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Abstract Background New graduate nurses often have certain potential safety hazards for patients due to insufficient knowledge and lack of clinical practice ability. To address these challenges, China has implemented a standardized training strategy. The improvements in the quality of this training involve not only the intervention of teaching methods but also the consideration of personality traits. Methods The application software based on the BFI-2 Chinese scale was utilized to administer personality tests to nursing students; nursing students were invited to scan the QR code and voluntarily fill in a questionnaire, including basic information, personality test results, and a professional self-efficacy test scale; offline paper-based theoretical examination results of nursing students were collected before and after training. The data was then analyzed using SPSS software version 26.0, which involved descriptive analysis, one-way between-groups analysis of variance (ANOVA) and Spearman correlation analysis. Results Based on the data, there were no observable differences in the theoretical results before and after training across different personality traits. In terms of skill assessment, conscientiousness exhibited the highest score at 78.91 ± 2.98 points, while negative emotionality showed the lowest score at 74.59 ± 2.12 points. These differences between different personality traits are statistically significant (P

Objectives To investigate the clinical epidemiological characteristics and occurrence of post-traumatic stress symptoms (PTSS) in patients with traumatic fractures, we sought to analyze the factors that influence the prognosis of a length of hospital stay (LOS) and provide valuable insights to prevent PTSS in fracture patients and improve their prognosis. Methods Inpatients with traumatic fractures were recruited from a third-class comprehensive general hospital in southwest China between November 2019 and October 2020. Case data of traumatic fracture patients were collected, and a questionnaire that included general information and basic fracture details was completed. The post-traumatic stress disorder Self-rating Scale was used to assess PTSS among the fracture inpatients. Results A total of 204 inpatients who experienced traumatic fractures were included in this study. Falls accounted for the largest proportion of traumatic fractures. A Cox's regression analysis revealed that serious injury [Hazard Ratio (HR) = 2.44, 95% Confidence Interval (CI): 1.33–4.46], critical illness during hospitalization (HR = 1.70, 95% CI: 1.13–2.54), and undergoing two surgeries (HR = 1.87, 95% CI: 1.20–2.93) were risk factors for longer LOS. Among the fracture patients, 30.39% exhibited positive PTSD symptoms, and physical activity during the fracture [Odds Ratio (OR) = 0.63, 95% CI: 0.45–0.88] and increased pain (OR = 3.34, 95% CI: 1.82–6.11) were identified as influencing factors. Conclusions Given the high detection rate of PTSS following traumatic fractures, it is crucial for relevant departments to implement targeted measures to protect high risk individuals. Furthermore, strengthening the care provided to the patients' physical and mental health is urgently needed to reduce the incidence of PTSS.

Abstract Background Circular RNAs (circRNAs) have been recognized as significant regulators of pulmonary hypertension (PH); however, the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown. Here, we identified co‐differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) under hypoxia. Methods Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types. Bioinformatic analysis was used to predict their putative biological function. Quantitative real‐time polymerase chain reaction, Cell Counting Kit‐8, and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1 (circPMS1) as well as its potential sponge mechanism in PASMCs, PMECs, and PCs. Results PASMCs, PMECs, and PCs exhibited 16, 99, and 31 differentially expressed circRNAs under hypoxia, respectively. CircPMS1 was upregulated in PASMCs, PMECs, and PCs under hypoxia and enhanced the proliferation of vascular cells. CircPMS1 may upregulate DEP domain containing 1 (DEPDC1) and RNA polymerase II subunit D expression by targeting microRNA‐432‐5p (miR‐432‐5p) in PASMCs, upregulate MAX interactor 1 (MXI1) expression by targeting miR‐433‐3p in PMECs, and upregulate zinc finger AN1‐type containing 5 (ZFAND5) expression by targeting miR‐3613‐5p in PCs. Conclusions Our results suggest that circPMS1 promotes cell proliferation through the miR‐432‐5p/DEPDC1 or miR‐432‐5p/POL2D axis in PASMCs, through the miR‐433‐3p/MXI1 axis in PMECs, and through the miR‐3613‐5p/ZFAND5 axis in PCs, which provides putative targets for the early diagnosis and treatment of PH.

Abstract Background The aim of the present study was to evaluate the impact of intratumoral metabolic heterogeneity and quantitative 18F‐FDG PET/CT imaging parameters in predicting patient outcomes in thymic epithelial tumors (TETs). Methods This retrospective study included 100 patients diagnosed with TETs who underwent pretreatment 18F‐FDG PET/CT. The maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were measured. Heterogeneity index‐1 (HI‐1; standard deviation [SD] divided by SUVmean) and heterogeneity index‐2 (HI‐2; linear regression slopes of the MTV according with different SUV thresholds), were evaluated as heterogeneity indices. Associations between these parameters and patient survival outcomes were analyzed. Results The univariate analysis showed that Masaoka stage, TNM stage, WHO classification, SUVmax, SUVmean, TLG, and HI‐1 were significant prognostic factors for progression‐free survival (PFS), while MTV, HI‐2, age, gender, presence of myasthenia gravis, and maximum tumor diameter were not. Subsequently, multivariate analyses showed that HI‐1 (p

WDR68, a conserved WD40 repeat-containing protein, interacts with E1A and is involved in the E1A-induced cell proliferation and oncogenic transformation, but the intrinsic molecular mechanisms of this process remain to be elucidated. Here, we demonstrate that WDR68 promotes the proliferation of 293T cells by interacting with a series of ribosome biogenesis-regulating proteins. Gene Set Enrichment Analysis (GSEA) of RNA-seq data also revealed that the ribosome biogenesis-associated gene signatures could be the most significantly enriched in the WDR68 expression groups. In accordance, 293T cells are more sensitive to the ribosome biogenesis inhibitors than 293 cells. Taken together, our results indicated that WDR68 could promote cell proliferation through the activation of ribosome biogenesis in the 293T cell context. This provides new insights into the understanding of the function of WDR68 and the molecular characterisation of 293T tool cells.

Purpose: Polypharmacy presents many challenges to patient medication self-management. This study aims to explore the self-management processes of medication in polypharmacy from the perspectives of both patients and healthcare providers, which can help identify barriers and facilitators to effective management.Methods: A systematic review of qualitative studies was performed by searching seven databases: PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, and MEDLINE, from their establishment until August 2024. The Critical Appraisal Skills Programme (CASP) tool was employed to evaluate the quality of the studies included. The extracted data were then analysed thematically and integrated into The Taxonomy of Everyday Self-management Strategies (TEDSS) framework.Results: A total of 16 studies were included, involving 403 patients and 119 healthcare providers. Patient management measures were mapped into TEDSS framework, including categories such as medical management, support-oriented domains, and emotional and role management.Conclusion: Enhancing patients’ proactive health awareness, improving medication literacy, balancing lifestyle adjustments with medication therapy, dynamically reviewing and optimizing medications, strengthening patients’ social support networks, and helping patients integrate medication management into their daily life are the key elements that can effectively assist patients in self-managing their medications. Future interventions to improve patient medication self-management ability should be designed for these issues.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024524742.

Trucks consume a lot of energy. Hybrid technology maintains a long range while realizing energy savings. Hybrid is therefore an effective energy-saving technology for trucks. Recovery of engine waste heat through the organic Rankine cycle further enhances engine efficiency and provides effective thermal management. However, the powertrain greatly increases the complexity of energy management system. In order to design an energy management system with high efficiency and robustness, this study proposes a deep reinforcement learning embedded rule-based energy management system. This method optimises the key parameters of the rule-based energy management system by inserting deep reinforcement learning into it. Therefore, this scheme combines the good optimization effect of deep reinforcement learning and the excellent robustness of rule. In order to verify the feasibility of this scheme, this study builds the system dynamic model and carries out a simulation study. Subsequently, a hybrid powertrain semi physical experimental bench was constructed and a rapid control prototype experimental study was carried out. The simulation results show that the deep reinforcement learning embedded rule-based energy management system can reduce the energy consumption by 4.31 % compared with the rule-based energy management system under the C-WTVC driving cycle. In addition, energy saving and safe operation can also be achieved under other unfamiliar untrained driving cycles. The rapid control prototype experimental study shows that the deep reinforcement learning embedded rule-based energy management system has good agreement in experiment and simulation, which demonstrates the potential for real vehicle engineering applications and promotes the engineering application of deep reinforcement learning.

Abstract Acute myocardial infarction (AMI), a critical manifestation of coronary heart disease, presents a complex and not entirely understood etiology. This study investigates the potential role of immune infiltration and endothelial-mesenchymal transition (EndoMT) in AMI pathogenesis. We conducted an analysis of the GSE24519 and MSigDB datasets to identify differentially expressed genes associated with the TGF-β signaling pathway (DE-TSRGs) and carried out a functional enrichment analysis. Additionally, we evaluated immune infiltration in AMI and its possible link to myocardial fibrosis. Key genes were identified using machine learning and LASSO logistic regression. The expression of MEOX1 in the ventricular muscles and endothelial cells of Sprague–Dawley rats was assessed through RT-qPCR, immunohistochemical and immunofluorescence assays, and the effect of MEOX1 overexpression on EndoMT was investigated. Our study identified five DE-TSRGs, among which MEOX1, SMURF1, and SPTBN1 exhibited the most significant associations with AMI. Notably, we detected substantial immune infiltration in AMI specimens, with a marked increase in neutrophils and macrophages. MEOX1 demonstrated consistent expression patterns in rat ventricular muscle tissue and endothelial cells, and its overexpression induced EndoMT. Our findings suggest that the TGF-β signaling pathway may contribute to AMI progression by activating the immune response. MEOX1, linked to the TGF-β signaling pathway, appears to facilitate myocardial fibrosis via EndoMT following AMI. These novel insights into the mechanisms of AMI pathogenesis could offer promising therapeutic targets for intervention.

Thiram (THI) and asomate (ASO) are frequently detected agrochemicals in food samples due to widespread use as fungicides. However, their detection suffers from matrix interference, or the necessity of derivatization before measurement. Integrating HPLC with a post-column carbon dots (CDs)–enhanced chemiluminescence (CL) system makes it possible to simultaneously separate and selectively detect ASO and THI in fruit samples free of derivatization and deep purification. The studies on mechanisms demonstrated that CD intermediates of anionic radical were responsible for the remarkable CL enhancement of ASO or THI. The CL intensity is directly proportional to the fungicide concentration, with the ranges of linearity for ASO and THI being 5–250 μg·L−1 (R2 = 0.9993) and 4–200 μg·L−1 (R2 = 0.9986), respectively, and the corresponding limits of detection (S/N = 3) being 1.61 and 1.33 μg·L−1, respectively. The developed method enables the exploration of the novelly sulphur-targeted CL application based on carbon nanomaterials.

C-reactive protein (CRP) is an acute-phase protein produced by the liver in response to infection and during chronic inflammatory disorders. Systemic inflammation is a major driver of cirrhosis progression from the compensated to the decompensated stage. Previous studies have shown that pentameric CRP (pCRP) to be a weak predictor of disease severity and prognosis in patients with decompensated hepatitis B cirrhosis, with it being only helpful for identifying patients with a higher short-term risk of death under certain conditions. Accumulating evidence indicates that pCRP dissociates to and acts primarily as the monomeric conformation (mCRP) at inflammatory loci, suggesting that mCRP may be a potentially superior disease marker with higher specificity and relevance to pathogenesis. However, it is unknown whether mCRP and anti-mCRP autoantibodies are associated with disease severity, or progression in decompensated hepatitis B cirrhosis. In this study, we evaluated the serum levels of mCRP and anti-mCRP autoantibodies in patients with decompensated cirrhosis of hepatitis B and their association with disease severity and theoretical prognosis. The results showed that patients with high mCRP and anti-mCRP autoantibody levels had more severe liver damage and that coagulation function was worse in patients with high anti-mCRP autoantibodies. Analysis of the correlation between pCRP, mCRP and anti-mCRP autoantibody levels with Model for End-Stage Liver Disease (MELD), Albumin-Bilirubin (ALBI), and Child–Turcotte–Pugh (CTP) prognostic scores showed that mCRP was the most strongly correlated with MELD score, followed by anti-mCRP autoantibodies; conversely, pCRP was not significantly correlated with prognostic score. Therefore, mCRP and anti-mCRP autoantibodies may be more advantageous clinical indicators than pCRP for evaluating the pathological state of decompensated hepatitis B cirrhosis.

Abstract Background The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta‐analysis. Methods Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO‐FC), six‐minute walk distance (6MWD), N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2), were included. Results Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74–37.67), NT‐proBNP (SMD: −0.41, 95% CI: −0.79–0.04), CI (MD: 0.47 L/min/m2, 95% CI: 0.17–0.77) and WHO‐FC (OR: 0.564, 95% CI: 0.457–0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m2, 95% CI: 0.15–0.46) and WHO‐FC (OR: 0.589, 95% CI: 0.376–0.922). Within 6 months of treatment, only the WHO‐FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380–0.993; MD: 0.30 L/min/m2, 95% CI: 0.16–0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO‐FC and NT‐proBNP (MD: 40.87 m, 95% CI: 10.97–70.77; OR: 0.557, 95% CI: 0.440–0.705; SMD: −0.61, 95% CI: −1.17–0.05, respectively). Conclusions Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low‐dosage group. This finding is important for guiding individualized treatments.

Abstract Background Our previous study found that mouse embryonic neural stem cell (NSC)–derived exosomes (EXOs) regulated NSC differentiation via the miR‐9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR‐9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR‐9/Hes1 axis. Methods Immunofluorescence, quantitative real‐time polymerase chain reaction, cell counting kit‐8 assay, wound healing assay, calcein‐acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. Results EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR‐9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR‐9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR‐9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia‐induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. Conclusion NSC‐derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR‐9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia‐induced vascular injury.

Abstract Background Evidence from the Istanbul consensus workshop suggests correlations between morphological parameters and embryo developments. 8-cell embryos are the best blastomere stage on day 3. No good quality evidence exists to support high-quality embryonic selection following blastulation and clinical outcomes. This study aimed to investigate the factors that affect blastocyst formation, blastocyst quality, and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles. Methods This study was a retrospective analysis of 9608 high-quality cleavage-stage embryos from 2987 couples between January 2017 to June 2021, namely 1520 embryos categorized as “812” (8-cell, grade 2, mild fragmentation), 2961 as “821” (8-cell, grade 2, mild asymmetry), 896 as “711” (7-cell, grade 1), and 517 as “911” (9-cell, grade 1) compared with 3714 embryos categorized as “811” (8-cell, grade 1). The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Blastulation rate (BR), available late blastocyst rate (ABR) and high-quality late blastocyst rate (HBR) were secondary outcome measures. Results BR, ABR, and HBR had significant differences among the five groups (P

Abstract Deep‐sea image is of great significance for exploring seabed resources. However, the information of a single image is limited. Besides, deep‐sea image with low contrast and colour distortion further restricts useful feature extraction. To address the issues above, this paper presents a multi‐channel fusion and accelerated‐KAZE (AKAZE) feature detection algorithm for deep‐sea image stitching. First, the authors restore deep‐sea image in LAB colour space and RGB colour space, respectively; in LAB space, the authors use homomorphic filtering in L colour channel, and in RGB space, the authors adopt multi‐scale Retinex with chromaticity preservation algorithm to adjust the colour information. Then, the authors blend two pre‐processed images with dark channel prior weighted coefficient. After that, the authors detect feature points with the AKAZE algorithm and obtain feature descriptors with Boosted Efficient Binary Local Image Descriptor. Finally, the authors match the feature points and warp deep‐sea images to obtain the stitched image. Experimental results demonstrate that the authors’ method generates high‐quality stitched image with minimized seam. Compared with state‐of‐the‐art algorithms, the proposed method has better quantitative evaluation, visual stitching results, and robustness.

BackgroundIdiopathic scoliosis significantly affects the physical and mental health of children and adolescents, with varying prevalence rates in different regions. The occurrence of idiopathic scoliosis is associated with genetic regulation and biochemical factors, but the changes in exosome-derived miRNA profiles among idiopathic scoliosis patients remain unclear. This study aimed to determine the prevalence of idiopathic scoliosis in Yunnan Province, China, and identify key exosome-derived miRNAs in idiopathic scoliosis through a cohort study.MethodsFrom January 2018 to December 2020, a cross-sectional study on idiopathic scoliosis in children and adolescents was conducted in Yunnan Province. A total of 84,460 students from 13 cities and counties in Yunnan Province participated in a scoliosis screening program, with ages ranging from 7 to 19 years. After confirmation through screening and imaging results, patients with severe idiopathic scoliosis and normal control individuals were selected using propensity matching. Subsequently, plasma exosome-derived miRNA sequencing and RT-qPCR validation were performed separately. Based on the validation results, diagnostic performance analysis and target gene prediction were conducted for differential plasma exosome-derived miRNAs.ResultsThe overall prevalence of idiopathic scoliosis in children and adolescents in Yunnan Province was 1.10%, with a prevalence of 0.87% in males and 1.32% in females. The peak prevalence was observed at age 13. Among patients diagnosed with idiopathic scoliosis, approximately 12.8% had severe cases, and there were more cases of double curvature than of single curvature, with thoracolumbar curvature being the most common in the single-curvature group. Sequencing of plasma exosome-derived miRNAs associated with idiopathic scoliosis revealed 56 upregulated and 153 downregulated miRNAs. Further validation analysis confirmed that hsa-miR-27a-5p, hsa-miR-539-5p, and hsa-miR-1246 have potential diagnostic value.ConclusionsWe gained insights into the epidemiological characteristics of idiopathic scoliosis in Yunnan Province and conducted further analysis of plasma exosome-derived miRNA changes in patients with severe idiopathic scoliosis. This study has provided new insights for the prevention and diagnosis of idiopathic scoliosis, paving the way for exploring clinical biomarkers and molecular regulatory mechanisms. However, further validation and elucidation of the detailed biological mechanisms underlying these findings will be required in the future.

ObjectivesThis study aims to investigate the causal relationship between Alzheimer’s Disease (AD) and Diabetic Retinopathy (DR).MethodsEmploying Mendelian Randomization (MR), Generalized Summary-data-based Mendelian Randomization (GSMR), and the MR-Steiger test, this study scrutinizes the genetic underpinnings of the hypothesized causal association between AD and DR, as well as its Proliferative DR (PDR) and Non-Proliferative DR (NPDR) subtypes. Comprehensive data from Genome-Wide Association Studies (GWAS) were analyzed, specifically AD data from the Psychiatric Genomics Consortium (71,880 cases/383,378 controls), and DR, PDR, and NPDR data from both the FinnGen consortium (FinnGen release R8, DR: 5,988 cases/314,042 controls; PDR: 8,383 cases/329,756 controls; NPDR: 3,446 cases/314,042 controls) and the IEU OpenGWAS (DR: 14,584 cases/176,010 controls; PDR: 8,681 cases/204,208 controls; NPDR: 2,026 cases/204,208 controls). The study also incorporated Functional Mapping and Annotation (FUMA) for an in-depth analysis of the GWAS results.ResultsThe MR analyses revealed that genetic susceptibility to AD significantly increases the risk of DR, as evidenced by GWAS data from the FinnGen consortium (OR: 2.5090; 95% confidence interval (CI):1.2102-5.2018, false discovery rate P-value (PFDR)=0.0201; GSMR: bxy=0.8936, bxy_se=0.3759, P=0.0174), NPDR (OR: 2.7455; 95% CI: 1.3178-5.7197, PFDR=0.0166; GSMR: bxy=0.9682, bxy_se=0.3802, P=0.0126), and PDR (OR: 2.3098; 95% CI: 1.2411-4.2986, PFDR=0.0164; GSMR: bxy=0.7962, bxy_se=0.3205, P=0.0129) using DR GWAS from FinnGen consortium. These results were corroborated by DR GWAS datasets from IEU OpenGWAS. The MR-Steiger test confirmed a significant association of all identified instrumental variables (IVs) with AD. While a potential causal effect of DR and its subtypes on AD was identified, the robustness of these results was constrained by a low power value. FUMA analysis identified OARD1, NFYA, TREM1 as shared risk genes between DR and AD, suggesting a potential genetic overlap between these complex diseases.DiscussionThis study underscores the contribution of AD to an increased risk of DR, as well as NPDR and PDR subtypes, underscoring the necessity of a holistic approach in the management of patients affected by these conditions.

In this work, the effect of the addition of γ-polyglutamic acid (γ-PGA) on the rheology, physicochemical properties, and microstructure of fish gelatin (FG) emulsion gel was investigated. Samples of the emulsion gel were evaluated for rheological behavior and stability prior to gelation. The mechanical properties and water-holding capacity (WHC) of the emulsion were determined after gelation. The microstructure of the emulsion gel was further examined using confocal laser scanning microscopy (CLSM). The results indicated a gradual increase in the apparent viscosity and gelation temperature of the emulsion at a higher concentration of γ-PGA. Additionally, frequency scan results revealed that on the addition of γ-PGA, FG emulsion exhibited a stronger structure. The emulsion containing 0.1% γ-PGA exhibited higher stability than that of the control samples. The WHC and gel strength of the emulsion gel increased on increasing the γ-PGA concentration. CLSM images showed that the addition of γ-PGA modified the structure of the emulsion gel, and the droplets containing 0.1% γ-PGA were evenly distributed. Moreover, γ-PGA could regulate the droplet size of the FG emulsion and its size distribution. These findings suggest that the viscoelasticity and structure of FG emulsion gels could be regulated by adjusting the γ-PGA concentration. The γ-PGA-modified FG emulsion gel also exhibited improved rheology and physicochemical properties. The results showed that γ-PGA-modified FG emulsion gel may find potential applications in food, medicine, cosmetics, and other industries.

Background Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. Methods and Results Deep RNA sequencing and quantitative real‐time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P

Tracheal stenosis is a rare but life-threatening disease in preterm infants. Misdiagnosis as congenital tracheal stenosis is common, making surgical management challenging. This report presents a case of a preterm infant with tracheal stenosis and congenital heart malformation treated with ECMO-assisted tracheal resection and end-to-end anastomosis. A male infant was born at 30 weeks of gestation with severe asphyxia, cardiac insufficiency, and pneumonia. Following failed medical treatment, fiberoptic bronchoscopy confirmed mid-tracheal to carinal stenosis. After a 2-week treatment course, ECMO-assisted tracheal resection and end-to-end anastomosis were performed successfully. This case confirms the feasibility of tracheal resection and end-to-end anastomosis in low-weight, preterm infants with tracheal stenosis born at 30 weeks gestation. The utilization of ECMO for oxygenation during surgery provides a clear surgical field and shorter operating time. Surgical intervention may be necessary for neonatal tracheal stenosis depending on the clinical presentation.

Abstract. Background:. Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs (NSAIDs) for treating knee osteoarthritis (OA). We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms (FPC) with loxoprofen sodium cataplasms (LSC) in treating patients with knee OA. Methods:. This is an open-label, non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital. Overall, 250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio. Both medications were administered to patients for 28 days. The primary outcome was the change of pain measured by visual analog scale (VAS) score from baseline to day 28 (range, 0-10 points; higher score indicates worse pain; non-inferiority margin: 1 point; superiority margin: 0 point). There were four secondary outcomes, including the extent of pain relief, the change trends of VAS scores, joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and adverse events. Results:. Among 250 randomized patients (One patient without complete baseline record in the flurbiprofen cataplasms was excluded; age, 62.8 ± 10.5 years; 61.4% [153/249] women), 234 (93.6%) finally completed the trial. In the intention-to-treat analysis, the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior, and also superior to that in the LSC group (differences and 95% confidence interval, 0.414 (0.147-0.681); P

Abstract Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Abstract Mpox (monkeypox) infection cases increased recently in non-Mpox outbreak areas, potentially causing an international threat. The desire to defend against a potential outbreak has led to renewed efforts to develop Mpox vaccines. In this report, mice were immunized with various doses of modified vaccinia virus Ankara (MVA) to evaluate the cross-reactive immune response of MVA immunization against protective antigens of the current monkeypox virus. We demonstrated that MVA induced specific antibodies against protective antigens (A29, A35, B6, M1, H3, and I1), mediating the neutralization abilities against the MVA and the monkeypox virus (MPXV). Moreover, recombinant protective antigens of the MPXV elicited cross-binding and cross-neutralizing activities for MVA. Hence, the MVA induced cross-reactive immune responses, which may guide future efforts to develop vaccines against the recent MPXV. Notably, compared to the other protective antigens, the predominant A29 and M1 antigens mediated higher cross-neutralizing immune responses against the MVA, which could serve as antigen targets for novel orthologous orthopoxvirus vaccine.

BackgroundTo analyze vault effects of crystalline lens rise (CLR) and anterior chamber parameters (recorded by Pentacam) in highly myopic patients receiving implantable collamer lenses (ICLs), which may avoid subsequent complications such as glaucoma and cataract caused by the abnormal vault.MethodsWe collected clinical data of 137 patients with highly myopic vision, who were all subsequent recipients of V4c ICLs between June 2020 and January 2021. Horizontal ciliary sulcus-to-sulcus diameter (hSTS) and CLR were measured by ultrasonic biomicroscopy (UBM), and a Pentacam anterior segment analyzer was used to measure horizontal white-to-white diameter (hWTW), anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), CLR, and postoperative vault (Year 1 and Month 1). The lens thickness (LT) was determined by optical biometry (IOL Master instrument). The predictive model was generated through multiple linear regression analyses of influential factors, such as hSTS, CLR, hWTW, ACD, ACA, ACV, ICL size, and LT. The predictive performance of the multivariate model on vault after ICL was assessed using the receiver operating characteristic (ROC) curve with area under the curve (AUC) as well as the point of tangency.ResultsAverage CLR assessed by UBM was lower than the average value obtained by Pentacam (0.561 vs. 0.683). Bland-Altman analysis showed a good consistency in the two measurement methods and substantial correlation (r = 0.316; P = 0.000). The ROC curve of Model 1 (postoperative Year 1) displayed an AUC of 0.847 (95% confidence interval [CI]: 74.19-95.27), with optimal threshold of 0.581 (sensitivity, 0.857; specificity, 0.724). In addition, respective values for Model 2 (postoperative Month 1) were 0.783 (95% CI: 64.94-91.64) and 0.522 (sensitivity, 0.917; specificity, 0.605).ConclusionCLR and anterior chamber parameters are important determinants of postoperative vault after ICL placement. The multivariate regression model we constructed may serve in large part as a predictive gauge, effectively avoid postoperative complication.

With the rapid development of economic levels, the demand for electricity usage in various industrial sectors has continued to rise. In order to adequately meet the growth in demand for electricity usage at each user end within the power system, accurate forecasting of electricity load is required. This paper uses the K-Means algorithm as the basis, combined with the Canopy algorithm, whose simple and efficient advantages can be used as the initial clustering step for demanding clustering algorithms. The PCA algorithm is used to reduce the dimensionality of the residential multidimensional electricity consumption feature set, and after optimization, the feature vector weights are calculated to obtain the appropriate selection to determine the training and testing samples. The improved K-Means algorithm carries out five clustering tests, and its average accuracy is above 97%. The average relative error is then used as an indicator to compare the algorithm with the time series method, curve extrapolation method, and WKNR method for analysis. The average relative error of the smart grid load forecasting method proposed in this paper is 0.87%, while the average relative errors of the other three algorithms are 1.64%, 1.57%, and 0.93%, respectively. The distribution of relative errors falls less than 1% more than the other methods. It can be seen that the improved K-Means algorithm has higher prediction accuracy and also makes the smart grid load testing platform more practical due to its simple implementation principle.

Introduction Exercise rehabilitation is crucial for promoting the rehabilitation of limb motor function in people who had stroke and is related to a better prognosis. However, the exercise adherence of patients is low, which affects the effect of exercise rehabilitation. This study aims to evaluate the effects of the Innovative Telerehabilitation Enhanced Care Programme (ITECP) on exercise adherence in young and middle-aged patients with haemorrhagic stroke. We hypothesise that patients trained with ITECP will show greater improvement in exercise adherence and muscle strength than patients with routine exercise rehabilitation.Methods and analysis This is a randomised controlled, evaluator-blinded multicentre superiority trial to be implemented at four tertiary grade-A hospitals in eastern, western, northern and central China. Patients in the experimental group will receive ITECP while those in the control group will receive routine exercise rehabilitation. Both groups will receive routine care. The primary outcome measure is exercise adherence, while secondary outcome measures include muscle strength, activities of daily living, exercise self-efficacy, quality of life, rate of exercise-related adverse events and readmission. These will be measured at baseline, predischarge as well as 1 and 3 months postdischarge.Ethics and dissemination The study has obtained ethical approval from the Medical Ethics Committee of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School (2021-381-02). The results will be shared with young and middle-aged patients with haemorrhagic stroke, policy-makers, the general public, as well as academia.Trial registration number Chinese Clinical Trials Registry (ChiCTR 2200066498).

ObjectiveTo evaluate the outcomes of thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) with aberrant right subclavian artery (ARSA).MethodsA retrospective analysis was conducted on patients with TBAD and ARSA who underwent TEVAR between the period of January 2017 and December 2022. Patient demographics, computed tomography angiography (CTA) measurements, surgical procedures, and postoperative outcomes were reviewed.ResultsA total of 9 patients (6 males and 3 females) were included in the study. 4 ARSA were reconstructed, 3 by periscope technique and 1 by in vitro fenestration technique. 3 left subclavian arteries (LSA) were reconstructed, 1 by the chimney technique and 2 by the single-branched stent technique. 2 patients underwent reconstruction of both ARSA and LSA. The overall technical success rate was 100%, with no occurrences of stroke, paraplegia, or mortality within 30 days. 1 patient experienced immediate type Ia endoleak, which resolved after 3 months. 1 patient developed weakness in the right upper limb, while 1 patient presented mild subclavian steal syndrome (SSS); both cases showed recovery during follow-up. The average follow-up duration was 35.6 ± 11.1 months, during which no reinterventions, deaths, or strokes were observed.ConclusionOur limited experience involving 9 patients demonstrates that early and mid-term outcomes of TEVAR for the treatment of TBAD with ARSA are satisfactory.

MicroRNAs (miRNAs) are versatile regulators of pulmonary arterial remodeling in idiopathic pulmonary arterial hypertension (IPAH). We herein aimed to characterize miRNAs in peripheral blood mononuclear cell (PBMC) and plasma exosomes, and investigate specific miRNA expression in pulmonary artery cells and lung tissues in IPAH. A co-dysregulated miRNA was identified from the miRNA expression profiles of PBMC and plasma exosomes in IPAH. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the potential function of differentially expressed miRNAs. Real-time quantitative reverse transcription polymerase chain reaction was used to validate the expression of specific miRNAs in hypoxia-induced pulmonary microvascular endothelial cells (PMECs), pulmonary artery smooth muscle cells (PASMCs), pericyte cells (PCs), and lung tissues of patients with IPAH and rats. Finally, the miRNA-mRNA mechanisms of miR-122-5p were predicted. MiR-122-5p was the only co-upregulated miRNA in PBMC and plasma exosomes in patients with IPAH. Functional analysis of differentially expressed miRNAs revealed associations with the GO terms “transcription, DNA-templated,” “cytoplasm,” and “metal ion binding” in both PBMC and plasma exosomes, KEGG pathway MAPK signaling in PBMC, and KEGG-pathway human papillomavirus infection in plasma exosomes. Hypoxic PMECs and PCs, lung tissue of patients with IPAH, and rats showed increased expression of miR-122-5p, but hypoxic PASMCs showed decreased expression. And miR-122-5p mimics and inhibitor affected cell proliferation. Finally, miR-122-5p was found to potentially target DLAT (in lung tissue) and RIMS1 (in PMECs) in IPAH. According to the dual-luciferase assay, miR-122-5p bound to DLAT or RIMS1. In studies, DLAT imbalance was associated with cell proliferation and migration, RIMS1 is differentially expressed in cancer and correlated with cancer prognosis. Our findings suggest that the miR-122-5p is involved in various biological functions in the adjacent vascular wall cells in IPAH.

Telecommunication network operations and maintenance is a basic and critical work for communications service providers (CSP).At present, there is little public operations and maintenance information of CSP.In addition, it is lack of effective evaluation model of telecommunication network operations and maintenance.A multi-dimensional evaluation model of telecommunication network operations and maintenance was proposed, which took abalanced score card as a basis and was combined with long-term operations and maintenance work and research practice.The model was verified by applying different types of CSP, including international large CSP, innovative CSP, and high-growth CSP.

Abstract Background Oocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated. Results To decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A. Conclusions Our findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of “coughing and vomiting for 6 days”. A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.

Purpose: Given the high incidence and mortality rates of colorectal cancer (CRC) and the inadequacy of existing treatments for many patients, this study aimed to explore the potential of Capping Actin Protein (CAPG), a protein involved in actin-related movements, as a novel therapeutic target for CRC. Methods: Bioinformatic analysis of gene expression was conducted using the UALCAN website. Cell proliferation was measured using the CCK-8 kit. Cell cycle, apoptosis, and ferroptosis were analyzed using flow cytometry. Tumorigenesis was evaluated by the subcutaneous inoculation of CRC cells into BALB/c nude female mice. Differentially expressed genes and signaling pathways were identified using RNA sequencing. Results: CAPG was significantly overexpressed in human CRC tissues and its upregulation was correlated with poor overall survival. CAPG knockdown led to notable inhibition of CRC cells in vitro and in vivo. Interference with CAPG blocked the cell cycle at the G1 phase and triggered apoptosis and ferroptosis by upregulating the P53 pathway in CRC cells. Conclusion: CRC patients with higher CAPG levels have a poorer prognosis. CAPG inhibits apoptosis and ferroptosis, while promoting CRC cell proliferation by repressing the P53 pathway. Our study suggests that CAPG may be a potential therapeutic target for CRC prognosis and treatment.

ObjectiveA multitude of observational studies have underscored a substantial comorbidity between COVID-19 and epilepsy. This study was aimed at establishing a conclusive causal link between these two conditions.MethodsWe employed Mendelian randomization (MR) to evaluate the causal link between COVID-19 and epilepsy, as well as its focal and generalized subtypes. The GWAS for epilepsy and its subtypes database were abstracted from both FinnGen consortium and ILAE. Additionally, we leveraged functional mapping and annotation (FUMA) to integrate information from genome-wide association studies (GWAS) results.ResultsThe MR analyses revealed that genetic liability to COVID-19 infection conferred a causal effect on epilepsy [FinnGen: OR: 1.5306; 95% confidence interval (CI): 1.1676–2.0062, PFDR (false discovery rate) = 0.0076; ILAE: OR: 1.3440; 95% CI: 1.0235–1.7649, PFDR = 0.0429], and generalized epilepsy (FinnGen: OR: 2.1155; 95% CI: 1.1734–3.8139, PFDR = 0.0327; ILAE: OR: 1.1245; 95% CI: 1.0444–1.2108, PFDR = 0.0114). Genetic liability to COVID-19 hospitalization conferred a causal effect on epilepsy (FinnGen: OR: 1.0934; 95% CI: 1.0097–1.1841, PFDR = 0.0422; ILAE: OR: 1.7381; 95% CI: 1.0467–2.8862, PFDR = 0.0451), focal epilepsy (ILAE: OR: 1.7549; 95% CI: 1.1063–2.7838, PFDR = 0.0338), and generalized epilepsy (ILAE: OR: 1.1827; 95% CI: 1.0215–1.3693, PFDR = 0.0406). Genetic liability to COVID-19 severity conferred a causal effect on epilepsy (FinnGen consortium: OR: 1.2454; 95% CI: 1.0850–1.4295, PFDR = 0.0162; ILAE: OR: 1.2724; 95% CI: 1.0347–1.5647, PFDR = 0.0403), focal epilepsy (FinnGen: OR: 1.6818; 95% CI: 1.1478–2.4642, PFDR = 0.0231; ILAE: OR: 1.6598; 95% CI: 1.2572–2.1914, PFDR = 0.0054), and generalized epilepsy (FinnGen: OR: 1.1486; 95% CI: 1.0274–1.2842, PFDR = 0.0335; ILAE: OR: 1.0439; 95% CI: 1.0159–1.0728, PFDR = 0.0086). In contrast, no causal linkage of epilepsy on COVID-19 was observed. Further, FUMA analysis identified six overlapping genes, including SMEK2, PNPT1, EFEMP1, CCDC85A, VRK2, and BCL11A, shared between COVID-19 and epilepsy. Tissue-specific expression analyses revealed that the disease-gene associations of COVID-19 were significantly enriched in lung, ovary, and spleen tissue compartments, while being significantly enriched in brain tissue for epilepsy.ConclusionOur study demonstrates that COVID-19 can be a contributing factor to epilepsy, but we found no evidence that epilepsy contributes to COVID-19.

Pericytes play an indispensable role in various organs and biological processes, such as promoting angiogenesis, regulating microvascular blood flow, and participating in immune responses. Therefore, in this review, we will first introduce the discovery and development of pericytes, identification methods and functional characteristics, then focus on brain pericytes, on the one hand, to summarize the functions of brain pericytes under physiological conditions, mainly discussing from the aspects of stem cell characteristics, contractile characteristics and paracrine characteristics; on the other hand, to summarize the role of brain pericytes under pathological conditions, mainly taking ischemic stroke as an example. Finally, we will discuss and analyze the application and development of pericytes as therapeutic targets, providing the research basis and direction for future microvascular diseases, especially ischemic stroke treatment.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein–protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes (ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future.

Abstract Through a review of previous studies, this paper analysed the epidemiological characteristics and attempts to determine the various trends of road traffic injuries (RTIs) in China before and after the coronavirus disease 2019 (COVID-19). This paper proposed effective measures and suggestions for responding to RTIs in China. Moreover, this paper aimed to provide some references for studies on RTIs in the future. According to a reference review, 50 articles related to RTIs were published and viewed in the China National Knowledge Infrastructure (CNKI), Wanfang database, Weipu (VIP) database and PubMed/MEDLINE database. Articles were selected according to the exclusion and inclusion criteria and then classified and summarized. Regarding cases, RTIs in China were highest in summer, autumn, and in rural areas and lowest in February. Men, elderly individuals and people living in rural areas were more susceptible to RTIs. In addition, thanks to effective and proactive policies and measures, the number of RTIs and casualties in China has substantially decreased, while there has been a growing number of traffic accidents along with the increase in nonmotor vehicles. However, it is worth noting that the number of RTIs obviously fell during the COVID-19 pandemic due to traffic lockdown orders and home quarantine policies. Nevertheless, accidents related to electric bicycles increased unsteadily because of the reduction in public transportation use at the same time. The factors that cause RTIs in China can be divided into four aspects: human behaviours, road conditions, vehicles and the environment. As a result, measures responding to RTIs should be accordingly proposed. Moreover, the road traffic safety situation in developing countries was more severe than that in developed countries. RTIs in China showed a downward trend attributed to road safety laws and various policies, and the downward trend was more significant during the COVID-19 pandemic owing to traffic lockdowns and home quarantine measures. It is urgent and necessary to promote road traffic safety, reduce injuries, and minimize the burden of injuries in developing countries.

Abstract Background The WHO recommends daily use of micronutrient powder for infants and toddlers at risk of micronutrient deficiencies in low-and-middle-income countries. China has established a micronutrient powder distribution program in many rural townships and villages, yet adherence to micronutrient powder remains suboptimal; a little is known about the behavioral inputs that may influence adherence. This study examines direct and indirect behavioral inputs in micronutrient powder adherence among caregivers in rural western China following the Integrated Behavioral Model (IBM) framework. Methods Cross-sectional data were collected from April to May 2019 among 958 caregivers of children aged 6 to 24 months in six counties. Data were collected on micronutrient powder adherence behavior, direct behavioral inputs (knowledge and skills, intention, salience, environmental constraints, and habits), and indirect behavioral inputs (attitudes, perceived social norms, and personal agency). Structural equation modeling (SEM) adjusted for sociodemographic covariates was used to evaluate the IBM framework. Results Mean micronutrient powder adherence in the previous seven days was 53.02%, and only 22.86% of caregivers consistently fed micronutrient powder from the start of micronutrient powder distribution at six months of age. The SEM model revealed small- to medium-sized effects of salience (β = 0.440, P

Three inactivated enterovirus A71 (EV-A71) vaccines have been widely vaccinated among children in the targeted age group in mainland China since mid-2016. However, comprehensive virological surveillance of hand, foot and mouth disease (HFMD) over multiple years after the use of EV-A71 vaccines has rarely been conducted. Using long-term data extracted from the Public Health and Clinical Center of Chengdu, we described the clinical, aetiological, and epidemiological characteristics of HFMD inpatients after the use of EV-A71 vaccines from 2017 through 2022. A total of 5115 patients were selected for analysis with a male-to-female ratio of 1.63:1 and were mostly under 5 years of age (97.6%). Among these cases, 4.3% presented with severe symptoms, and 4.1% of severe cases experienced significant complications. EV-A71 was no longer the major serotype for laboratory-confirmed HFMD, responsible for 15.6% of severe cases and 1.2% of mild cases. A significant downwards trend of EV-A71 infections was observed after the use of EV-A71 vaccines (P for trend < 0.001). Coxsackievirus A6 was the predominant pathogen, accounting for 63.5% of mild cases and 36.2% of severe cases. Coxsackievirus A10 (CV-A10) and A16 were sporadically detected, and an upwards trend was observed in the proportion of CV-A10 infections. This study provides baseline molecular epidemiology for the evaluation of EV-A71 vaccination impact and potential serotype replacement based on HFMD inpatients. Additional nationwide and population-based epidemiologic and serologic studies are essential to elucidate HFMD dynamics after the use of EV-A71 vaccines, and to inform public health authorities to introduce optimized intervention strategies.

Abstract Background Our previous study showed that circular RNA-gamma-secretase-activating protein (circGSAP) was down-regulated in pulmonary microvascular endothelial cells (PMECs) in response to hypoxia, and regulated the cell cycle of PMECs via miR-942-5p sponge in pulmonary hypertension (PH). However, the mechanism whether circGSAP affects the dysfunction of PEMCs through other microRNAs (miRNAs) remains largely unknown. Therefore, we aimed to demonstrate the underlying mechanisms of circGSAP regulating PMECs dysfunction by absorbing other miRNAs to regulate target genes in idiopathic pulmonary arterial hypertension (IPAH). Methods Quantitative real-time polymerase chain reaction, immunofluorescence staining, Cell Counting Kit-8, Calcein-AM/PI staining, Transwell assay, dual-luciferase reporter assay, and ELISA were used to elucidate the roles of circGSAP. Results Here we showed that plasma circGSAP levels were significantly decreased in patients with IPAH and associated with poor outcomes. In vivo, circGSAP overexpression improved survival, and alleviated pulmonary vascular remodeling of monocrotaline-induced PH (MCT-PH) rats. In vitro, circGSAP overexpression inhibited hypoxia-induced PMECs proliferation, migration and increased mortality by absorbing miR-27a-3p. BMPR2 was identified as a miR-27a-3p target gene. BMPR2 silencing ameliorated the effect of the miR-27a-3p inhibitor on PMECs proliferation,migration and mortality. The levels of BMPR2 were upregulated in circGSAP-overexpressed PMECs and lung tissues of MCT-PH rats. Conclusion Our findings demonstrated that circGSAP alleviated the dysfunction of PMECs via the increase of BMPR2 by competitively binding with miR-27a-3p, and mitigated pulmonary vascular remodeling of MCT-PH rats, providing potential therapeutic strategies for IPAH.

Abstract The association between blood eosinophil (EOS) counts and arterial/venous thrombosis is unclear. We aim to explore whether EOS count is a risk factor for thrombosis. We searched several databases and preprint platforms using core terms ‘eosinophil’, ‘myocardial infarction’, ‘ischemic stroke’, and ‘venous thromboembolism’ (VTE), among others. Studies comparing the odds ratios (ORs) or risk ratios (RRs) of EOSs with the abovementioned diseases were eligible. Overall, 22 studies were included. A high EOS count was associated with acute coronary artery thrombosis events (OR: 1.23, 95% CI: 1.15–1.32), short‐term cerebral infarction and mortality (RR: 2.87, 95% CI: 1.49–5.51). The short‐term risk of VTE was more common in patients with EOS‐related diseases (RR: 6.52, 95% CI: 2.42–17.54). For coronary artery disease, a high EOS count was a protective factor against 6‐month to 1‐year mortality (RR: 0.56, 95% CI: 0.45–0.69) but was associated with long‐term mortality (RR: 1.64, 95% CI: 1.25–2.14). Therefore, we conclude that for coronary artery thrombosis, EOS count is not associated with AMI events in general population. It may be associated with NSTEMI and STEMI in CAD patients, but more studies are needed to confirm this. In addition, EOS count is associated with an increased risk of both short‐ and long‐term mortality but is not predictive of the composite endpoints. For cerebral artery thrombosis, EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short‐term prognosis. For VTEs, EOS count was a risk factor for some patients, especially those with acute‐phase EOS‐related diseases.

Background: PTSD (Post-traumatic stress disorder, PTSD) had a great impact on health care workers during the COVID-19 (Corona Virus Disease 2019, COVID-19). Better knowledge of the prevalence of PTSD and its risk factors is a major public health problem. This study was conducted to assess the prevalence and important risk factors of PTSD among medical staff during the COVID-19. Methods: The databases were searched for studies published during the COVID-19, and a PRISMA (preferred reporting items for systematic review and meta-analysis) compliant systematic review (PROSPERO-CRD 42021278970) was carried out to identify articles from multiple databases reporting the prevalence of PTSD outcomes among medical staff. Proportion random effect analysis, I2 statistic, quality assessment, subgroup analysis, and sensitivity analysis were carried out. Results: A total of 28 cross-sectional studies and the PTSD results of doctors and nurses were summarized from 14 and 27 studies: the prevalences were 31% (95% CI [confidence interval, CI]: 21%–40%) and 38% (95% CI: 30%–45%) in doctors and nurses, respectively. The results also showed seven risks (p

Summary: Background: Pyrimidine nucleotides fuel the growth of colorectal cancer (CRC), making their associated proteins potential targets for cancer intervention. Uridine-Cytidine Kinase Like-1(UCKL1) is an enzyme involved in the pyrimidine salvage pathway. It is highly expressed in multiple cancers. But the function and underlying mechanism of UCKL1 in CRC are yet to study. Methods: Large-scale genomic analysis was performed to search for potential CRC players related to pyrimidine metabolism. The function of UCKL1 in CRC were examined by RNA interference coupled with in vitro and in vivo assays. GSH/GSSG assay, NADP+ assay, ROS, and Lipid peroxidation assays were performed to check the function of UCKL1 in ferroptosis. Metabolomics analyses, RNA sequencing, western blotting, and rescue assays were done to reveal the underlying mechanisms of UCKL1. Xenograft mouse model was used to examine the therapeutic potential of UCKL1 as a target in combination with other ferroptosis inducers. Findings: UCKL1 was identified to repress ferroptosis in CRC cells. It was highly expressed in CRC. It regulated CRC cells proliferation and migration. Downregulation of UCKL1 led to enhanced tumour lipid peroxidation. Intriguingly, UCKL1 reduction-mediated ferroptosis was not related to its role in catalyzing uridine monophosphate (UMP) and cytidine monophosphate (CMP) synthesis. Instead, UCKL1 stabilized Nrf2, which in turn promoted the expression of SLC7A11, a classical repressor of ferroptosis. Moreover, downregulation of UCKL1 sensitized CRC cells to GPX4 inhibitors in vitro and in vivo. Interpretation: Our study demonstrates that UCKL1 plays a non-canonical role in repressing ferroptosis through a UCKL1-Nrf2-SLC7A11 axis in CRC cells. Combinatorial strategy in targeting ferroptosis by depletion of UCKL1 and application of GPX4 inhibitors may serve as a new effective method for CRC treatment. Funding: This study was supported in part by fund from National Natural Science Foundation of China (Grant No. 31970674 to PY), by the Basic and Applied Basic Research Program of Guangdong Province (Grant No. 2023A1515030245 to KL), by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), and by National Key Clinical Discipline.

Abstract The biological roles of epithelial–mesenchymal transition (EMT) in the pathogenesis of radiation‐induced lung injury (RILI) have been widely demonstrated, but the mechanisms involved have been incompletely elucidated. N6‐methyladenosine (m6A) modification, the most abundant reversible methylation modification in eukaryotic mRNAs, plays vital roles in multiple biological processes. Whether and how m6A modification participates in ionizing radiation (IR)‐induced EMT and RILI remain unclear. Here, significantly increased m6A levels upon IR‐induced EMT are detected both in vivo and in vitro. Furthermore, upregulated methyltransferase‐like 3 (METTL3) expression and downregulated α‐ketoglutarate‐dependent dioxygenase AlkB homolog 5 (ALKBH5) expression are detected. In addition, blocking METTL3‐mediated m6A modification suppresses IR‐induced EMT both in vivo and in vitro. Mechanistically, forkhead box O1 (FOXO1) is identified as a key target of METTL3 by a methylated RNA immunoprecipitation (MeRIP) assay. FOXO1 expression is downregulated by METTL3‐mediated mRNA m6A modification in a YTH‐domain family 2 (YTHDF2)‐dependent manner, which subsequently activates the AKT and ERK signaling pathways. Overall, the present study shows that IR‐responsive METTL3 is involved in IR‐induced EMT, probably by activating the AKT and ERK signaling pathways via YTHDF2‐dependent FOXO1 m6A modification, which may be a novel mechanism involved in the occurrence and development of RILI.

Summary: AMP-activated protein kinase (AMPK) is a critical cellular energy sensor at the interface of metabolism and cancer. However, the role of AMPK in carcinogenesis remains unclear. Here, through analysis of the TCGA melanoma dataset, we found that PRKAA2 gene that encodes the α2 subunit of AMPK is mutated in ∼9% of cutaneous melanomas, and these mutations tend to co-occur with NF1 mutations. Knockout of AMPKα2 promoted anchorage-independent growth of NF1-mutant melanoma cells, whereas ectopic expression of AMPKα2 inhibited their growth in soft agar assays. Moreover, loss of AMPKα2 accelerated tumor growth of NF1-mutant melanoma and enhanced their brain metastasis in immune-deficient mice. Our findings support that AMPKα2 serves as a tumor suppressor in NF1-mutant melanoma and suggest that AMPK could be a therapeutic target for treating melanoma brain metastasis.

Conductive hydrogels, characterized by their excellent conductivity and flexibility, have attracted widespread attention and research in the field of flexible wearable sensors. This paper reviews the application progress, related challenges, and future prospects of conductive hydrogels in flexible wearable sensors. Initially, the basic properties and classifications of conductive hydrogels are introduced. Subsequently, this paper discusses in detail the specific applications of conductive hydrogels in different sensor applications, such as motion detection, medical diagnostics, electronic skin, and human–computer interactions. Finally, the application prospects and challenges are summarized. Overall, the exceptional performance and multifunctionality of conductive hydrogels make them one of the most important materials for future wearable technologies. However, further research and innovation are needed to overcome the challenges faced and to realize the wider application of conductive hydrogels in flexible sensors.

Abstract Background and objective End-tidal PCO2 (PetCO2) patterns during exercise testing as well as ventilatory equivalents for CO2 have been reported for different pulmonary vascular diseases but seldomly for the significant differences in exercise response depending on the etiology of pulmonary hypertension. We aimed to compare PetCO2 change pattern in IPAH and CTEPH with varying severity during incremental cardiopulmonary exercise testing (CPET). Methods 164 IPAH patients and 135 CTEPH patients referred to Shanghai Pulmonary Hospital between 2012 and 2019 were retrospectively recruited into the study. All patients performed CPET and also underwent right-heart catheterization (RHC). Forty-four healthy subjects also performed CPET and were included as controls. Results PetCO2 was significantly lower in IPAH and CTEPH patients as compared to normal subjects. Moreover, the PetCO2 did not rise, in fact fell from rest to anaerobic threshold (AT), then further decreased until peak in both IPAH and CTEPH. PetCO2 value at rest, unloaded, AT and peak were proportionately reduced as the World Health Organization functional class (WHO-Fc) increased in both IPAH and CTEPH patients. The PETCO2 in IPAH patients had significant differences during all phases of exercise between WHO-Fc I-II and III-IV subgroup. CTEPH also demonstrated significant difference except for PetCO2 at peak. PetCO2 values were significantly higher in IPAH during all phases of exercise as compared to CTEPH patients (all P

Abstract Background Aberrant expression of microRNAs (miRNAs) has been associated with the pathogenesis of pulmonary hypertension (PH). It is, however, not clear whether miRNAs are involved in estrogen rescue of PH. Methods Fresh plasma samples were prepared from 12 idiopathic pulmonary arterial hypertension (IPAH) patients and 12 healthy controls undergoing right heart catheterization in Shanghai Pulmonary Hospital. From each sample, 5 μg of total RNA was tagged and hybridized on microRNA microarray chips. Monocrotaline‐induced PH (MCT‐PH) male rats were treated with 17β‐estradiol (E2) or vehicle. Subgroups were cotreated with estrogen receptor (ER) antagonist or with antagonist of miRNA. Results Many circulating miRNAs, including miR‐21‐5p and miR‐574‐5p, were markedly expressed in patients and of interest in predicting mean pulmonary arterial pressure elevation in patients. The expression of miR‐21‐5p in the lungs was significantly upregulated in MCT‐PH rats compared with the controls. However, miR‐574‐5p showed no difference in the lungs of MCT‐PH rats and controls. miR‐21‐5p was selected for further analysis in rats as E2 strongly regulated it. E2 decreased miR‐21‐5p expression in the lungs of MCT‐PH rats by ERβ. E2 reversed miR‐21‐5p target gene FilGAP downregulation in the lungs of MCT‐PH rats. The abnormal expression of RhoA, ROCK2, Rac1 and c‐Jun in the lungs of MCT‐PH rats was inhibited by E2 and miR‐21‐5p antagonist. Conclusions miR‐21‐5p level was remarkably associated with PH severity in patients. Moreover, the miR‐21‐5p/FilGAP signaling pathway modulated the protective effect of E2 on MCT‐PH through ERβ.