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Purpose: The European Working Group on Sarcopenia in Older People (EWGSOP) revised the consensus in 2018, including that using computed tomography (CT) imaging of the lumbar third vertebra (L3) for the evaluation of muscle mass. However, there is currently discrepancy and confusion in the application of specific cross-sectional and cutoff values for L3. This study aimed to standardize the diagnosis of low muscle mass using L3-CT., Materials and Methods: This study included patients who underwent radical gastrectomy for gastric cancer between July 2014 and February 2019. Sarcopenia factors were measured preoperatively. Patients were followed up to obtain actual clinical outcomes. We used the cutoff values obtained based on the inferior aspect of L3-CT images to diagnose sarcopenia in three aspects, respectively. Univariate and multivariate analyses were used to compare long-term and short-term postoperative prognostic differences., Results: Sarcopenia was found to be an independent risk factor for postoperative complications and overall survival in patients with all three diagnoses of sarcopenia. According to the multivariate model for predicting postoperative complications, patients with inferior-L3 sarcopenia (n = 154,13.8%) had a greater odds ratio (OR) than patients with superior-L3 sarcopenia (n = 220,19.7%) or transverse-L3 sarcopenia (n = 194,17.4%) did (OR, inferior sarcopenia vs. superior sarcopenia, transverse sarcopenia, 2.030 vs. 1.608, 1.679). Furthermore, patients with inferior-L3 sarcopenia had the highest hazard ratio (HR) (HR, inferior sarcopenia vs. superior sarcopenia, transverse sarcopenia, 1.491 vs. 1.408, 1.376) in the multivariate model for predicting overall survival., Conclusion: We recommend that when diagnosing low muscle mass using L3-CT, the intercepted cross section should be uniform and consistent with the aspect on which the cutoff value is based., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Wenzhou Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Anxiety is known to significantly impair cognitive function, particularly attentional control. While exercise has been demonstrated to alleviate these cognitive deficits, the precise neural mechanisms underlying these effects remain poorly understood. This study examines the effects of exercise on attentional control in individuals with high trait anxiety, based on attentional control theory, which suggests that such individuals have reduced top-down attention. Thirty-eight participants were randomly assigned to either an exercise group or a reading group. The exercise group engaged in 30 min of moderate-intensity cycling, while the reading group spent 30 min reading quietly. In Experiment 1, goal-directed attention was assessed using a cue-object paradigm, and in Experiment 2, inhibitory control was evaluated through a visual search task. EEG data indicated that the exercise group exhibited significantly larger Pd components in both experiments, suggesting enhanced attentional focus and improved inhibition of distractors. These findings suggest that aerobic exercise enhances top-down attentional processes, particularly goal-directed attention and distractor inhibition, offering potential as an intervention for individuals with high trait anxiety., Competing Interests: Declarations. Ethics approval and consent to participate: The experiment adhered to ethical guidelines, with all participants providing informed consent prior to participation, and they were compensated for their involvement upon completing the study. This study was approved by the Institutional Research Ethics Committee of Wuhan Sports University (2023016). Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Monitoring perioperative tissue perfusion is crucial in clinical anesthesia to protect organs and ensure patient safety. Indicators like hemodynamic parameters, tissue metabolism, and microcirculation markers are used for assessment. Studies show intraoperative hypotension negatively impacts outcomes, though blood pressure alone may not reflect tissue perfusion accurately. Cardiac output is a more direct measure, with adequate levels generally indicating good perfusion. However, some conditions cause adequate cardiac output but inadequate perfusion. Non-quantitative markers like skin color and temperature, and quantitative indicators like tissue oxygen saturation and laser Doppler flowmetry, help assess microcirculation but can't fully evaluate systemic perfusion. Near-Infrared Spectroscopy (NIRS) monitors tissue oxygen metabolism, reflecting oxygen supply and consumption balance. Central venous oxygen saturation offers a better systemic overview but may not always indicate good perfusion, especially in sepsis. Lactic acid levels closely correlate with tissue perfusion and outcomes, with dynamic changes being more indicative than single measurements. Effective monitoring requires evaluating both macro- and microcirculation states and systemic metabolic levels to ensure optimal outcomes. Combining these measures provides a more accurate assessment of tissue perfusion and patient prognosis., Competing Interests: Declarations. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2025. The Author(s).)

Background: A. muciniphila (AKK) has attracted extensive research interest as a potential next-generation probiotics, but its role in intestinal pathology is remains unclear. Herein, this study was conducted to investigate the effects of A. muciniphila DSM 22,959 on growth performance, intestinal barrier function, microecology and inflammatory response of weaned piglets stimulated by dextran sulfate sodium salt (DSS)., Method: Twenty-four Duroc × Landrace × Yorkshire (DLY) weaned piglets used for a 2 × 2 factorial arrangement of treatments were divided into four groups with six piglets in each group. From 1 to 15 d, the CA and DA groups were orally fed with 1.0 × 10 11 colony-forming units A. muciniphila per day, while the CON and DCON groups were received gastric infusion of anaerobic sterile saline per day. The pigs were orally challenged (DCON, DA) or not (CON, CA) with DSS from day 9 to the end of the experiment and slaughtered on day 16., Results: Presence of A. muciniphila in DSS-challenged weaned pigs resulted in numerically increased diarrhea rate, blood neutrophilic granulocyte, serum C-reactive protein and immunoglobulin M levels, and numerically reduced final weight, average daily feed intake and average daily gain. The decrease in intestinal villus height, villous height: crypt depth ratio and digestibility was accompanied by lower expression of ZO1, ZO2, Claudin1, DMT1, CAT1, SGLT1 and PBD114 genes, as well as decreased enzyme activities of intestinal alkaline phosphatase, lactase, sucrase and maltase of piglets in DA group compared to piglets in DCON group. The abundance of Bifdobacterium, Lactobacillus, A. muciniphila, Ruminococcus gnavus was numerically higher in digesta of pigs in DA group than those in DCON group. The inflammatory responses of piglets were dramatically changed by the simultaneous presence of A. muciniphila and DSS: expression level of IL17A, IL17F, IL23, RORγt, Stat3 was elevated in DA pigs compared to the other pig groups., Conclusions: Our result showed that the oral A. muciniphila aggravates DSS-induced health damage of weaned piglet, which may attribute to the deteriorating intestinal morphology, dysbiosis of microbiota and inflammatory response disorders., Competing Interests: Declarations. Ethics approval and consent to participate: All animal procedure were approved by the Committee on Animal Care Advisory of Sichuan Agricultural University, Chengdu, China (approval no. SICAU-2023-10). The present research was carried out in compliance with the guidelines for the care and use of laboratory animals (2017 Revision) formulated by the State Council of China. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: Neuroendocrine cervical carcinoma (NECC) is a rare but highly aggressive tumor. The clinical management of NECC follows neuroendocrine neoplasms and cervical cancer in general. However, the diagnosis and prognosis of NECC remain dismal. The aim of this study was to identify a specific protein signature for the diagnosis of NECC., Methods: Protein and gene expression data for NECC and other cervical cancers were retrieved or downloaded from self-collected samples or public resources. Eleven machine-learning algorithms were packaged into 66 combinations, of which we selected the optimal algorithm, including randomForest, SVM-RFE, and LASSO, to select key NECC specific dysregulated proteins (kNsDEPs). The diagnostic effect of kNsDEPs was validated by a set of predictive models and immunohistochemical staining method. The dysregulation patterns of kNsDEPs were further investigated in other neuroendocrine carcinomas., Results: Our results showed that NECC displays distinctive biological characteristics, such as HPV18 infection, and exhibits unique molecular features, particularly an enrichment in cytoskeleton-related functions. Furthermore, secretagogin (SCGN), adenylyl cyclase-associated protein 2 (CAP2), and calcyclin-binding protein (CACYBP) were identified as kNsDEPs. These kNsDEPs play a central role in cytoskeleton protein binding and showcase robust diagnostic ability and specificity for NECC. Moreover, the concurrent upregulation of SCGN and CACYBP, along with the downregulation of CAP2, represents a unique feature of NECC, distinguishing it from other neuroendocrine carcinomas., Conclusions: This study uncovers the significance of kNsDEPs and elucidates their regulated networks in the context of NECC. It highlights the pivotal role of kNsDEPs in NECC diagnosis, thus offering promising prospects for the development of diagnostic biomarkers for NECC., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in line with the principles of Declaration of Helsinki. The research protocol was approved by the ethical committee for human experimentation of East China Normal University Wuhu Affiliated Hospital (The Second People’s Hospital of Wuhu City) (Approval number 2024-KY-009) and Anhui Normal University (Approval number AHNU-ET2023080). All patients included in this research have granted written informed consent for the use of their data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: To assess the therapeutic effects of mesenchymal stem cell (MSC)-derived exosome therapy on periodontal regeneration and identify treatment factors associated with enhanced periodontal regeneration in recent preclinical studies., Methods: Searches were conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases until October 10, 2024. A risk of bias (ROB) assessment was performed using the SYRCLE tool. Osteogenic-related parameters were used as the primary outcome measures., Results: In total, 1360 articles were identified, of which 17 preclinical studies were based on MSC-derived exosome therapy, and they demonstrated a beneficial effect on BV/TV (SMD = 13.99; 95% Cl = 10.50, 17.48; p < 0.00001), CEJ-ABC (SMD = -0.22; 95% Cl = -0.31, -0.13; p < 0.00001), BMD (SMD = 0.29; 95% Cl = 0.14, 0.45; p = 0.0002), and Tp.Sp (SMD = -0.08; 95% Cl= -0.15, -0.02; p = 0.02) compared with the control group. However, no significant differences were observed in Tp.Th (SMD = 0.03; 95% CI = 0.00, 0.07; p = 0.09) between the exosome-treated group and control group. Additionally, subgroup analysis indicated that preconditioned exosomes (p = 0.03) significantly improved BV/TV. In contrast, there were no significant differences in the enhancement of BV/TV with respect to the application method (p = 0.29), application frequency (p = 0.10), treatment duration (p = 0.15), or source of MSCs (p = 0.31)., Conclusions: MSC-derived exosomes show great promise for enhancing the quality of periodontal regeneration. However, more standardized and robust trials are needed to reduce heterogeneity and bias across studies and to confirm the therapeutic parameters associated with the enhancement of periodontal regeneration by MSC-derived exosomes., Registration: CRD42024546236., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: To analyze the molecular epidemiological characteristics of influenza viruses in influenza-like cases in Chongqing Hi-Tech Zone, China, to provide data support and a scientific basis for optimizing influenza prevention and control strategies in the region., Materials and Methods: A retrospective analysis was conducted on the molecular epidemiological characteristics of influenza viruses in influenza-like cases at a hospital in Chongqing Hi-Tech Zone from 2021 to 2024. Colloidal gold detection of viral antibodies, fluorescent PCR detection of nucleic acids, and gene sequencing were used to identify the different subtypes., Results: Among 39,986 ILI specimens tested using the immunocolloid gold method, 6,616 influenza viruses were detected, with a detection rate of 16.54%. Infections included 4,464 influenza A viruses (67.50%), 2,033 influenza B viruses (30.73%), and 119 co-infections of influenza A and B viruses (1.77%).In this region, H3N2 was the predominant subtype of influenza A, and Victoria was the main subtype of influenza B., Conclusion: Influenza epidemics in the winter and spring seasons in Chongqing Hi-Tech Zone were predominantly caused by influenza A, with influenza B also circulating. Influenza A strains were mainly H3N2, while influenza B strains were primarily Victoria., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: To assess the clinical utility of PCA3 in the diagnostic accuracy, the correlation between PCA3 and biopsy or pathological characteristics and the performance of PCA3 to reduce the unnecessary biopsies in Chinese population., Methods: A prospective study including patients with indication of prostate biopsies from 4 centers was conducted. All patients underwent PCA3 urine tests and prostate biopsies. The PCA3 score was analyzed by PCA3 gene expression Detection Kit (Fluorescent RT-PCR) (York biotech, Cat.#YDM-B01, China). Base model (clinical information) and PCA3 model (PCA3 scores and clinical information) were constructed via multivariate logistic regression. Discrimination, calibration and decision curve analysis were evaluated., Results: In 1117 patients, 587 men with positive biopsy results had higher median PCA3 scores than those with negative biopsy results (p < 0.001). PCA3 scores had a greater area under the curve (AUC) than tPSA, %fPSA and PSAD in all PSA levels or PSA gray zone (4-10 ng/ml). Men with biopsy Gleason score < 7 had lower median PCA3 scores than those with Gleason score ≥ 7 (p = 0.016). In radical prostatectomy specimens, PCA3 scores were significantly associated with high-grade PCa (p = 0.002) and EAU biochemical recurrence risk (p = 0.044), but not extracapsular extension (p = 0.072), seminal vesicle invasion (p = 0.482) and T stage (p = 0.457). Regression analysis showed that the AUC increased from 0.806 (base model) to 0.873 (PCA3 model). PCA3 model with cutoff 0.15 could reduce 35.3% prostate biopsies and delay 5.8% high-grade PCa., Conclusions: PCA3 had a better diagnosis accuracy than tPSA, %fPSA and PSAD. PCA3 was a significantly independent predictor for risk stratification, suggesting that PCA3 could provide incremental value to reduce unnecessary prostate biopsies., Competing Interests: Declarations. Ethics approval and consent to participate: Approval was obtained from the respective ethics committee (The First Affiliated Hospital, Zhejiang University School of Medicine; the Second Affiliated Hospital, Zhejiang University School of Medicine; Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University; West China Hospital, Sichuan University). The procedures used in this study adhere to the tenets of the Declaration of Helsinki. The consents were given voluntarily by study participants and the approvals were obtained from all participants. Consent for publication: Informed consent was obtained from all individuals participating in the study. Competing interests: C.J is an employee of York Biotech Co., Ltd, which is developing products related to the research presented here. The other authors declare no competing interests., (© 2024. The Author(s).)

Background: The inverse relationship between serum Klotho levels and systemic inflammation, particularly C-reactive protein (CRP), has been suggested in limited studies. However, the association within a large and diverse population remains underexplored., Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) to investigate the association between serum Klotho levels and CRP among a nationally representative sample of the US population. Multiple linear regression analyses were performed to assess this relationship while adjusting for relevant covariates. Stratified analysis with interaction, restricted cubic splines (RCS) were employed to support the research objectives., Results: A total of 5901 participants had a mean age of 57.9 ± 11.0 years, with 49.4% of them being male and 50.6% of them being female. A negative association between serum Klotho and CRP was revealed in the fully adjusted model (β -0.26; 95% CI -0.41∼-0.11). When serum Klotho was taken as quartiles with Q1 as reference, the adjusted β that were lowest in Q4 were - 0.1 (95% CI -0.16∼-0.04, p-value = 0.002) in model 4, respectively. These statistics were robust in stratified analyses., Conclusion: While our study demonstrates an inverse association between serum Klotho levels and CRP, suggesting a potential cardioprotective role of Klotho, it is important to note that our cross-sectional design does not permit the establishment of causality. Therefore, we cannot definitively conclude that increasing Klotho levels will directly reduce cardiovascular risk. Our findings do, however, highlight the need for further research to explore the potential of Klotho as a therapeutic target for cardiovascular health., Competing Interests: Declarations. Ethics approval and consent to participate: The NCHS Research Ethics Review Board approved the NHANES study protocol, and participants provided written informed consent at enrollment (the website is https://www.cdc.gov/nchs/nhanes/irba98.htm ). Ethical approval and consent were not required as this study was based on publicly available de-identified data. Consent for publication: not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Increasing evidence suggests that mesenchymal stem cells (MSCs) repair traumatized tissues primarily through paracrine secretion and differentiation into specific cell types. However, the role of epithelial differentiation of MSCs in cutaneous wound healing is unclear. This study aimed to investigate the epithelial differentiation potential of gingival tissue-derived MSCs (GMSCs) in epithelial cell growth medium and the mechanisms underlying their differentiation into an epithelial-like cell phenotype., Methods: We used scanning electron microscopy to examine GMSCs for epithelial differentiation. Quantitative real-time polymerase chain reaction and Western blotting were respectively used to measure genes and proteins related to epithelial differentiation. Immunofluorescence was used to examine subcellular localization of KLF4, KRT19, and β-catenin proteins. Transcriptome sequencing was used to enrich the mechanisms underlying epithelial differentiation in GMSCs. An MSAB inhibitor was used to validate the Wnt signaling pathway further. The wound healing rate and re-epithelialization were assessed through macroscopical observation and hematoxylin and eosin staining., Results: GMSCs cultured in epithelial cell growth medium from days 3 to 15 exhibited decreased expression of mesenchymal-epithelial transition and stemness-related proteins (N-cadherin, Vimentin, KLF4, and SOX2), increased expression of epithelial-related proteins (KRT12, KRT15, KRT19, and E-cadherin), and exhibited epithelial-like morphology. Mechanistically, high-throughput sequencing revealed that the Wnt and TGF-beta signaling pathways were inhibited during epithelial differentiation of GMSCs (Epi-GMSCs). MSAB-induced Wnt signaling pathway inhibition promoted epithelial-related gene and protein expression. Furthermore, we demonstrated the ability of Epi-GMSCs to facilitate wound healing by improving re-epithelialization in a full-thickness skin defect model., Conclusions: Collectively, this study uncovers that GMSCs have the ability to differentiate into epithelia and highlights a promising strategy for using Epi-GMSCs to improve cutaneous wound healing., Competing Interests: Declarations. Ethics approval and consent to participate: The original sources (Bluef Biotechnology Development Co., Ltd. and Dr. Zhentian Xu’s lab) have confirmed that there was initial ethical approval for collection of human cells, and that the donors had signed informed consent. The animal study protocol was approved by the Ethics Committee of Zhejiang University (Title of the approved project: Epithelial differentiation of gingival mesenchymal stem cells enhances re-epithelialization for full-thickness cutaneous wound healing; Approval No: ZJU20230339; Date of approval: 2023.09.06) and conducted in accordance with the ARRIVE (Animal Research: Reporting of In vivo Experiments) guidelines 2.0. Consent for publication: All authors agreed to the publication of this paper. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) ranks among the most lethal malignancies around the world. However, the current management strategies for predicting prognosis in HCC patients remain unreliable. Our study developed a robust prognostic model based on glutamine metabolism associated-genes (GMAGs), utilizing data from The Cancer Genome Atlas database. The prognostic values of model were validated through the databases of the Gene Expression Omnibus and International Cancer Genome Consortium via Kaplan‒Meier curves and receiver operating characteristic (ROC). The potential biological pathways associated with prognostic risk were investigated through different enrichment analysis, and Gene variation analysis. The correlation between prognostic model and therapeutic responses were analyzed. Quantitative real-time PCR (qRT-PCR) and cellular experiments were measured to analyze the GMAGs. Consequently, a prognostic model was constructed of 4 GMAGs (RRM1, RRM2, G6PD, and GPX7) through least absolute shrinkage and selection operator (LASSO) regression analysis. The Kaplan‒Meier curves and ROC curves showed a reliable predictive capacity of prognosis for HCC patients (p < 0.05). The enrichment analyses revealed a multitude of biological pathways that are significantly associated with cancer. Patients with high prognostic risk might be sensitive to immunotherapy (p < 0.05). The results of qRT-PCR revealed that all 4 GMAGs exhibited significantly higher expression levels in HCC samples compared to normal samples (p < 0.05). Moreover, the knockdown of RRM1 suppresses the progression of HCC cells. In this study, we developed a robust prognostic model for predicting the prognosis of HCC patients based on GMAGs, and identified RRM1 as a potential therapeutic target for HCC., Competing Interests: Declarations Ethical approval This research was approved by the Ethics Committee of Dalian medical university. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: To ensure workforce stability in China's healthcare system and maintain high-quality care, it is essential to comprehensively understand the interplay of factors contributing to turnover intention of healthcare workers. This study aims to examine the associations between potential factors and turnover intention in healthcare workers and explore the mediating effect of job satisfaction and work engagement in the association between them., Methods: In this cross-sectional study, a random sample of 1060 healthcare workers working in 98 public medical institutions were recruited to rate their turnover intention in 2018 in Shenzhen, China. Information on socio-demographic characteristics, job-related factors, turnover intention, job satisfaction, work engagement, work stress and doctor-patient relationship of participants were collected. Pearson's chi-squared tests and binary logistic regression analyses were performed to explore the association between these factor and turnover intention. Mediation analysis was used to explore the roles of potential mediators and moderators., Results: The results showed that age (OR: 0.35, 95%CI: 0.16 to 0.72), tenure (OR: 0.98, 95%CI: 0.96 to 0.99), administrative positions (OR: 0.33, 95%CI: 0.16 to 0.63), and night shift frequency (OR: 1.84, 95%CI: 1.26 to 2.67) were significantly associated with turnover intention. We identified the mediating effect of job satisfaction and work engagement in the relationship between administrative positions and turnover intention, while the suppressing effect in the relationship between professional titles and turnover intention. Additionally, we found that monthly income plays a moderating role in the relationship between work engagement and turnover intention, and in the association between professional titles and turnover intention., Conclusions: Greater job satisfaction and engagement, along with reasonable remuneration, were found to be associated with lower turnover intention among healthcare workers. Employers should proactively monitor the dynamic interactions among these factors and then develop more tailored interventions in order to alleviate the ongoing loss of healthcare workers., Competing Interests: Declarations Ethics approval and consent to participate The Sixth NHSS obtained ethics approval from the institutional review board of the Chinese National Bureau of Statistics (license number 2018-87) and was conducted in accordance with the Declaration of Helsinki. All participants gave informed consent to participate in the study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

With the emergence of the new generation vision architecture Vmamba and the further demand for agricultural yield and efficiency, we propose an efficient and high-accuracy target detection network for automated pear picking tasks based on Vmamba, aiming to address the issue of low efficiency in current Transformer architectures. The proposed network, named SRSMamba, employs a Reward and Punishment Mechanism (RPM) to focus on important information while minimizing redundancy interference. It utilizes 3D Selective Scan (SS3D) to extend scanning dimensions and integrates global information across channel dimensions, thereby enhancing the model's robustness in complex agricultural environments and effectively adapting to the extraction of complex features in pear orchards and farmlands. Additionally, a Stacked Feature Pyramid Network (SFPN) is introduced to enhance semantic information during the feature fusion stage, particularly improving the detection capability for small targets. Experimental results show that SRSMamba has a low parameter count of 21.1 M, GFLOPs of 50.4, mAP of 72.0%, mAP50 reaching 94.8%, mAP75 at 68.1%, and FPS at 26.9. Compared with other state-of-the-art (SOTA) object detection methods, it achieves a good trade-off between model efficiency and detection accuracy., (© 2024. The Author(s).)

In recent decades, cancer has posed a challenging obstacle that humans strive to overcome. While phototherapy and immunotherapy are two emerging therapies compared to traditional methods, they each have their advantages and limitations. These limitations include easy metastasis and recurrence, low response rates, and strong side effects. To address these issues, researchers have increasingly focused on combining these two therapies by utilizing a nano-drug delivery system due to its superior targeting effect and high drug loading rate, yielding remarkable results. The combination therapy demonstrates enhanced response efficiency and effectiveness, leading to a preparation that is highly targeted, responsive, and with low recurrence rates. This paper reviews several main mechanisms of anti-tumor effects observed in combination therapy based on the nano-drug delivery system over the last five years. Furthermore, the challenges and future prospects of this combination therapy are also discussed., (© 2024. The Author(s).)

The pandemic crisis outbreak has impacted the hospitality industry tremendously. This study investigated the effect of job insecurity on service performance and examined the mediating role of cognitive appraisal and the moderating effect of uncertainty tolerance from the perspectives of cognitive appraisal theory of stress. The study collected a questionnaire from 316 hotel employees at three time points, with a one-month interval between the two time points. The SPSS PROCESS macro and MPLUS are used to test the research hypotheses. The results highlighted that the mediating role of challenge-hindrance appraisal, affirming that job insecurity positively impacts service performance via increasing challenge appraisal, and job insecurity negatively impacts service performance via increasing hindrance appraisal. Furthermore, the results show that uncertainty tolerance moderates the relationship between job insecurity and cognitive appraisal and also moderated the indirect effect of job insecurity on service performance through cognitive appraisal. The research results provide implications for human resource management in the hospitality industry., (© 2024. The Author(s).)

Background: Urinary incontinence is frequent in the general population and affects men and women of all ages. UI carries an unsuspected load on the healthcare system. To investigate whether urinary incontinence is associated with all-cause, cardiovascular disease (CVD) and cancer mortality among US adults., Methods: The analyzed data was collected from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) data. A total of 25,182 US participants with complete information about follow-up information and urinary incontinence (UI) were included in this cohort study. Univariate Cox regression analyses, the UpSet plot, multivariate Cox regression analysis, subgroup analysis of all-cause mortality, and Kaplan-Meier survival curve were employed to support the research objectives., Results: A total of 25,182 participants had a mean age of 49.8 ± 17.8 years, with 49.3% of them being male and 50.7% of them being female. In the unadjusted model, we found that the risk of all-cause mortality increased by 12% (95% CI 1.03-1.22, P = 0.008), the risk of CVD mortality increased by 21% (95% CI 1.07-1.36, P = 0.002), and the risk of Cancer mortality increased by 8% (95% CI 0.95-1.22, P = 0.243) among individuals with urinary incontinence. After adjusting for multiple variables, we found that the risk of all-cause mortality in patients with urinary incontinence decreased by 1% (95% CI 0.9-1.09), but this decrease was statistically insignificant (P = 0.868), and the risk of Cancer mortality decreased by 3% (95% CI 0.84-1.12, P = 0.686). The association between urinary incontinence and mortality risk were stable in stratified analyses., Conclusions: In our study, we found that urinary incontinence itself is an independent risk factor for death. The association between urinary incontinence and mortality became less significant after adjusting for covariates, this is a common occurrence in statistical analysis. Future research, with larger sample sizes and more robust study designs, is needed to further elucidate the complex relationship between urinary incontinence and mortality risk., (© 2024. The Author(s).)

Background: To assess the efficacy and safety of virtual reality-based visual training (VRVT) in myopia control among children., Methods: The randomized, parallel-group, single-blind clinical trial conducted at the Department of Ophthalmology of Shanghai Tenth People's Hospital enrolled 65 low-myopic children (aged 8 to 13 years) with cycloplegic spherical equivalent (SE) between - 0.50 and - 3.00 diopters (D), astigmatism less than - 1.00 D, anisometropia less than 1.50D, and best corrected visual acuity (BCVA) more than 0.0 logarithm (LogMAR) of the minimum angle of resolution. The participants were enrolled in December 2020, and the follow-up of this study concluded on August 2021. Children were assigned randomly to the intervention group (VRVT plus single-vision spectacle [SVS]) and the control group (only SVS without receiving VRVT). The intervention group was administered for 20 min per day with VRVT under parental supervision at home. The primary outcome was changes in axial length (AL) at 3 months. Macular choroidal thickness (mCT) was regarded as a key secondary outcome., Results: Among 65 participants (mean age: 10.8 years, 52.3% male), 60 children (92.3%) who completed the 3-month intervention and 6-month follow-up were included in the analysis (30 in the intervention group and 30 in the control group). The changes of AL were 0.063 ± 0.060 mm (95% confidence interval [CI], 0.074 to 0.119 mm) in the intervention group and 0.129 ± 0.060 mm (95% CI, 0.107 to 0.152 mm) and in the control group at 3 months (t = - 2.135, P = 0.037), and the mean difference between the two groups was 0.066 mm. The change of mCT were 22.633 ± 36.171 μm (95% CI, 9.127 to 36.140 μm) in the intervention group and - 3.000 ± 31.056 μm (95% CI, - 14.597 to 8.597 μm) in the control group at 3 months (t = 2.945, P = 0.005). VR vertigo was the most common adverse event which was occurred in two children (2/30, 6.67%) in the intervention group., Conclusions: VRVT is a promising method for myopia control in children with good user acceptability. Among children aged 8 to 13 years with low-myopia, nightly use of VRVT resulted in slowing myopia progression., Trial Registration: This protocol was registered with ClinicalTrials.gov (NCT06250920), retrospectively registered on 01 February 2024., (© 2024. The Author(s).)

Objective: Obesity is a common feature in women with polycystic ovary syndrome (PCOS) and potentially significantly influences reproductive function. However, opinions are divided as to which factor is a more appropriate obesity predictor of reproductive outcomes. The aim of this study was to investigate the discriminatory capability of anthropometric measures in predicting reproductive outcomes in Chinese women with PCOS., Methods: A total of 998 women with PCOS from PCOSAct were included. Logistic regression models were used to compute the odds ratios (ORs) and 95% confidence interval (95% CIs) to assess the effect of anthropometric measures, including body mass index (BMI), waist circumference (WC), hip circumference (HC), the waist‒hip ratio (WHR) and the waist‒height ratio (WHtR), on reproductive outcomes. The discrimination abilities of the models were assessed and compared based on the area under the receiver operating characteristic curve (AUC), Akaike's information criterion (AIC) and integrated discrimination improvement (IDI)., Results: Among PCOS women, there was a graded association between anthropometric measures and predicted reproductive outcomes across quintiles of anthropometric measures, including a linear association among WHR, BMI and reproductive outcomes and among waist circumference, WHtR and live birth, pregnancy, and ovulation. However, only a linear association was noted between the hip and ovulation. C-statistic comparisons and IDI analyses revealed a trend towards a significant superiority of BMI for ovulation and WHR for live birth, pregnancy and conception in the models. Combining obesity variables improved discrimination in the multivariable models for reproductive outcomes., Conclusions: Our findings support that BMI is a better predictor of ovulation and that the WHR is a better predictor of live birth, pregnancy and conception, whereas the combination of obesity variables contributes to the discrimination of reproduction., (© 2024. The Author(s).)

Background: Hypoxia plays an important role in the chemotherapy resistance of nasopharyngeal carcinoma (NPC). Ferroptosis is a newly discovered form of programmed cell death and ferroptosis inducers showed promising therapeutic effects in some cancers. However, the sensibility of NPC cells to ferroptosis under the hypoxic microenvironment is still unclear, and this study was designed to clarify it., Methods: NPC cells, treated with erastin, were placed in a normoxia or hypoxic environment (5% CO 2 , 94% N 2 and 1% O 2 ) at 37℃for 24 h. After exposed to hypoxia, ferroptosis-associated phenotypes were detected by CCK8, MDA, GSH, lipid ROS and Fe. The gene expression profiles of head and neck squamous cell carcinoma (HNSCC) tissues were downloaded from the TCGA database to screen construction molecule. BAP1 was screened out and its functions on erastin-induced ferroptosis in NPC cells were detected by knockdown of BAP1. Luciferase reporter assay and co-IP experiment were performed to explore the molecular mechanism. Finally, the tumour xenograft model was applied to further verify these results in vivo., Results: CCK8 assay showed that IC 50 of NPC cells treated with erastin under hypoxia was significantly lower than that under normoxia. Hypoxia significantly increased the levels of lipid ROS and MDA, and decreased GSH content induced by erastin. A prognostic risk model for HNSCC with six ferroptosis-related genes was constructed and validated based on TCGA database. BAP1 was significantly up-regulated under hypoxia, and luciferase reporter assay showed that HIF-1α was an upstream transcription regulator of BAP1. Knockdown of BAP1 in NPC cells significantly increased the IC 50 value of erastin under hypoxia and significantly ameliorated erastin-induced ferroptosis under hypoxia in aspect of lipid ROS, MDA content and GSH. Co-IP results showed that BAP1 mediated deubiquitination of H2A and decreased SLC7A11 expression. Finally, knockdown of BAP1 reduced sensitivity to erastin-induced ferroptosis in a tumour xenograft model. And the level of H2A was significantly decreased in xenograft tumors of BAP1 knockdown cells., Conclusion: Hypoxia-induced BAP1 enhances erastin-induced ferroptosis in NPC by stabilizing H2A. Ferroptosis inducers targeting BAP1 may be an effective way to improve chemotherapy resistance in NPC, especially in the hypoxic microenvironment., (© 2024. The Author(s).)

Objective: Data imbalance is a pervasive issue in medical data mining, often leading to biased and unreliable predictive models. This study aims to address the urgent need for effective strategies to mitigate the impact of data imbalance on classification models. We focus on quantifying the effects of different imbalance degrees and sample sizes on model performance, identifying optimal cut-off values, and evaluating the efficacy of various methods to enhance model accuracy in highly imbalanced and small sample size scenarios., Methods: We collected medical records of patients receiving assisted reproductive treatment in a reproductive medicine center. Random forest was used to screen the key variables for the prediction target. Various datasets with different imbalance degrees and sample sizes were constructed to compare the classification performance of logistic regression models. Metrics such as AUC, G-mean, F1-Score, Accuracy, Recall, and Precision were used for evaluation. Four imbalance treatment methods (SMOTE, ADASYN, OSS, and CNN) were applied to datasets with low positive rates and small sample sizes to assess their effectiveness., Results: The logistic model's performance was low when the positive rate was below 10% but stabilized beyond this threshold. Similarly, sample sizes below 1200 yielded poor results, with improvement seen above this threshold. For robustness, the optimal cut-offs for positive rate and sample size were identified as 15% and 1500, respectively. SMOTE and ADASYN oversampling significantly improved classification performance in datasets with low positive rates and small sample sizes., Conclusions: The study identifies a positive rate of 15% and a sample size of 1500 as optimal cut-offs for stable logistic model performance. For datasets with low positive rates and small sample sizes, SMOTE and ADASYN are recommended to improve balance and model accuracy., (© 2024. The Author(s).)

Purpose: Inflammatory factors play an important role in the onset and progression of colorectal cancer (CRC). This study aimed to develop and validate a novel scoring system that utilizes specific inflammatory factor indicators to predict intestinal obstruction in CRC patients., Methods: This study conducted a retrospective analysis of 1,470 CRC patients who underwent surgical resection between January 2013 and July 2018. These patients were randomly allocated to the training group (n = 1060) and the validation group (n = 410). Univariate and multivariate logistic regression analyses were performed to identify independent predictive factors for intestinal obstruction. The CRC peculiar inflammation score (CPIS), comprising lymphocyte-to-monocyte ratio (LMR), prognostic nutrition index (PNI), and alanine transaminase-to-lymphocyte ratio index (ALRI) scores, was significantly associated with the occurrence of intestinal obstruction. A nomogram combining CPIS with other clinical features was developed to predict this occurrence. Model accuracy was assessed by determining the area under the receiver operating characteristic (ROC) curve (AUC)., Results: The CPIS generated by multi-factor logistic regression was as follows: - 1.576 × LMR - 0.067 × PNI + 0.018 × ALRI. Using CPIS cutoff values of 50% (- 7.188) and 85% (- 6.144), three predictive groups were established. Patients with a high CPIS had a significantly higher risk of intestinal obstruction than those with a low CPIS (odds ratio [OR]: 10.0, confidence interval [CI]: 5.85-17.08, P < 0.001). The predictive nomogram demonstrated good calibration and discrimination abilities. The AUC of the ROC curve for the obstruction nomogram was 0.813 (95% CI: 0.777-0.850) in the training set and 0.806 (95% CI: 0.752-0.860) in the validation set. The calibration curve exhibited neither bias nor high credibility. Decision curve analysis indicated the utility of this predictive model., Conclusion: CRC-associated intestinal obstruction is closely linked to inflammatory markers in patients. CPIS is a CRC-specific inflammatory predictive score based on a combination of inflammatory-related indicators. A high CPIS serves as a strong indicator of intestinal obstruction. Its integration with other clinical factors and preoperative inflammatory-specific indicators significantly enhances the diagnosis and treatment of CRC patients with intestinal obstruction., (© 2024. The Author(s).)

Background: To develop and validate a nomogram model based on Gd-EOB-DTPA enhanced MRI for differentiation between hepatocellular carcinoma (HCC) and focal nodular hyperplasia (FNH) showing iso- or hyperintensity in the hepatobiliary phase (HBP)., Methods: A total of 75 patients with 49 HCCs and 26 FNHs randomly divided into a training cohort (n = 52: 34 HCC; 18 FNH) and an internal validation cohort (n = 23: 15 HCC; 8 FNH). A total of 37 patients (n = 37: 25 HCC; 12 FNH) acted as an external test cohort. The clinical and imaging characteristics between HCC and FNH groups in the training cohort were compared. The statistically significant parameters were included into the FAE software, and a multivariate logistic regression classifier was used to identify independent predictors and establish a nomogram model. Receiver operating characteristic (ROC) curves were used to evaluate the prediction ability of the model, while the calibration and decision curves were used for model validation. Subanalysis was used to compare qualitative and quantitative characteristics of patients with chronic hepatitis and cirrhosis between the HCC and FNH groups., Results: In the training cohort, gender, age, enhancement rate in the arterial phase (AP), focal defects in uptake were significant predictors for HCC showing iso- or hyperintensity in the HBP. In the training cohort, area under the curve (AUC), sensitivity and specificity of the nomogram model were 0.989(95%CI: 0.967-1.000), 97.1% and 94.4%. In the internal validation cohort, the above three indicators were 0.917(95%CI: 0.782-1.000), 93.3% and 87.5%. In the external test cohort, the above three indicators were 0.960(95%CI: 0.905-1.000), 84.0% and 100.0%. The results of subanalysis showed that age was the independent predictor in the patients with chronic hepatitis and cirrhosis between HCC and FNH groups., Conclusions: Gd-EOB-DTPA enhanced MRI nomogram model may be useful for discriminating HCC and FNH showing iso- or hyperintensity in the HBP before surgery., (© 2024. The Author(s).)

Background: Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5-10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage., Methods: The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group., Results: There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group., Conclusion: This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies., (© 2024. The Author(s).)

Background: Postoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present., Methods: The objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2-3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events., Discussion: This clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population., Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ChiCTR2300074803. Registered on August 16, 2023., (© 2024. The Author(s).)

Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors β-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/β-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing., (© 2024. The Author(s).)

Background: Microtubule polymerization is usually considered as the upstream of apoptotic cell death induced by taxanes, but recently published studies provide more insights into the mechanisms responsible for the antineoplastic effect of taxanes. In this study, we figure out the role of the stress-related PERK/eIF2α axis in tumor cell death upon taxane treatment along with paclitaxel resistance., Methods: Utilizing immunoblot assay, the activation status of PERK-eIF2α signaling was detected in a panel of cancer cell lines after the treatment of taxanes. The causal role of PERK-eIF2α signaling in the cancer cell apoptosis induced by taxanes was examined via pharmacological and genetic inhibitions of PERK. The relationship between microtubule polymerization and PERK-eIF2α activation was explored by immunofluorescent and immunoblotting assays. Eventaually, the combined therapeutic effect of paclitaxel (PTX) and CCT020312, a PERK agonist, was investigated in PTX-resistant breast cancer cells in vitro and in vivo., Results: PERK-eIF2α axis was dramatically activated by taxanes in several cancer cell types. Pharmacological or genetic inhibition of PERK efficiently impaired taxane-induced apoptotic cell death, independent of the cellular microtubule polymerization status. Moreover, PTX was able to activate the PERK/eIF2α axis in a very low concentration without triggering microtubule polymerization. In PTX-resistant breast cancer cells, the PERK/eIF2α axis was attenuated in comparison with the PTX-sensitive counterparts. Reactivation of the PERK/eIF2α axis in the PTX-resistant breast cancer cells with PERK agonist sensitized them to PTX in vitro. Combination treatment of the xenografted PTX-resistant breast tumors with PERK agonist and PTX validated the synergic effect of PTX and PERK activation in vivo., Conclusion: Activation of the PERK/eIF2α axis is a pivotal prerequisite of taxanes to initiate cancer cell apoptosis, which is independent of the well-known microtubule polymerization-dependent manner. Simultaneous activation of PERK-eIF2α signaling would be a promising therapeutic strategy to overcome PTX resistance in breast cancer or other cancers., (© 2024. The Author(s).)

Background: The risk of arrhythmia is usually assessed by the length of the corrected QT interval (QTc) when patients use antipsychotics. Prolonged QTc intervals are thought to increase the probability of malignant ventricular arrhythmias, and if we focus only on the QTc interval, we may be influenced by a single factor and make decisions that are not conducive to effective treatment. The index of cardiac electrophysiological balance (iCEB) is considered more valuable than the QTc for predicting drug-induced arrhythmias. It has been used in clinical practice, but no studies have observed changes in this index after the use of antipsychotics., Objective: To investigate the changes in ventricular repolarization indices and the occurrence of arrhythmias in patients who have been using antipsychotic drugs for a long time, to compare the changes in iCEBc and QTc and to predict abnormal iCEBc values., Methods: Patients with schizophrenia who had been hospitalized for more than 4 years and who were receiving atypical antipsychotics underwent a 12-lead synchronized electrocardiogram (ECG) every 2-4 weeks. The baseline data were measured at admission, defined as the baseline (time0), and the most obvious abnormal changes in ventricular depolarization and repolarization measured every 12 months were one-year follow-up (time1), two-year follow-up (time2), three-year follow-up (time3), and four-year follow-up (time4). Repeated measures analysis of variance was used for comparisons. The types and doses of drugs taken at 5 time points were recorded and converted into chlorpromazine equivalents for comparison. The incidence of arrhythmia during the observation cycle was recorded., Results: The patients had been treated with antipsychotic medication for 4 years, and the duration of the QRS wave was longer in males than in females. TpTe, TpTe/QRS, TpTe/QT, TpTe/QTc, iCEB, and iCEBc increased significantly with hospital stay, while TpTe, TpTe/QRS, TpTe/QT, and TpTe/QTc exhibited more obvious changes in these indicators in female patients (P < 0.01). The changes in iCEB and iCEBc were more significant in males (P < 0.01). The incidences of arrhythmia (arrhythmic events included premature ventricular beats and premature atrial beats) within 5 time points were 2.5%, 6.25%, 6.25%, 6.25% and 5%, respectively. More than 90% of patients treated with antipsychotics did not have any arrhythmias. No TdP syncope or other cardiovascular symptoms were found in any of the patients., Conclusion: After long-term use of antipsychotics, the ventricular repolarization index gradually increased with time. The new ventricular repolarization indices iCEB and iCEBc were more sensitive than the QTc at predicting arrhythmia. According to the abnormal QTc values in men and women, we predict that the abnormal value of the iCEBc in males is 4.528 and that in females is 5.315., (© 2024. The Author(s).)

DNA nanostructures have long been developed for biomedical purposes, but their controlled delivery in vivo proposes a major challenge for disease theranostics. We previously reported that DNA nanostructures on the scales of tens and hundreds nanometers showed preferential renal excretion or kidney retention, allowing for sensitive evaluation and effective protection of kidney function, in response to events such as unilateral ureter obstruction or acute kidney injury. Encouraged by the positive results, we redirected our focus to the liver, specifically targeting organs noticeably lacking DNA materials, to explore the interaction between DNA nanostructures and the liver. Through PET imaging, we identified SDF and M13 as DNA nanostructures exhibiting significant accumulation in the liver among numerous candidates. Initially, we investigated and assessed their biodistribution, toxicity, and immunogenicity in healthy mice, establishing the structure-function relationship of DNA nanostructures in the normal murine. Subsequently, we employed a mouse model of liver ischemia-reperfusion injury (IRI) to validate the nano-bio interactions of SDF and M13 under more challenging pathological conditions. M13 not only exacerbated hepatic oxidative injury but also elevated local apoptosis levels. In contrast, SDF demonstrated remarkable ability to scavenge oxidative responses in the liver, thereby mitigating hepatocyte injury. These compelling results underscore the potential of SDF as a promising therapeutic agent for liver-related conditions. This aimed to elucidate their roles and mechanisms in liver injury, providing a new perspective for the biomedical applications of DNA nanostructures., (© 2024. The Author(s).)

Objective: Osteoporosis (OS) is a systemic bone disease characterized by low bone mass and bone microstructure damage. This study., Methods: According to the T value, 88 elderly fracture patients were grouped as the control group (without OS, 43 cases) and observation group (with T value <-2.5, which could be diagnosed as OS, 45 cases). The content of boney containing protein (BGP), total type 1 collagen amino terminal extender peptide (TPINP), β-Crosslaps (β-CTX), parathyroid hormone (PTH) and insulin-like growth factors-1 (IGF-1) was compared. Multivariate logistic regression was adopted to analyze the correlation between biochemical indexes and the occurrence of senile OS fracture and the related risk factors. The diagnostic value in the elderly was analyzed by receiver operating characteristic (ROC) curve., Results: The levels of BGP, TPINP, β-CTX, PTH and IGF-1 were elevated, and the level of IGF-1 was decreased in the observation group compared with the control group (P < 0.05). The elevated content of BGP, TPINP, β-CTX and PTH, and the decreased expression of IGF-1 were influencing factors for OS fractures in the elderly (P < 0.05). The sensitivity and specificity to predict the occurrence of OS fractures in the elderly were 91.70% and 90.50%, respectively. The AUC of combined detection was 0.976 (95% CI: 0.952-1.000), which was memorably higher than single indicator detection (P < 0.05). Among 45 patients, 32 cases had good prognosis and 13 had poor prognosis. In comparison with the good prognosis group, the content of BGP, TPINP, β-CTX and PTH were sensibly higher, the level of IGF-1 was prominently lower, and the proportion of fracture history was much higher in poor prognosis group (P < 0.05). Fracture history, BGP, TPINP, β-CTX, PTH and IGF-1 were independent risk factors for poor prognosis of elderly OS fractures (P < 0.05)., Conclusion: Bone metabolism factors were associated with poor prognosis of OS in the elderly. The combined detection had higher diagnostic value in calculating the risk of OS fracture in the elderly than single indicator detection., (© 2024. The Author(s).)

L-type calcium channels (LTCCs), the largest subfamily of voltage-gated calcium channels (VGCCs), are the main channels for Ca 2+ influx during extracellular excitation. LTCCs are widely present in excitable cells, especially cardiac and cardiovascular smooth muscle cells, and participate in various Ca 2+ -dependent processes. LTCCs have been considered as worthy drug target for cardiovascular, neurological and psychological diseases for decades. Natural products from Traditional Chinese medicine (TCM) have shown the potential as new drugs for the treatment of LTCCs related diseases. In this review, the basic structure, function of LTCCs, and the related human diseases caused by structural or functional abnormalities of LTCCs, and the natural LTCCs antagonist and their potential usages were summarized., (© 2024. The Author(s).)

Background: Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored., Results: Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells., Conclusions: In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets., (© 2024. The Author(s).)

Background: Expression quantitative trait loci (eQTL) studies aim to understand the influence of genetic variants on gene expression. The colocalization of eQTL mapping and GWAS strategy could help identify essential candidate genes and causal DNA variants vital to complex traits in human and many farm animals. However, eQTL mapping has not been conducted in ducks. It is desirable to know whether eQTLs within GWAS signals contributed to duck economic traits., Results: In this study, we conducted an eQTL analysis using publicly available RNA sequencing data from 820 samples, focusing on liver, muscle, blood, adipose, ovary, spleen, and lung tissues. We identified 113,374 cis-eQTLs for 12,266 genes, a substantial fraction 39.1% of which were discovered in at least two tissues. The cis-eQTLs of blood were less conserved across tissues, while cis-eQTLs from any tissue exhibit a strong sharing pattern to liver tissue. Colocalization between cis-eQTLs and genome-wide association studies (GWAS) of 50 traits uncovered new associations between gene expression and potential loci influencing growth and carcass traits. SRSF4, GSS, and IGF2BP1 in liver, NDUFC2 in muscle, ELF3 in adipose, and RUNDC1 in blood could serve as the candidate genes for duck growth and carcass traits., Conclusions: Our findings highlight substantial differences in genetic regulation of gene expression across duck primary tissues, shedding light on potential mechanisms through which candidate genes may impact growth and carcass traits. Furthermore, this availability of eQTL data offers a valuable resource for deciphering further genetic association signals that may arise from ongoing extensive endeavors aimed at enhancing duck production traits., (© 2024. The Author(s).)

Background: Obesity affects approximately 800 million people worldwide and may contribute to various diseases, especially cardiovascular and cerebrovascular conditions. Fat distribution and content represent two related yet distinct axes determining the impact of adipose tissue on health. Unlike traditional fat measurement indices, which often overlook fat distribution, the Chinese visceral adiposity index (CVAI) is a novel metric used to assess visceral fat accumulation and associated health risks. Our objective is to evaluate its association with the risk of cardiovascular and cerebrovascular diseases., Methods: A nationwide longitudinal study spanning 9 years was conducted to investigate both the effects of baseline CVAI levels (classified as low and high) and dynamic changes in CVAI over time, including maintenance of low CVAI, transition from low to high, transition from high to low, and maintenance of high CVAI. Continuous scales (restricted cubic spline curves) and categorical scales (Kaplan-Meier curves and multivariable Cox regression analyses) were utilized to evaluate the relationship between CVAI and cardiovascular and cerebrovascular diseases. Furthermore, subgroup analyses were conducted to investigate potential variations., Results: Totally 1761 individuals (22.82%) experienced primary outcomes among 7717 participants. In the fully adjusted model, for each standard deviation increase in CVAI, there was a significant increase in the risk of primary outcomes [1.20 (95%CI: 1.14-1.27)], particularly pronounced in the high CVAI group [1.38 (95%CI: 1.25-1.54)] compared to low CVAI group. Regarding transition patterns, individuals who consistently maintained high CVAI demonstrated the highest risk ratio compared to those who consistently maintained low CVAI [1.51 (95%CI: 1.31-1.74)], followed by individuals transitioning from low to high CVAI [1.22 (95% CI: 1.01-1.47)]. Analysis of restricted cubic spline curves indicated a positive dose-response relationship between CVAI and risk of primary outcomes (p for non-linear = 0.596). Subgroup analyses results suggest that middle-aged individuals with high CVAI face a notably greater risk of cardiovascular and cerebrovascular diseases in contrast to elderly individuals [1.75 (95% CI: 1.53-1.99)]., Conclusion: This study validates a significant association between baseline levels of CVAI and its dynamic changes with the risk of cardiovascular and cerebrovascular diseases. Vigilant monitoring and effective management of CVAI significantly contribute to early prevention and risk stratification of cardiovascular and cerebrovascular diseases., (© 2024. The Author(s).)

Background: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants., Case Presentation: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved., Conclusions: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established., (© 2024. The Author(s).)

Background: Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death., Methods: We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose., Results: MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis., Conclusion: The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC., (© 2024. The Author(s).)

Background: Cystic fibrosis is a chronic genetic disease that can affect the function of the respiratory system. Previous reviews of the effects of respiratory muscle training in people with cystic fibrosis are uncertain and do not consider the effect of age on disease progression. This systematic review aims to determine the effectiveness of respiratory muscle training in the clinical outcomes of children and adolescents with cystic fibrosis., Methods: Up to July 2023, electronic databases and clinical trial registries were searched. Controlled clinical trials comparing respiratory muscle training with sham intervention or no intervention in children and adolescents with cystic fibrosis. The primary outcomes were respiratory muscle strength, respiratory muscle endurance, lung function, and cough. Secondary outcomes included exercise capacity, quality of life and adverse events. Two review authors independently extracted data and assessed study quality using the Cochrane Risk of Bias Tool 2. The certainty of the evidence was assessed according to the GRADE approach. Meta-analyses where possible; otherwise, take a qualitative approach., Results: Six studies with a total of 151 participants met the inclusion criteria for this review. Two of the six included studies were published in abstract form only, limiting the available information. Four studies were parallel studies and two were cross-over designs. There were significant differences in the methods and quality of the methodology included in the studies. The pooled data showed no difference in respiratory muscle strength, lung function, and exercise capacity between the treatment and control groups. However, subgroup analyses suggest that inspiratory muscle training is beneficial in increasing maximal inspiratory pressure, and qualitative analyses suggest that respiratory muscle training may benefit respiratory muscle endurance without any adverse effects., Conclusions: This systematic review and meta-analysis indicate that although the level of evidence indicating the benefits of respiratory muscle training is low, its clinical significance suggests that we further study the methodological quality to determine the effectiveness of training., Trial Registration: The protocol for this review was recorded in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023441829., (© 2024. The Author(s).)

Background: Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis., Methods: LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently., Results: The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment., Conclusions: MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis., (© 2024. The Author(s).)

Background: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects., Methods and Results: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination., Conclusion: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma., (© 2024. The Author(s).)

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH., (© 2024. The Author(s).)

Background: At present, the implementation of intensity-modulated radiation therapy (IMRT) treatment planning for geometrically complex nasopharyngeal carcinoma (NPC) through manual trial-and-error fashion presents challenges to the improvement of planning efficiency and the obtaining of high-consistency plan quality. This paper aims to propose an automatic IMRT plan generation method through fluence prediction and further plan fine-tuning for patients with NPC and evaluates the planning efficiency and plan quality., Methods: A total of 38 patients with NPC treated with nine-beam IMRT were enrolled in this study and automatically re-planned with the proposed method. A trained deep learning model was employed to generate static field fluence maps for each patient with 3D computed tomography images and structure contours as input. Automatic IMRT treatment planning was achieved by using its generated dose with slight tightening for further plan fine-tuning. Lastly, the plan quality was compared between automatic plans and clinical plans., Results: The average time for automatic plan generation was less than 4 min, including fluence maps prediction with a python script and automated plan tuning with a C# script. Compared with clinical plans, automatic plans showed better conformity and homogeneity for planning target volumes (PTVs) except for the conformity of PTV-1. Meanwhile, the dosimetric metrics for most organs at risk (OARs) were ameliorated in the automatic plan, especially D max of the brainstem and spinal cord, and D mean of the left and right parotid glands significantly decreased (P < 0.05)., Conclusion: We have successfully implemented an automatic IMRT plan generation method for patients with NPC. This method shows high planning efficiency and comparable or superior plan quality than clinical plans. The qualitative results before and after the plan fine-tuning indicates that further optimization using dose objectives generated by predicted fluence maps is crucial to obtain high-quality automatic plans., (© 2024. The Author(s).)

Background: The career intentions of students play a crucial role in shaping the growth of the hospitality and tourism industry. Previous research underlines the significance of future work self in predicting outcomes related to one's career. However, there is limited knowledge regarding the precise ways, timing, and conditions under which the future work self of undergraduate students can enhance their employability., Methods: This paper aims to address the existing research gap by employing career construction theory and self-determination theory to propose a moderated mediation model-i.e., career exploration serves as a mediator and job market knowledge functions as a moderator in the relationship between future work self and employability. We conducted two independent studies (i.e., an experimental study and a time-lagged field study) to test the proposed model. Specifically, in Study 1 we employed an experimental research design to recruit 61 students majoring in tourism management to participate. They were randomly assigned to two scenarios (future work self: high vs. low), and we manipulated different levels of future work self by means of scenario descriptions. In Study 2, we used the time-lagged research design to collect data via submitting questionnaires among 253 Chinese undergraduates who majored in hospitality and tourism at a university in the middle area of China., Results: The results indicate a positive correlation between undergraduates' future work self and their employability. Furthermore, this relationship is mediated by a mediator of career exploration. It is important to note that this mediating relationship is also contingent upon the moderator variable of undergraduates' job market knowledge when considering the impact of career exploration on employability., Conclusion: The findings contribute to enriching the current understanding of the positive effects of future work self on undergraduates' desirable outcomes in employability., (© 2024. The Author(s).)

Objective: To explore the changes and potential mechanisms of microbiome in different parts of the upper airway in the development of pediatric OSA and observe the impact of surgical intervention on oral microbiome for pediatric OSA., Methods: Before adeno-tonsillectomy, we collected throat swab samples from different parts of the oropharynx and nasopharynx of 30 OSA patients and 10 non-OSA patients and collected throat swab samples from the oropharynx of the above patients one month after the adeno-tonsillectomy. The 16 S rRNA V3-V4 region was sequenced to identify the microbial communities. The correlation analysis was conducted based on clinical characteristics., Results: There was a significant difference of alpha diversity in different parts of the upper airway of pediatric OSA, but this difference was not found in children with non-OSA. Beta diversity was significantly different between non-OSA and pediatric OSA. At the genus level, the composition of flora in different parts is different between non-OSA and pediatric OSA. The correlation analysis revealed that the relative abundance of Neisseria was significantly correlated with obstructive apnea hypopnea index. Furthermore, the functional prediction revealed that pathways related to cell proliferation and material metabolism were significantly different between non-OSA and pediatric OSA. Besides, the adeno-tonsillectomy has minimal impact on oral microbiota composition in short term., Conclusion: The changes in upper airway microbiome are highly associated with pediatric OSA. The relative abundance of some bacteria was significantly different between OSA and non-OSA. These bacteria have the potential to become new diagnostic and early warning biomarkers., (© 2024. The Author(s).)

Background: There is substantial evidence to support the use of several methods for preventing deep-vein thrombosis (DVT) following intracerebral hemorrhage (ICH). However, the extent to which these measures are implemented in clinical practice and the factors influencing patients' receipt of preventive measures remain unclear. Therefore, we aimed to evaluate the rate of the early implementation of DVT prophylaxis and the factors associated with its success in patients with ICH., Methods: This study enrolled 49,950 patients with spontaneous ICH from the Chinese Stroke Center Alliance (CSCA) between August 2015 and July 2019. Early DVT prophylaxis implementation was defined as an intervention occurring within 48 h after admission. Univariate and multivariate logistic regression analyses were conducted to identify the rate and factors associated with the implementation of early prophylaxis for DVT in patients with ICH., Results: Among the 49,950 ICH patients, the rate of early DVT prophylaxis implementation was 49.9%, the rate of early mobilization implementation was 29.49%, and that of pharmacological prophylaxis was 2.02%. Factors associated with an increased likelihood of early DVT prophylaxis being administered in the multivariable model included receiving early rehabilitation therapy (odds ratio [OR], 2.531); admission to stroke unit (OR 2.231); admission to intensive care unit (OR 1.975); being located in central (OR 1.879) or eastern regions (OR 1.529); having a history of chronic obstructive pulmonary disease (OR 1.292), ischemic stroke (OR 1.245), coronary heart disease or myocardial infarction (OR 1.2); taking antihypertensive drugs (OR 1.136); and having a higher Glasgow Coma Scale (GCS) score (OR 1.045). Conversely, being male (OR 0.936), being hospitalized in tertiary hospitals (OR 0.778), and having a previous intracranial hemorrhage (OR 0.733) were associated with a lower likelihood of early DVT prophylaxis being administered in patients with ICH., Conclusions: The implementation rate of early DVT prophylaxis among Chinese patients with ICH was subpar, with pharmacological prophylaxis showing the lowest prevalence. Various controllable factors exerted an impact on the implementation of early DVT prophylaxis in this population., (© 2024. The Author(s).)

Background: Alzheimer's disease (AD) is a neurodegenerative disorder and the predominant type of dementia worldwide. It is characterized by the progressive and irreversible decline of cognitive functions. In addition to the pathological beta-amyloid (Aβ) deposition, glial activation, and neuronal injury in the postmortem brains of AD patients, increasing evidence suggests that the often overlooked vascular dysfunction is an important early event in AD pathophysiology. Vascular endothelial growth factor (VEGF) plays a critical role in regulating physiological functions and pathological changes in blood vessels, but whether VEGF is involved in the early stage of vascular pathology in AD remains unclear., Methods: We used an antiangiogenic agent for clinical cancer treatment, the humanized monoclonal anti-VEGF antibody bevacizumab, to block VEGF binding to its receptors in the 5×FAD mouse model at an early age. After treatment, memory performance was evaluated by a novel object recognition test, and cerebral vascular permeability and perfusion were examined by an Evans blue assay and blood flow scanning imaging analysis. Immunofluorescence staining was used to measure glial activation and Aβ deposits. VEGF and its receptors were analyzed by enzyme-linked immunosorbent assay and immunoblotting. RNA sequencing was performed to elucidate bevacizumab-associated transcriptional signatures in the hippocampus of 5×FAD mice., Results: Bevacizumab treatment administered from 4 months of age dramatically improved cerebrovascular functions, reduced glial activation, and restored long-term memory in both sexes of 5×FAD mice. Notably, a sex-specific change in different VEGF receptors was identified in the cortex and hippocampus of 5×FAD mice. Soluble VEGFR1 was decreased in female mice, while full-length VEGFR2 was increased in male mice. Bevacizumab treatment reversed the altered expression of receptors to be comparable to the level in the wild-type mice. Gene Set Enrichment Analysis of transcriptomic changes revealed that bevacizumab effectively reversed the changes in the gene sets associated with blood-brain barrier integrity and vascular smooth muscle contraction in 5×FAD mice., Conclusions: Our study demonstrated the mechanistic roles of VEGF at the early stage of amyloidopathy and the protective effects of bevacizumab on cerebrovascular function and memory performance in 5×FAD mice. These findings also suggest the therapeutic potential of bevacizumab for the early intervention of AD., (© 2024. The Author(s).)

Pathological neovascularization is a pivotal biological process in wet age-related macular degeneration (AMD), retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR), in which macrophages (Mφs) play a key role. Tip cell specialization is critical in angiogenesis; however, its interconnection with the surrounding immune environment remains unclear. Succinate is an intermediate in the tricarboxylic acid (TCA) cycle and was significantly elevated in patients with wet AMD by metabolomics. Advanced experiments revealed that SUCNR1 expression in Mφ and M2 polarization was detected in abnormal vessels of choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models. Succinate-induced M2 polarization via SUCNR1, which facilitated vascular endothelial cell (EC) migration, invasion, and tubulation, thus promoting angiogenesis in pathological neovascularization. Furthermore, evidence indicated that succinate triggered the release of RBP4 from Mφs into the surroundings to regulate endothelial sprouting and pathological angiogenesis via VEGFR2, a marker of tip cell formation. In conclusion, our results suggest that succinate represents a novel class of vasculature-inducing factors that modulate Mφ polarization and the RBP4/VEGFR2 pathway to induce pathological angiogenic signaling through tip cell specialization., (© 2023. The Author(s).)

Background: The durable oocyst wall formed from the contents of wall-forming bodies (WFBs) protects Eimeria parasites from harsh conditions and enhances parasite transmission. Comprehending the contents of WFBs and proteins involved in oocyst wall formation is pivotal to understanding the mechanism of the oocyst wall formation and the search for novel targets to disrupt parasite transmission., Methods: Total proteins extracted from WFBs and the oocyst wall of Eimeria necatrix were subjected to comparative proteomic analysis using tandem mass tag in conjunction with liquid chromatography tandem-mass spectrometry techniques. After functional clustering analysis of the identified proteins, three proteins, including E. necatrix disulfide isomerase (EnPDI), thioredoxin (EnTrx) and phosphoglycerate kinase (EnPGK), were selected for further study to confirm their potential roles in oocyst wall formation., Results: A total of 3009 and 2973 proteins were identified from WFBs and the oocyst wall of E. necatrix, respectively. Among these proteins, 1102 were identified as differentially expressed proteins, of which 506 were upregulated and 596 downregulated in the oocyst wall compared to the WFBs. A total of 108 proteins, including compositional proteins of the oocyst wall, proteases, oxidoreductases, proteins involved in glycosylation, proteins involved in synthesis of the acid-fast lipid layer and proteins related to transport, were proposed to be involved in oocyst wall formation. The approximate molecular sizes of native EnPDI, EnTrx and EnPGK proteins were 55, 50 and 45 kDa, respectively. EnPDI was present in both type 1 and type 2 WFBs, EnTrx was present only in type 2 WFB2 and EnPGK was present only in type 1 WFBs, whereas all of them were localized to the outer layer of the oocyst wall, indicating that all of them participate in the formation of the oocyst wall., Conclusions: To the best of our knowledge, this is the first report on the proteomes of WFBs and the oocyst wall of E. necatrix. The data obtained from this study form a basis for deciphering the molecular mechanisms underlying oocyst wall formation of Eimeria parasites. They also provide valuable resources for future studies on the development of novel therapeutic agents and vaccines aimed at combating coccidian transmission., (© 2023. The Author(s).)

Background: It has previously been proven that circadian rhythm disruption is associated with the incidence and deterioration of several tumors, which potentially leads to increased tumor susceptibility and a worse prognosis for tumor-bearing patients. However, their potential role in osteosarcoma has yet to be sufficiently investigated., Methods: Transcriptomic and clinical data of 84 osteosarcoma samples and 70 normal bone tissue samples were obtained from the TARGET and GTEx databases, circadian rhythm-related genes were obtained from Genecards, and circadian rhythm-related lncRNAs (CRLs) were obtained by Pearson correlation analysis, differential expression analysis, and protein-protein interaction (PPI) analysis. COX regression and LASSO regression were performed on the CRLs in order to construct a circadian rhythm-related prognostic prediction signature (CRPS). CRPS reliability was verified by Kaplan-Meier (KM), principal component analysis (PCA), nomogram, and receiver operating characteristic (ROC) curve. CRPS effects on the immune microenvironment of osteosarcoma were explored by enrichment analysis and immune infiltration analysis, and the effect of critical gene RP11-414H17.5 on osteosarcoma was experimentally verified., Result: CRPS consisting of three CRLs was constructed and its area under the curve (AUC) values predicted that osteosarcoma prognosis reached 0.892 in the training group and 0.843 in the test group, with a p value of < 0.05 for the KM curve and stable performance across different clinical subgroups. PCA analysis found that CRPS could significantly distinguish between different risk subgroups, and exhibited excellent performance in the prediction of the immune microenvironment. The experiment verified that RP11-414H17.5 can promote metastasis and inhibit apoptosis of osteosarcoma cells., Conclusion: The study revealed that circadian rhythm plays a crucial role in osteosarcoma progression and identified the impact of the key gene RP11-414H17.5 on osteosarcoma, which provides novel insights into osteosarcoma diagnosis and therapy., (© 2023. The Author(s).)

Background: Metabolomics is a tool to study the pathogenesis of diseases and their associated metabolites, but there are still insufficient metabolomic studies on severe knee osteoarthritis.To investigate the differences in serum metabolites between healthy populations and knee osteoarthritis (KOA) patients in Southern China using widely targeted metabolomics, and to explore biomarkers and their metabolic pathways that could be associated with the severity of KOA., Methods: There were 10 healthy individuals in the control group and 32 patients with KOA. According to the Kellgren-Lawrence (KL) grading system, KOA was further divided into mild (n = 13, KL grade 1 and 2) and severe (n = 19, KL grade 3 and 4). Serum samples from all participants were collected and analyzed metabolomics based on ultra-performance liquid chromatography/electrospray ionization/tandem mass spectrometry. We screened for differential metabolites between patients and controls, and between mild and severe KOA. We explored the metabolic pathways involved in differential metabolism using the Kyoto Encyclopedia of Genes and Genomes database., Results: Sixty-one metabolites were differentially expressed in the sera of the patient group compared with the control group (45 upregulated and 16 downregulated). Analysis of the mild and severe KOA groups showed a total of 12 differential metabolites. Receiver operating characteristic curve analysis showed N-alpha-acetyl-L-asparagine was a good predictor of advanced osteoarthritis(OA).Differential metabolites are enriched in multiple pathways such as arachidonic acid metabolism., Conclusion: Widely targeted metabolomics found that upregulation of the amino acid metabolite N-α-acetyl-L-asparagine was significantly associated with severe KOA and could be a biomarker for predicting severity of KOA. Arachidonic acid metabolism may play an important role in patients with severe KOA., (© 2023. The Author(s).)

Objective: To evaluate the effect and influence of the "immersive contextualization-based learning" teaching mode (ICBLT) in the orthopaedic musculoskeletal disorder module of clinical medicine education., Methods: Undergraduate students in five consecutive semesters of clinical medicine in West China Hospital, Sichuan University were enrolled in this study. During the teaching process in each semester, a cross-over design was applied, and students were randomly divided into two classes (Class A and Class B) to receive the designated experimental courses with different routes. After they took the final exams, the scores of the selected chapters (sports injury chapter and osteoarthritis chapter) were extracted to conduct Tests of Between-Subjects Effects. Q-Q plot was drawn to test whether the distribution of the scores follows normal distribution. The part of the feedback questionnaires to assess these two teaching modes were also extracted for comparison., Results: A total of 441 students were enrolled in this study, among which, Class A teaching route was implemented to 222 students and Class B to the rest 219. The results of Tests of Between-Subjects Effects showed that ICBLT mode could lead to better scores compared to the Lecturing-based learning teaching (LBLT) mode (p < 0.0001). In terms of mastery of practical skills, help to deepen the memory of knowledge and satisfaction with the teaching mode, the ICBLT mode showed better results (p < 0.0001)., Conclusion: ICBLT mode had better potential in helping mastery of practical skills and deepening the memory of knowledge., (© 2023. The Author(s).)