly models multiple quantiles together with the conditional expectation based on self‐attention ConvLSTM. Using the NYC taxi dataset, we have analyzed the performance of the developed architecture. For the mean prediction, the proposed method has an error of 8.584 in terms of RMSE criteria and Linear QR, Mcdropout‐Gal, ConvLSTM and SA‐ConvLSTM methods, which have error values of 8.800, 8.671, 8.599, and 8.597, respectively. According to the MAE criterion, this method has a value of 5.934. The other methods have obtained values of 6.614, 5.990, 5.986, and 5.959, respectively. For multiple quantiles prediction, the proposed method produces narrower intervals while obtaining the target coverage percentage. Overall, the proposed model not only outperforms the other models, but also provides a rich description about the predictive density.

An efficient Cu-catalyzed strategy for the direct C–H amination of arenes in high yields using N-hydroxyphthalimide as the amidyl radical precursor under air is reported. A possible mechanism is proposed that proceeds via a radical reaction in the presence of CuBr and triethyl phosphite.

The aquaculture of marine ranching is of great significance for scientific aquaculture and the practice of statistically grasping existing information on the types of living marine resources and their density. However, underwater environments are complex, and there are many small and overlapping targets for marine organisms, which seriously affects the performance of detectors. To overcome these issues, we attempted to improve the YOLOv8 detector. The InceptionNeXt block was used in the backbone to enhance the feature extraction capabilities of the network. Subsequently, a separate and enhanced attention module (SEAM) was added to the neck to enhance the detection of overlapping targets. Moreover, the normalized Wasserstein distance (NWD) loss was proportionally added to the original CIoU loss to improve the detection of small targets. Data augmentation methods were used to improve the dataset during training to enhance the robustness of the network. The experimental results showed that the improved YOLOv8 achieved the mAP of 84.5%, which was an improvement over the original YOLOv8 of approximately 6.2%. Meanwhile, there were no significant increases in the numbers of parameters and computations. This detector can be applied on platforms for seafloor observation experiments in the field of marine ranching to complete the task of real-time detection of marine organisms.

Abstract Gastric adenocarcinoma is major type of gastric cancer that endangers human health. AKIRIN2 has been shown to be associated with cholangiocarcinoma promoting invasion and angiogenesis. In this study, AKIRIN2 is highly expressed in Gastric adenocarcinoma through bioinformatics analysis based on Stomach adenocarcinoma samples data from The Cancer Genome Atlas. Correlation analysis showed that the high-expression of AKIRIN2 was associated with poor survival rate compared to the low-expression group. Univariate and multivariate Cox regression analyses determined the correlation between clinical characteristics and overall survival. Next, the correlation between AKIRIN2 and immune infiltration was evaluated. The distribution of 24 immune cells and their correlation with the expression of AKIRIN2 were explored using the immune cell database. In addition, three Immune cell methods were used to verify the positive correlation between immune cells and AKIRIN2. Also, Genomics of Drug Sensitivity in Cancer database was utilized to verify the correlation between AKIRIN2 expression level and the efficacy of chemotherapy and immunotherapy. The results showed that AKIRIN2 is an effective biomarker of Gastric adenocarcinoma prognosis, which can guide chemotherapy and immunotherapy and clarify the progress of Gastric adenocarcinoma promoted by immune microenvironment.

Abstract Purpose To develop a deep learning-based framework to improve the image quality of optical coherence tomography (OCT) and evaluate its image enhancement effect with the traditional image averaging method from a clinical perspective. Methods 359 normal eyes and 456 eyes with various retinal conditions were included. A deep learning framework with high-resolution representation was developed to achieve image quality enhancement for OCT images. The quantitative comparisons, including expert subjective scores from ophthalmologists and three objective metrics of image quality (structural similarity index measure (SSIM), peak signal-to-noise ratio (PSNR) and contrast-to-noise ratio (CNR)), were performed between deep learning method and traditional image averaging. Results With the increase of frame count from 1 to 20, our deep learning method always obtained higher SSIM and PSNR values than the image averaging method while importing the same number of frames. When we selected 5 frames as inputs, the local objective assessment with CNR illustrated that the deep learning method had more obvious tissue contrast enhancement than averaging method. The subjective scores of image quality were all highest in our deep learning method, both for normal retinal structure and various retinal lesions. All the objective and subjective indicators had significant statistical differences (P

Purpose: Voriconazole (VOR) is combined with atorvastatin (ATO) to treat fungal infections in patients with dyslipidemia in clinical practice. However, the pharmacokinetic interactions and potential mechanisms between them are unknown. Therefore, this study aimed to investigate the pharmacokinetic interactions and potential mechanisms between ATO and VOR.Patients and methods: We collected plasma samples from three patients using ATO and VOR. Rats were administered either VOR or normal saline for 6 days, followed by a single dose of 2 mg/kg ATO, and then plasma samples were collected at different time points. The incubation models of human liver microsomes or HepG2 cells were constructed in vitro. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system was developed to determine the concentration of ATO, 2-hydroxy-ATO, 4-hydroxy-ATO, and VOR.Results: In patients, VOR significantly reduced the metabolism of ATO and slowed the formation of 2-hydroxy- and 4-hydroxy-ATO. In rats pretreated with orally administered VOR for 6 days or normal saline given a single dose of 2 mg/kg ATO administered orally on Day 6, the t1/2 of ATO was significantly prolonged from 3.61 to 6.43 h, and the area under the concentration-time curve (AUC0–24h) values of ATO increased from 53.86 to 176.84 h μg.L−1. However, the pharmacokinetic parameters of VOR (20 mg/kg) with or without pretreatment with ATO (2 mg/kg) only slightly changed. In vitro studies indicated that VOR inhibited the metabolism of ATO and testosterone, and the IC50 values were 45.94 and 49.81 μM. However, no significant change in transporter behaviors of ATO was observed when VOR or transporter inhibitors were co-administered.Conclusion: Our study demonstrated that VOR has significant interactions with ATO, probably due to VOR’s inhibition of the CYP3A4-mediated metabolism of ATO. Based on the clinical cases and potential interactions, the basic data obtained in our study are expected to help adjust the dose of ATO and promote the design of rational dosage regimens for pharmacotherapy for fungal infections in patients with dyslipidemia.

Abstract Cervical adenocarcinomas (ADCs), including human papillomavirus (HPV)‐associated (HPVA) and non‐HPVA (NHPVA), though exhibiting a more malignant phenotype and poorer prognosis, are treated identically to squamous cell carcinoma (SCC). This clinical dilemma requires a deeper investigation into their differences. Herein a transcriptomic atlas of SCC, HPVA, and NHPVA‐ADC using single‐cell RNA (scRNA) and T‐cell receptor sequencing (TCR‐seq) is presented. Regarding structural cells, the malignancy origin of epithelial cells, angiogenic tip cells and two subtypes of fibroblasts is revealed. The promalignant properties of the structural cells using organoids are further confirmed. Regarding immune cells, myeloid cells with multiple functions other than antigen presentation and exhausted T lymphocytes contribute to immunosuppression. From the perspective of HPV infection, not only is HPV‐dependent and independent cervical cancer oncogenesis proposed but also three immune reaction patterns mediated by T cells (coordinated/inactive/imbalanced) are identified. Strikingly, diagnostic biomarkers to distinguish ADC from SCC are discovered and prognostic biomarkers with marker genes for malignant epithelial cells, tip cells, and SPP1/C1QC macrophages are generated. Importantly, the efficacy of anti‐CD96 and anti‐TIGIT, not inferior to anti‐PD1, in animal experiments is confirmed and targeted therapies specifically for HPV‐positive SCC, HPVA and NHPVA‐ADC, providing essential clues for further clinical trials, are proposed.

Background and objectivesThe routine application of lymphadenectomy remains a controversial part of surgical staging in malignant ovarian germ-cell tumor (MOGCT). Thus, studies are needed to explore the prognostic significance of lymphadenectomy in MOGCT. The goal of this retrospective study was to report the clinical outcomes of lymph node dissection (LND) and non-LND in MOGCT surgeries.Measurements and main resultsA total of 340 cases of MOGCTs were included: 143 patients (42.1%) had LND and 197 (57.9%) had no LND. The OS rates at 5 years in the LND and non-LND group were 99.3% vs. 100%, respectively. The DFS rates at 5 years in the LND and non-LND group were 88.8% vs. 88.3%. Forty-three patients (12.6%) were successfully pregnant during the postoperative follow-up. There were 44 recurrences (12.9%) and six deaths (1.8%). Stage was an independent prognostic factor for DFS in the multivariate analysis. Pathology was reported as an independent prognostic factor associated with OS in the multivariate analysis.ConclusionLymphadenectomy had no significant influence on the OS (P=0.621) or disease-free survival rate (P=0.332) of patients with MOGCT.

Summary: Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88–0.92 in the internal verification and 0.83–0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

Objectives: This study aimed to explore the distribution features and trends of dementia mortality in China from 2011 to 2020 and make a prediction for the next decade.Methods: Mortality-relevant data were gathered from the Chinese Center for Disease Control and Prevention’s Disease Surveillance Points system. Joinpoint regression was applied to evaluate the trends.Results: Crude Mortality Rate (CMR) of AD and other dementias increased from 3.7 per 100,000 to 6.2 per 100,000 in 2011–2020, with an Average Annual Percent Change (AAPC) of 5.3% (95% CI 4.4%–6.3%). Age-Standardized Mortality Rate (ASMR) slightly decreased from 5.0 per 100,000 to 4.1 per 100,000 in 2011–2020, with AAPC of −0.4% (95% CI −2.5%–1.8%). CMR will increase to 9.66 per 100,000 while ASMR will decline to 3.42 per 100,000 in the following decade.Conclusion: The upward trend in CMR and downward trend in ASMR suggested the further development of population aging and dementia mortality in the past and future decades. In China, there were gender, urban-rural, regional and age differences.

To solve the ghosting artifacts problem in dynamic scene multi-scale exposure fusion, an improved multi-exposure fusion method has been proposed without ghosting based on the exposure fusion framework and the color dissimilarity feature of this study. This fusion method can be further applied to power system monitoring and unmanned aerial vehicle monitoring. In this study, first, an improved exposure fusion framework based on the camera response model was applied to preprocess the input image sequence. Second, the initial weight map was estimated by multiplying four weight items. In removing the ghosting weight term, an improved color dissimilarity feature was used to detect the object motion features in dynamic scenes. Finally, the improved pyramid model as adopted to retain detailed information about the poor exposure areas. Experimental results indicated that the proposed method improves the performance of images in terms of sharpness, detail processing, and ghosting artifacts removal and is superior to the five existing multi-exposure image fusion (MEF) methods in quality evaluation.

It is very common that taxi is used as a feeder mode to/from a metro station especially in third-tier cities of China. But research on taxi-metro integrated use is rather limited. This paper investigates the relationship between feeder-related built environment and taxi-metro integrated use by using taxi trajectory data in Lanzhou, China. Firstly, regression models are developed to explore the transfer distance of access/egress trips during peak hours. Then, the catchment area is delineated for collecting feeder-related environment variables. Finally, several negative binomial regressions are employed to examine the relationships between feeder-related built environment and taxi-metro integrated use during peak hours on weekdays. The results reveal that (a) people prefer to use taxi as feeder mode for metro access during morning peak hours and for metro egress during evening peak hours; (b) the transfer distance of taxi-metro integrated use is about 3.8 km; (c) higher mixed land use generates more taxi-metro integrated use during evening peak hours. Higher proportion of residential land use attracts more taxi-metro integrated use for metro access during morning peak hours. Those findings will help transport planners to develop tailored land-use interventions to improve transit accessibility and promote the sustainable multimodal travel.