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Background: The lymph node ratio (LNR) has been recognized as an emerging prognostic biomarker in various malignant tumors. Our study aimed to investigate the prognostic role of LNR in postoperative patients with lymph node-positive bladder cancer., Methods: This study comprised a total of 3911 eligible patients diagnosed with lymph node-positive bladder cancer. This included 3767 patients from the Surveillance, Epidemiology, and End Results (SEER) database and 144 patients from two Chinese hospitals forming the external validation cohort. We used X-tile software to identify the optimal cut-off value for LNR. The Kaplan-Meier method and Cox regression model were utilized to evaluate the association between LNR and overall survival (OS) and cancer-specific survival (CSS). Based on the LNR index, two nomograms were constructed to estimate the prognosis of patients with lymph node-positive bladder cancer. The discriminant ability and accuracy of the nomogram were tested using the receiver operating characteristic (ROC) curve, calibration curves and decision curve analysis., Results: The Kaplan-Meier survival curves, stratified by LNR, demonstrated significant differences in overall and cancer-specific survival rates (P < 0.05). After adjusting for clinical and tumor factors, including AJCC N staging, patients with an LNR greater than 0.3 exhibited significantly worse OS and CSS compared to those with an LNR less than 0.1 in both the SEER and external validation cohorts. Furthermore, the nomogram, which incorporated LNR, showed satisfactory discriminative ability, and the calibration curves confirmed favorable consistency., Conclusion: LNR proves to be an independent prognostic factor for postoperative patients with lymph node-positive bladder cancer. These findings highlight LNR's potential as a prognostic indicator, which could be beneficial in patient consultations and guiding treatment decisions., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the First and Second Affiliated Hospital of Nanchang University. All methods were carried out in accordance with the Helsinki Declaration and approved guidelines. The Ethics Committee of the First and Second Affiliated Hospital of Nanchang University agreed to exempt patients from signing informed consent forms based on personal identity information not included. The data registered in this study was obtained from the publicly accessible SEER database, therefore there are no local or national ethical issues. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Epicardium, the most outer mesothelium, exerts crucial functions in fetal heart development and adult heart regeneration. Here we use a three-step manipulation of WNT signalling entwined with BMP and RA signalling for generating a self-organized epicardial organoid that highly express with epicardium makers WT1 and TCF21 from human embryonic stem cells. After 8-days treatment of TGF-beta following by bFGF, cells enter into epithelium-mesenchymal transition and give rise to smooth muscle cells. Epicardium could also integrate and invade into mouse heart with SNAI1 expression, and give birth to numerous cardiomyocyte-like cells. Single-cell RNA seq unveils the heterogeneity and multipotency exhibited by epicardium-derived-cells and fetal-like epicardium. Meanwhile, extracellular matrix and growth factors secreted by epicardial organoid mimics the ecology of subepicardial space between the epicardium and cardiomyocytes. As such, this epicardial organoid offers a unique ground for investigating and exploring the potential of epicardium in heart development and regeneration., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Megalobrama amblycephala presents unsynchronized growth, which affects its productivity and profitability. The liver is essential for substance exchange and energy metabolism, significantly influencing the growth of fish., Results: To investigate the differential metabolites and genes governing growth, and understand the mechanism underlying their unsynchronized growth, we conducted comprehensive transcriptomic and metabolomic analyses of liver from fast-growing (FG) and slow-growing (SG) M. amblycephala individuals. A total of 2,097 differentially expressed genes (DEGs) were identified between FG and SG, with 830 genes exhibiting significantly higher expression level in FG. KEGG and GO enrichment analysis indicated that the DEGs with higher expression level were significantly correlated with insulin signaling pathway, steroid hormone and lipid metabolism related pathway (PPAR signaling pathway and fatty acid degradation). In the metabolomic analysis, 224 differentially expressed metabolites (DEMs) were detected, of which 128 were significantly more abundant in FG. These more abundant DEMs were prominently enriched in pathways associated with cell proliferation and energy metabolism (Oxidative phosphorylation, mTOR signaling pathway and FoxO signaling pathway). In addition, DEGs and DEMs in adenosine diphosphate (ATP) hydrolysis activity and associate with fatty acid metabolism, glucose metabolism, and amino acid metabolism pathways were both found in the transcriptomic and metabolomic integrated data. These findings suggest that the large amounts of energy generated by fatty acid, glucose metabolism and other energy metabolism pathway promote the rapid growth of FG., Conclusions: This research is the first to integrate metabolomic and transcriptomic analyses of liver to identify key genes, metabolites, and pathways to uncover the molecular and metabolic mechanisms of unsynchronized growth in M. amblycephala. The identified metabolic and genes can be potential targets for selective breeding programs to improve growth performance in aquaculture., Competing Interests: Declarations. Ethics approval and consent to participate: The animal experiments conducted in this research received ethical approval from the Animal Experimental Ethical Inspection of the Laboratory Animal Center at Huazhong Agricultural University in Wuhan, China (HZAUDO-2016-005, dated 26 October 2016). All experimental protocols were executed in strict conformity with the appropriate guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Despite the increasing body of evidence that mitochondrial activities implicate in chronic obstructive pulmonary disease (COPD), we are still far from a causal-logical and mechanistic understanding of the mitochondrial malfunctions in COPD pathogenesis., Results: Differential expression genes (DEGs) from six publicly available bulk human lung tissue transcriptomic datasets of COPD patients were intersected with the known mitochondria-related genes from MitoCarta3.0 to obtain mitochondria-related DEGs associated with COPD (MitoDEGs). The 32 hub MitoDEGs identified from protein-protein interaction (PPI) networks demonstrated superior overall diagnostic efficacy to non-hub MitoDEGs. Random forest (RF) analysis, least absolute shrinkage and selection operator (LASSO) regression, and Mendelian Randomization (MR) analysis of hub MitoDEGs further nominated NDUFS2, CAT, and MRPL2 as causal MitoDEGs for COPD, whose predominate expressions in pulmonary macrophages were revealed by an independent single-cell transcriptomic dataset of COPD human lungs. Finally, NDUFS2 was evaluated as the top-ranked contributor to COPD in the nomogram model and its downregulation in pulmonary macrophages could result in pro-inflammatory secretion, enhanced intercellular communications, whereas depressed phagocytosis of macrophages as revealed by gene set variation analysis (GSVA) and cell-cell interaction (CCI) analysis of single-cell transcriptomic dataset of COPD human lungs, which was later confirmed in COPD mouse model and macrophage cell lines., Conclusions: Our study established the causal linkage between mitochondrial malfunctions and COPD, providing a potential therapeutic avenue to alleviate pulmonary inflammation accounting for COPD by targeting mitochondria-related genes. NDUFS2, a canonical component of mitochondrial electron respiratory chain, was highlighted instrumental for the susceptibility of risk-exposed individuals to COPD., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Institutional Animal Care and Use Committee at Nanjing Medical University (approval number SYXK-2023-0029) and conformed to the ARRIVE guidelines. All datasets and summarized statistics utilized in the MR analyses were generated by previous studies, for which ethical approval and individual consent were obtained for all original studies. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Folpet is a nonspecific sulfonamide fungicide widely used to protect crops from mildew. However, the in vivo effects of folpet on glucose metabolism homeostasis, gut microbiota, and abundance of drug resistance genes remain unknown. The purpose of this study was to assess the effects of the pesticide, folpet, on glucose metabolism homeostasis, and folpet-induced changes in the intestinal microbiota and resistance genes in mice., Methods: Mice were orally administered folpet at 0, 1, 10, and 100 mg/kg body weight/day for 5 weeks. Blood sugar levels in mice were measured after 5 weeks of folpet administration. Metagenomic sequencing and drug resistance gene analyses were performed to explore changes in the abundance of gut microbiota members and drug resistance genes in mice after folpet administration. Correlation analysis was performed using metabolomics to explore the relationship between intestinal microbiota, drug resistance genes, and glucose metabolism., Results: Mice in the folpet group had significantly lower blood glucose levels than those in the control group. The abundance of Atopobium, Libanicoccus, Collinsella, and Parabacteroides in the intestinal microbiota of folpet-treated mice was significantly higher than that in the control group. However, the abundance of Mailhella, Bilophila, Roseburia, and Bacteroides were reduced in folpet-treated mice. Compared with the control group, the abundance of APH6-Ic and AAC6-Ie-APH2-Ia resistance genes in mice treated with folpet significantly increased. The abundance of tetQ, ermE, and BahA resistance genes was significantly reduced after folpet treatment., Conclusions: Folpet is associated with changes in the abundance of gut microbiota in mice and may also affect the abundance of drug-resistance genes and the regulation of blood glucose levels., Competing Interests: Declarations. Ethical approval: All animal experiments were approved by the TopBiotech Animal Care and Use Committee (TOP-IACUC-2021-0082) and were conducted in accordance with the ARRIVE guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study is aimed to compare the differences in clinical outcomes between the crossed rod configuration and the parallel rod configuration applied in posterior occipitocervical and atlantoaxial fixations, and to assess the clinical applicability of crossed rods., Methods: From January 2015 to December 2021, 21 patients with craniocervical junction disorders were treated surgically with the crossed rod technique (CR group). Meanwhile, 27 corresponding patients treated with the conventional parallel rod technique were included as control (PR group). Clinical data, internal fixation type, neurological status, clinical symptoms relief, image parameter, complications and bone fusion conditions were retrospectively analyzed and evaluated., Results: No statistically significant differences were found in baseline characteristics, fixation type and postoperative complications between the two groups. Although the postoperative ADI was significantly reduced in both groups, the ADI was significantly greater in the CR group than that in the PR group after surgery and at the final follow-up (P < 0.05). All patients achieved bone fusion at 1-year postoperative follow-up except for one case in the PR group. However, patients in the CR group had a significantly higher fusion rate than those in the PR group at 3 months postoperatively (P < 0.05)., Conclusions: The application of a crossed rod configuration in posterior occipitocervical and atlantoaxial fixations provides good clinical applicability. Although this technique has a relatively weaker reduction force, it has greater fixation stability and a higher rate of early bone fusion. This technique could be an easy and viable alternative to the current parallel rod configuration for upper cervical surgery., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethical Review Committee of General Hospital of Southern Theatre Command of Peoples Liberation Army (2024012), People’s Republic of China. The data are anonymous, and the requirement for informed consent was therefore waived. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Viola diffusa is used in the formulation of various Traditional Chinese Medicines (TCMs), including antiviral, antimicrobial, antitussive, and anti-inflammatory drugs, due to its richness in flavonoids and triterpenoids. The biosynthesis of these compounds is largely mediated by cytochrome P450 enzymes, which are primarily located in the membranes of mitochondria and the endoplasmic reticulum., Results: This study presents the complete assembly of the mitogenome and plastome of Viola diffusa. The circular mitogenome spans 474,721 bp with a GC content of 44.17% and encodes 36 unique protein-coding genes, 21 tRNA, and 3 rRNA. Except for the RSCU values of 1 observed for the start codon (AUG) and tryptophan (UGG), the mitochondrial protein-coding genes exhibited a codon usage bias, with most estimates deviating from 1, similar to patterns observed in closely related species. Analysis of repetitive sequences in the mitogenome demonstrated potential homologous recombination mediated by these repeats. Sequence transfer analysis revealed 24 homologous sequences shared between the mitogenome and plastome, including nine full-length genes. Collinearity was observed among Viola diffusa species within the other members of Malpighiales order, indicated by the presence of homologous fragments. The length and arrangement of collinear blocks varied, and the mitogenome exhibited a high frequency of gene rearrangement., Conclusions: We present the first complete assembly of the mitogenome and plastome of Viola diffusa, highlighting its implications for pharmacological, evolutionary, and taxonomic studies. Our research underscores the multifaceted importance of comprehensive mitogenome analysis., Competing Interests: Declarations. Ethics approval and consent to participate: The collection and cultivation of V. diffusa complied with relevant institutional, national, and international guidelines and legislation. The V. diffusa plants used in this experiment were grown in the Baishajiang area in Shuangpai County, Yongzhou, Hunan Province, China. Ethical approval or consent was not required for this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Extracorporeal membrane oxygenation (ECMO) is mainly used for support of patients with cardiopulmonary collapse. The increasing use of ECMO has shown promising outcomes; however, it still carries the risk of significant complications. Inferior vena cava (IVC) thrombosis is an underestimated complication., Methods: We described a series of 5 ECMO patients diagnosed with IVC thrombosis in our institution. An electronic literature search of the PubMed, Cochrane Library and Web of Science databases. A total of 12 cases were identified., Results: The occurrence of IVC thrombosis in ECMO patients is not uncommon. In our case series, elevated CRP and PCT levels and activated partial thromboplastin times (aPTT) of less than 50 s during ECMO operation were observed. In the literature review, a higher proportion of veno-arterial (VA) ECMO application (67%; 8/12) was presented in patients with IVC thrombosis. Eight patients (73%; 8/11) were monitored for anticoagulation using either aPTT or a combination of aPTT and ACT, with all aPTT measurements achieving the target range for anticoagulation. The mainstay of treatment for IVC thrombosis was anticoagulation alone (75%; 9/12). After the treatment, IVC thrombosis disappeared in the majority of patients (75%; 9/12) and there was no thrombosis-related mortality., Conclusion: Factors such as elevated CRP and PCT levels, low aPTT levels, and the use of VA ECMO may contribute to the development of ECMO-related IVC thrombosis. Monitoring of anticoagulation with aPTT alone or in combination with ACT during ECMO may have inherent limitations. Anticoagulation alone may be an effective treatment for IVC thrombosis., Competing Interests: Declarations. Ethics approval and consent to participate: All procedures complied with the tenets of the Helsinki Declaration, and approved by the Institutional Review Boards of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, with approval number 2024–0479. The requirement for written informed consent was waived, owing to the non-interventional and retrospective nature of the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study utilizes a Knowledge, Attitude, and Practice (KAP) questionnaire to investigate the awareness of medical professionals in the Ningxia region regarding research integrity and their attitudes towards academic misconduct. A comprehensive analysis of the factors contributing to academic misconduct is performed, with the aim of providing insights for the formulation of policies to enhance research integrity., Methods: This study is a cross-sectional study. It performed between May 2023 and October 2023, and the questionnaires were distributed and collected through Wenjuanxing and WeChat platforms. The research employs a self-designed KAP survey questionnaire distributed online for clinical doctors and nurses in hospital, faculty members in medical higher education institutions, and undergraduates enrolled in medical schools in the Ningxia region., Results: A total of 1013 valid questionnaires were collected, with a majority of participants (76.2%) having received training in research integrity. The survey results indicate that a significant majority of participants (75.04%) cannot tolerate academic misconduct. More than 70% of respondents believe that the main reasons for academic misconduct are a lack of understanding of academic ethical norms, a deficiency in personal integrity awareness, individual inadequacy in research capabilities, and excessive pressure. When it comes to measures for academic misconduct reduction, over 70% of individuals believe that strengthening research integrity training, improving the assessment methods for research outcomes, and enhancing personal research capabilities can decrease instances of academic misconduct. Most respondents demonstrated a basic understanding of research integrity and maintained a resistant attitude towards academic misconduct. However, there exists an insufficient awareness of certain forms of academic misconduct. The study recommends implementing multifaceted measures to enhance the ethical awareness and attitudes of researchers., Conclusion: In this study, a KAP questionnaire was administered to clinicians, nurses, medical faculty and students to find out their understanding of research integrity and their attitudes towards academic misconduct. Most of the respondents had a negative attitude towards academic misconduct, but their understanding of research integrity could be improved. Furthermore, university teachers' understanding of research integrity and their attitudes towards academic misconduct were better than other groups, and university students had lower scores in this area, so it is recommended to take various measures to improve their understanding of research integrity., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval for this study was obtained from the ethics review committee of Ningxia Medical University General Hospital. (approval number: KYLL-2024-0544) Consent for publication: Consent for publication was obtained from the participants involved in this study. Competing interests: The authors declare no competing interests. Authors’ contributions: Yiran Jin: Writing – Original draft, Conceptualization, Data curation. Jie Wei: Conceptualization, Investigation. Dan Liu: Funding acquisition, Writing – review & editing, Project administration. Sang Luo: Writing – review & editing, Project administration. Liwei Yuan: Validation. Jingyi Zhang: data analysis. Xiaojie Zou: data analysis. Author Yiran Jin and Author Jie Wei share first authorship. All authors read and approved the final manuscript., (© 2024. The Author(s).)

Background: Zika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus infection., Methods: Using a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-β (IFNβ-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment efficacy., Results: Our findings demonstrated that intravenous administration of IFNβ-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-β treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFNβ-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral replication., Conclusions: Our study demonstrated that the EVs produced by IFNβ-treated MSCs could effectively convey antiviral activity., Competing Interests: Declarations Ethics approval and consent to participate All animal experimental protocols were approved by the Nanjing University Animal Care Committee and followed the ‘Guide for the Care and Use of Laboratory Animals’ published by the Chinese National Institutes of Health. And the approval number is No: IACUC-D2202180, the date of approval was January 2023. The research protocols were conducted in accordance with the animal behavioral guidelines, using approved protocols from the institutional animal care committee. For umbilical cord mesenchymal stem cells (HucMSCs) collection, the study entitled “Stem cells are extracted from clinical patient samples (tissues, blood, body fluids) and aborted fetal tissues for basic regenerative medicine and clinical disease treatment research” was approved by the Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School (Date: 11. 29. 2023, No.2017-161-08) and was conducted following approved institutional guidelines. Written informed consent was obtained from all donors prior to this study. Competing interests The authors declare that they have no competing interests. The authors declare that artificial intelligence is not used in this study., (© 2024. The Author(s).)

Background: No specific triglyceride-lowering therapy is recommended in patients with hypertriglyceridemia-associated acute pancreatitis (HTG-AP), primarily because of the lack of quality evidence. This study aimed to describe practice variations in triglyceride-lowering therapies for early HTG-AP patients and assess whether more rapid triglyceride decline is associated with improving organ failure., Methods: This is a multicentre, prospective cohort study recruiting HTG-AP patients with elevated plasma triglyceride (> 11.3 mmol/L) admitted within 72 h from the onset of symptoms. Patients were dichotomised on study day 3 into either target reaching (plasma triglyceride ≤ 5.65 mmol/L) or not. The primary outcome was organ failure-free days (OFFD) to 14 days of enrolment. The association between target-reaching and OFFD was modelled. Additionally, the slope in plasma triglyceride over the first three days in response to treatment was calculated, and its association with OFFD was assessed as a sensitivity analysis., Results: Among the 300 enrolled patients, 211 underwent exclusive medical treatment, and 89 underwent various blood purification therapies. Triglyceride levels were available in 230 patients on study day 3, among whom 122 (53.0%) had triglyceride levels of ≤ 5.65 mmol/l. The OFFD was not different between these patients and those in whom plasma triglyceride remained > 5.65 mmol/L [median (IQR): 13 (10-14) vs. 14 (10-14), p = 0.46], even after adjustment for potential confounders. For the decline slopes, there was no significant change in OFFD with a steeper decline slope [risk difference, - 0.088, 95% CI, - 0.334 to 0.158, p = 0.48]., Conclusions: Triglyceride-lowering therapies vary greatly across centres. More rapid triglyceride decline was not associated with improving incidence and duration of organ failure., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the ethics committee of Jinling Hospital (ethical number: 2020NZKY-016–01) and registered with the Chinese Clinical Trial Registry (ChiCTR2000039541). The local hospital ethics committees of all the participating sites also approved the trial. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background and Aims: Continuous vegetable production under plastic tunnels faces challenges like soil degradation, increased soil-borne pathogens, and diminished eggplant yield. These factors collectively threaten the long-term sustainability of food security by diminishing the productivity and resilience of agricultural soils. This research examined the use of raw garlic stalk (RGS) waste and arbuscular mycorrhizal fungi (AMF) as a sustainable solution for these issues in eggplant monoculture. We hypothesized that the combined application of RGS waste and AMF would improve soil physicochemical properties compared to untreated soil in eggplant monoculture. The combined use of RGS and AMF was expected to suppress soil-borne pathogens, increase the abundance of soil beneficial microorganisms and alter fungal community structure. The combined application of RGS and AMF will significantly enhance eggplant yield compared to untreated plots. This study aimed to determine whether AMF and RGS, individually or in combination, can ameliorate the adverse effects of monoculture on eggplant soil. We also investigated whether these treatments could enhance eggplant yield., Methods: The experiment was arranged in a completely randomized design with four treatments: AMF, RGS, and a combined treatment of AMF + RGS (ARGS), along with a control. Each treatment was replicated three times, Eggplant seedlings inoculated with AMF and treated with RGS amendments, both individually and combined. The effects on root traits, soil physicochemical properties, soil enzyme activity, and fungal community structure were investigated., Results: RGS amendments and AMF inoculation improved root length, volume, and mycorrhizal colonization. The combined treatment showed the most significant improvement. RGS and AMF application increased soil nutrient availability (N, P, K) and organic matter content. Enzyme activities also increased with RGS and AMF treatments, with the combined application showing the highest activity. Soil electrical conductivity (EC) increased, while soil pH decreased with RGS and AMF amendments. Sequencing revealed a shift in the fungal community structure. Ascomycota abundance decreased, while Basidiomycota abundance increased with RGS and AMF application. The combined treatment reduced the abundance of pathogenic genera (Fusarium) and enriched beneficial taxa (Chaetomium, Coprinellus, Aspergillus). Pearson correlations supported the hypothesis that soil physicochemical properties influence fungal community composition., Conclusions: This study demonstrates the potential of co-applying RGS and AMF in continuous cropping systems. It enhances soil physicochemical properties, reduces soil-borne pathogens, and promotes beneficial microbial communities and eggplant yield. This combined approach offers a sustainable strategy to address the challenges associated with eggplant monoculture under plastic tunnels., Competing Interests: Declarations Ethics declarations We declare that the manuscript reporting the research does not involve human subjects, data, or tissue. Therefore, it is not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: We explored the efficacy and safety of esketamine combined with propofol for conscious sedation in painless colonoscopy., Methods: A total of 195 patients who underwent painless colonoscopy surgery were randomly divided into three groups: the propofol deep sedation group (group DS), the sufentanil combined with propofol for conscious sedation (group CS 1 ) and the esketamine combined with propofol for conscious sedation (group CS 2 ). The primary outcomes of this study included the incidence of hypoxemia, hypotension, hypertension, and bradycardia and excellent and good rates of anaesthesia during colonoscopy. The secondary outcomes included perioperative changes in vital signs (MAP, HR, and SpO 2 ), anaesthesia induction time, dischargeable time, patient and endoscopist satisfaction scores, and incidence of postoperative nausea and vomiting (PONV), drowsiness, dizziness, propofol injection pain, assisted ventilation and vasoactive medications., Results: The incidence of intraoperative hypoxemia in the DS group was significantly greater than that in the CS 1 and CS 2 groups (χ2 = 7.081, P = 0.029). The incidence of hypotension in the CS 2 group was significantly lower than that in the DS and CS 1 groups (χ2 = 16.278, P < 0.001). The risk of hypoxemia was 5.727 times higher in Group DS than in Group CS 2 (OR 5.727; 95%CI 1.203-27.273), and the risk of hypotension was 9.864 times higher in Group DS than in Group CS 2 (OR 9.864; 95%CI 2.770-35.120). The risk of hypotension in Group CS 1 was 5.167 times that in Group CS 2 (OR 5.167; 95%CI 1.396-19.117). The incidence of propofol injection pain, assisted ventilation, ephedrine usage and drowsiness in the DS group was significantly greater than that in the CS 1 and CS 2 groups (χ2 = 57.618, P < 0.001; χ2 = 9.544, P = 0.008; χ2 = 14.820, P = 0.001; χ2 = 37.257, P < 0.001). The incidence of dizziness during recovery in the CS 1 group was significantly greater than that in the DS and CS 2 groups (χ2 = 6.594, P = 0.037). The dischargeable time in the DS group was significantly greater than that in the CS 1 and CS 2 groups (F = 53.039, P < 0.001). The satisfaction scores of the endoscopist and patients in the DS group were significantly lower than those in the CS 1 and CS 2 groups (F = 17.390, P < 0.001; F = 19.282; P < 0.001)., Conclusions: In conclusion, esketamine combined with propofol for conscious sedation can be safely and effectively used for painless colonoscopy and has fewer complications.It is recommended for painless colonoscopy., (© 2024. The Author(s).)

Background: Gesture difficulties have been reported in later-born siblings of children with autism spectrum disorder (ASD). Careful observation of gesture development during the first two years of children at elevated likelihood (EL) of developing ASD may identify behavioral indicators that facilitate early diagnosis., Methods: This study enrolled 47 EL infants and 27 low-likelihood (LL) infants to explore gesture developmental trajectories and the predictive value of gesture to expedite the early detection of core characteristics of ASD. Gesture frequency, communication function, and integration ability were observed and coded from a semi-structured assessment administered longitudinally across 9-19 months of age. We conducted the Autism Diagnostic Observation Schedule assessment at 18-19 months for ASD's core characteristics., Results: The development of joint attention (JA) gestures was slower in the EL than in the LL group. The trajectories of the two groups began to diverge at 14-18 months. Children who reached the diagnostic cutoff point for ASD showed reductions in social interaction gestures at 12-13 months, in gestures integrated with any two communication skills (G-M) at 15-16 months; and in gestures integrated with eye contact (G-E) at 18-19 months. Overall gesture and G-M integration were associated with an overall ADOS communication and social interaction score., Conclusions: The developmental trajectories of JA gestures of EL and LL children differed. G-M gestures represent early indicators that may be a predictor of ASD., (© 2024. The Author(s).)

Background: The inflammatory microenvironment plays an essential role in bone healing after fracture. The signaling lymphocytic activation molecule family (SLAMF) members deeply participate in inflammatory response and make a vast difference., Methods: We identified SLAMF8 in GEO datasets (GSE129165 and GSE176086) and co-expression analyses were performed to define the relationships between SLAMF8 and osteogenesis relative genes (RUNX2 and COL1A1). In vitro, we established SLAMF8 knockdown and overexpression mouse bone marrow mesenchymal stem cells (mBMSCs) lines. qPCR, Western blot, ALP staining, ARS staining, Oil Red O staining and Immunofluorescence analyses were performed to investigate the effect of SLAMF8 in mBMSCs osteogenesis and adipogenesis. In vivo, mice femoral fracture model was performed to explore the function of SLAMF8., Results: SLAMF8 knockdown significantly suppressed the expression of osteogenesis relative genes (RUNX2, SP7 and COL1A1), ALP activity and mineral deposition, but increased the expression of adipogenesis relative genes (PPARγ and C/EBPα). Additionally, SLAMF8 overexpression had the opposite effects. The role SLAMF8 played in mBMSCs osteogenic and adipogenic differentiation were through S100A6 and Wnt/β-Catenin signaling pathway. Moreover, SLAMF8 overexpression mBMSCs promoted the healing of femoral fracture., Conclusions: SLAMF8 promotes osteogenesis and inhibits adipogenesis of mBMSCs via S100A6 and Wnt/β-Catenin signaling pathway. SLAMF8 overexpression mBMSCs effectively accelerate the healing of femoral fracture in mice., (© 2024. The Author(s).)

Background: Ferroptosis, a non-apoptotic form of regulated cell death, plays a critical role in the suppression of various tumor types, including ovarian cancer. Artesunate (ART), a derivative of artemisinin, exhibits extensive antitumor effects and is associated with ferroptosis. This study aimed to investigate the mechanisms through which ART induces ferroptosis to inhibit ovarian cancer., Methods: RNA sequencing was conducted to identify differentially expressed genes associated with ART-induced ferroptosis. Dual-luciferase reporter assays and electrophoretic mobility shift assays were performed to confirm the interaction between Homeobox C11 (HOXC11) and the Prominin 2 (PROM2) promoter. Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays were used to analyze the antitumor effects of ART. Western blot, biochemical assays and transmission electron microscope were utilized to further characterize ART-induced ferroptosis. In vivo, the effects of ART on ferroptosis were examined using a xenograft mouse model., Results: RNA sequencing analysis revealed that the HOXC11, PROM2 and Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) pathways were downregulated by ART. HOXC11 was found to regulate PROM2 expression by binding to its promoter directly. HOXC11 overexpression reversed ART-induced effects on ovarian cancer cell proliferation, migration, apoptosis and ferroptosis by activating the PROM2/PI3K/AKT signaling axis. Conversely, silencing PROM2 in HOXC11-overexpressing cells restored ART-induced ferroptosis and its associated antitumor effects by inhibiting the PI3K/AKT pathway. Consistently, in vivo studies using a xenograft mouse model confirmed that ART-induced tumor inhibition was mediated by ferroptosis through the suppression of the HOXC11/PROM2/PI3K/AKT pathway., Conclusion: This study identifies the HOXC11/PROM2/PI3K/AKT axis as a novel regulatory mechanism underlying ART-induced ferroptosis in ovarian cancer. Targeting the HOXC11/PROM2 axis may represent a promising therapeutic strategy for enhancing ferroptosis, offering new insights for the treatment of ovarian cancer., (© 2024. The Author(s).)

Background: Meningiomas are common central nervous system tumors, predominantly intracranial, they rarely develop extracranially. Moreover, benign meningiomas seldom metastasize., Case Presentation: This article presents a case report of a 55-year-old Chinese male patient with a primary World Health Organization grade 1 meningioma originating from the petrous apex of the temporal bone, accompanied by pulmonary metastasis. Following two incomplete resections of the primary tumor, the patient underwent radiotherapy and has since maintained a stable condition., Conclusion: The case report highlights the rare occurrence of pulmonary metastasis in a benign World Health Organization grade 1 meningioma originating from an extracranial site. It also illustrates the important role of radiotherapy in treating patients with meningioma. Additionally, a review of related literature is provided to gain insights for the diagnosis and treatment of the disease., (© 2024. The Author(s).)

Background: Obesity is accompanied by inflammation, which significantly affects the homeostasis of the immune microenvironment. Hematopoietic stem cells (HSCs), residing primarily in the bone marrow, play a vital role in maintaining and producing diverse mature blood cell lineages for the adult hematopoietic and immune systems. However, how HSCs development is affected by obese-promoting inflammation, and the mechanism by which HSC hematopoietic potency is affected by inflammatory signals originating from the obese-promoting changes on bone marrow niche remain unclear. This study elucidates the relationship between obesity-promoting inflammation and HSC fate determination., Methods: The obesity mice model was established by feeding C57BL/6J mice a high-fat diet (HFD) containing 60% kcal fat. After 6 weeks, HSCs were analyzed using flow cytometry and identified key inflammation cytokine. Transcriptome sequencing techniques were used to discern the distinct pathways in HSCs. Ultimately, confirming the biological mechanism of obesity-induced HSC fate changes via Anakinra blocking specific inflammatory signals., Results: Obesity caused by HFD changed the physical and biochemical properties of the bone marrow niche. In the HFD mice, the population of long-term HSCs in the bone marrow was decreased and facilitated HSCs differentiation towards the myeloid lineage. In addition, HFD increased expression of the inflammatory factor IL-1β in the bone marrow, and a significantly increased expression of IL-1r1 and active p38/MAPK signaling pathway were detected in the HSCs. Inhibition of IL-1β further normalized the expression of genes in p38/MAPK pathway and reversed HSC fate., Conclusions: These findings have been demonstrated that the p38/MAPK signaling pathway in HSCs is activated by elevated levels of IL-1β within the HSC niche in obese models, thereby regulating HSC differentiation. It suggested a direct link between obesity-promoting inflammation and myeloid differentiation bias of HSCs in the HFD mice., (© 2024. The Author(s).)

Background: Pancreatic adenocarcinoma (PAAD) is the most frequent kind of pancreatic cancer (PC). Recent studies suggest that lipid metabolism facilitates tumorigenesis, disease progression, and resistance to therapy by promoting lipid synthesis, accumulation, and breakdown. Thus, exploring the lipid metabolism network could unveil novel therapeutic avenues for early detection, precision medicine, and prognostication in PAAD. This project intends to develop new lipid metabolism-related biomarkers for PAAD diagnosis and investigate the link between important genes and immune cell infiltration (ICI)., Methods: Tissue samples from 20 PAAD patients and 20 healthy controls were obtained. Analysis were focused on the datasets GSE71729 and GSE16515, which include samples of PAAD (n = 161) and those from healthy human tissue (n = 61), derived from the GEO database. Knockdown of PCSK9 on PC cells were conducted by si-RNA and sh-RNA. Migration and cell functional experiments were performed to assess the role of PCSK9 in cell multiplication. Furthermore, a xenograft mouse model was employed to confirm PCSK9's function in vivo., Results: The expression level of Proprotein convertase subtilisin/kexin type 9 (PCSK9) is significantly elevated in tissues affected by PAAD when compared to normal tissues. Survival analyses indicated that increased PCSK9 levels are inversely related to overall and disease-free survival (DFS). PCSK9's functional annotation associated it with the cell cycle and metabolism, especially energy metabolism. Examination of ICI data determined that PCSK9 expression demonstrated an unambiguous association with the M0 macrophages, T follicular helper cells (Tfh), gamma delta T cells and activated DC, and an inverse relationship with Monocytes, CD8 + T cells, memory B cells, resting CD4 + memory T cells, activated NK cells and resting DC abundance. PCSK9 expression knockdown has the ability to impede PC cells' migration and proliferation., Conclusion: Our study identified PCSK9 as a critical gene in PAAD. Expression levels of PCSK9 varied between PAAD and normal samples. ROC analysis verified PCSK9's strong capacity to differentiate PC from normal samples. Importantly, PCSK9 expression was considerably elevated in PC cell lines and tissues. Furthermore, PCSK9 stimulates the migration and proliferation of tumor cells in vivo and vitro., (© 2024. The Author(s).)

Barkground: Circular RNAs (circRNAs) play important regulatory roles in a variety of biological processes in mammals. Multiple birth-traits in goats are affected by several factors, but the expression and function of circRNAs in follicular development of goats are not clear. In this study, we aimed to investigate the possible regulatory mechanisms of circRNA and collected five groups of large follicles (Follicle diameter > 6 mm) and small follicles (1 mm < Follicle diameter < 3 mm) from Leizhou goats in estrus for RNA sequencing., Results: RNA sequencing showed that 152 circRNAs were differentially expressed in small and large follicles. Among them, 101 circRNAs were up-regulated in large follicles and 51 circRNAs were up-regulated in small follicles. GO and KEGG enrichment analyses showed that parental genes of the differential circRNAs were significantly enriched in important pathways, such as ovarian steroidogenesis, GnRH signaling pathway, animal autophagy and oxytocin signalling pathway. BioSignal analysis revealed that 152 differentially expressed circRNAs could target 91 differential miRNAs including miR-101 family (chi-miR-101-3p, chi-miR-101-5p), miR-202 family (chi-miR-202-5p, chi-miR-202-3p),60 circRNAs with translation potential. Based on the predicted sequencing results, the ceRNA networks chicirc&#95;008762/chi-miR-338-3p/ARHGAP18 and chicirc&#95;040444/chi-miR-338-3p/STAR were constructed in this study. Importantly, the new gene circCFAP20DC was first discovered in goats. The EDU assay and flow cytometry results indicated that circCFAP20DC enhanced the proliferation of follicular granulosa cells(GCs). Real-time quantitative PCR and western blotting assays showed that circCFAP20DC activated the Retinoblastoma(RB) pathway and promoted the progression of granulosa cells from G1 to S phase., Conclusion: Differential circRNAs in goat size follicles may have important biological functions for follicular development. The novel gene circCFAP20DC activates the RB pathway, promoting the progression of GCs from G1 to S phase. This, in turn, enhances the proliferation of follicular GCs in goats., (© 2024. The Author(s).)

Background: Hearing loss in children and adolescents is attracting increasing attention as a growing public health problem. This study aimed to analyze the burden of hearing loss in children and adolescents from 1990 to 2021 to provide a new basis for further epidemiological research, disease prevention, and public health policy development., Methods: The prevalence and years lived with disability (YLDs) of hearing loss in children and adolescents from 1990 to 2021 at the global, regional, and national levels were extracted from the Global Burden of Disease 2021 database. The estimated annual percentage change (EAPC) was used to assess trends in prevalence and YLDs. Pearson correlation analysis was used to assess the relationships between sociodemographic index (SDI) and prevalence and YLDs., Results: In 2021, approximately 97.83 million children and adolescents under the age of 20 years were affected by hearing loss globally, resulting in approximately 3.91 million YLDs. From 1990 to 2021, the prevalence rate increased from 3537 per 100,000 to 3711 per 100,000, with an EAPC of 0.15% (95% CI: 0.12-0.17). The burden of hearing loss was greater in low-middle-SDI region and low-SDI region. Mild hearing loss accounted for 62.1% of the total cases and was the predominant type of hearing loss. Otitis media was the leading preventable cause of hearing loss, with 46.9% of hearing loss attributed to otitis media. Moreover, in children under 5 years of age, 68.7% of hearing loss was attributed to otitis media. Pearson correlation analysis revealed that the prevalence rates and YLDs rates of hearing loss were negatively correlated with the SDI (R = -0.57, P < 0.001; R = -0.64, P < 0.001)., Conclusions: The burden of hearing loss in children and adolescents has increased over the past three decades and remains high. The burden is greater in less economically developed countries or regions. Policymakers should pay attention to the increasing burden of hearing loss in children and adolescents and take targeted measures to control this burden., (© 2024. The Author(s).)

Graphene oxide (GO), beyond its specialized industrial applications, is rapidly gaining prominence as a nanomaterial for modern agriculture. However, its specific effects on seed priming for salinity tolerance and yield formation in crops remain elusive. Under both pot-grown and field-grown conditions, this study combined physiological indices with transcriptomics and metabolomics to investigate how GO affects seed germination, seedling salinity tolerance, and peanut pod yield. Peanut seeds were firstly treated with 400 mg L⁻¹ GO (termed GO priming). At seed germination stage, GO-primed seeds exhibited higher germination rate and percentage of seeds with radicals breaking through the testa. Meanwhile, omics analyses revealed significant enrichment in pathways associated with carbon and nitrogen metabolisms in GO-primed seeds. At seedling stage, GO priming contributed to strengthening plant growth, enhancing photosynthesis, maintaining the integrity of plasma membrane, and promoting the nutrient accumulation in peanut seedlings under 200 mM NaCl stress. Moreover, GO priming increased the activities of antioxidant enzymes, along with reduced the accumulation of reactive oxygen species (ROS) in response to salinity stress. Furthermore, the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) of peanut seedlings under GO priming were mainly related to photosynthesis, phytohormones, antioxidant system, and carbon and nitrogen metabolisms in response to soil salinity. At maturity, GO priming showed an average increase in peanut pod yield by 12.91% compared with non-primed control. Collectively, our findings demonstrated that GO plays distinguish roles in enhancing seed germination, mitigating salinity stress, and boosting pod yield in peanut plants via modulating multiple physiological processes., (© 2024. The Author(s).)

Background: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide., Objective: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children., Methods: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation., Results: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity., Conclusions: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile., (© 2024. The Author(s).)

Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into NAD + within the body after ingestion. NMN plays a pivotal role in several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. NMN has emerged as a key focus of research in the fields of biomedicine, health care, and food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights into the pathogenesis of age- and aging-related diseases. Given the sustained global research interest in NMN and the substantial market expectations for the future, here, we comprehensively review the milestones in research on NMN biotherapy over the past 10 years. Additionally, we highlight the current research on NMN in the field of digestive system diseases, identifying existing problems and challenges in the field of NMN research. The overarching aim of this review is to provide references and insights for the further exploration of NMN within the spectrum of digestive system diseases., (© 2024. The Author(s).)

Background: Pulmonary tuberculosis (PTB) is a prevalent chronic disease associated with a significant economic burden on patients. Using machine learning to predict hospitalization costs can allocate medical resources effectively and optimize the cost structure rationally, so as to control the hospitalization costs of patients better., Methods: This research analyzed data (2020-2022) from a Kashgar pulmonary hospital's information system, involving 9570 eligible PTB patients. SPSS 26.0 was used for multiple regression analysis, while Python 3.7 was used for random forest regression (RFR) and MLP. The training set included data from 2020 and 2021, while the test set included data from 2022. The models predicted seven various costs related to PTB patients, including diagnostic cost, medical service cost, material cost, treatment cost, drug cost, other cost, and total hospitalization cost. The model's predictive performance was evaluated using R-square (R 2 ), Root Mean Squared Error (RMSE), and Mean Absolute Error (MAE) metrics., Results: Among the 9570 PTB patients included in the study, the median and quartile of total hospitalization cost were 13,150.45 (9891.34, 19,648.48) yuan. Nine factors, including age, marital status, admission condition, length of hospital stay, initial treatment, presence of other diseases, transfer, drug resistance, and admission department, significantly influenced hospitalization costs for PTB patients. Overall, MLP demonstrated superior performance in most cost predictions, outperforming RFR and multiple regression; The performance of RFR is between MLP and multiple regression; The predictive performance of multiple regression is the lowest, but it shows the best results for Other costs., Conclusion: The MLP can effectively leverage patient information and accurately predict various hospitalization costs, achieving a rationalized structure of hospitalization costs by adjusting higher-cost inpatient items and balancing different cost categories. The insights of this predictive model also hold relevance for research in other medical conditions., (© 2024. The Author(s).)

Background: Microbiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules., Methods: This was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve., Results: A total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826)., Conclusion: EBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB., (© 2024. The Author(s).)

This study examined whether maternal depression is related to Early Childhood Developmental (ECD) delay among children by quantifying the mediating contribution of responsive caregiving. We used data from 1235 children (Children's mean age = 50.4 months; 582 girls, 653 boys, 93.9% were Han), selected through convenience sampling, in 2021. 4.7% of children had ECD delay, 34.3% of mothers had depression. Children with depressed mothers were less likely to receive responsive caregiving (OR 4.35, 95% CI 2.60-7.27), and those who did not receive responsive caregiving were more likely to experience ECD delay (OR 3.89, 95% CI 1.89-8.02). Responsive caregiving partly mediated the relationship between maternal depression and ECD. Early intervention for children with depressed mothers is worthy of further investigation., (© 2024. The Author(s).)

Background: Nursing students are faced with multiple challenges and have a higher probability of suffering from anxiety. The current study aims to explore the relation between empathy and anxiety, examining the mediation and moderation effects of insomnia and self-compassion, respectively., Methods: This study employed a convenient sampling method, recruiting 1,161 nursing students (female = 923, male = 238, Mean age  = 18.37, SD age  = 2.38) from three universities in China. These students completed the questionnaires online, including General Anxiety Disorder -7 (GAD-7), Jefferson Scale of Physician Empathy-Nursing student (JSPE-NS), Youth Self-rating Insomnia Scale -8 (YSIS-8), and Self-Compassion Scale (SCS). The study employed latent variable structural equation models to analyze the relation and mechanisms between empathy and anxiety. Then, the mediated role of insomnia and the moderated role of self-compassion were examined., Results: The prevalence rates of anxiety and insomnia in the current sample are 18.24% and 26.76%, respectively. The results showed that empathy could negatively predict anxiety, with a significant mediating effect of insomnia between them (B = -0.081, p < 0.05, 95% CI [-0.197, -0.063]). Additionally, it was proven that self-compassion moderated the positive relation between insomnia and anxiety. With a higher level of self-compassion, the indirect effect of empathy on anxiety through insomnia was weaker (B = -0.053, p < 0.01, 95% CI [-0.095, -0.019]). When individuals showed a lower level of self-compassion, the indirect effect of empathy on anxiety through insomnia was stronger (B = -0.144, p < 0.01, 95% CI [-0.255, -0.059])., Conclusion: The analysis of this research proved that empathy was negatively related to anxiety, and insomnia served as a mediator between empathy and anxiety. Besides, the protective role of self-compassion on individuals' mental health was identified. The findings of the study suggest that the education of nursing students should highlight the significance of fostering empathy and self-compassion. The intervention on insomnia may be helpful in reducing the levels of anxiety since insomnia is a risky factor for anxiety., (© 2024. The Author(s).)

Background: The causal relationship between daytime napping and the risk of Parkinson's disease (PD) remains unclear, with prospective studies providing limited evidence. This study investigated the association between daytime napping frequency and duration and PD incidence and explored the causality relationship between this association by conducting Mendelian randomization (MR) analysis., Methods: This prospective cohort study included 393,302 participants, and accelerometer-measured daytime napping data were available only for 78,141 individuals. Cox proportional hazards regression was used to estimate the association between the daytime napping frequency and duration and the PD risk. The role of the systemic immune-inflammation index (SII) in the association between daytime napping frequency and PD risk was assessed through mediation analyses. Moreover, the causal association between the daytime napping frequency and the PD risk was preliminarily explored by conducting two-sample MR analyses., Results: The median follow-up duration was 12.18 years. The participants who reported napping sometimes or usually exhibited a significantly higher PD risk than those who never/rarely napped during the day [sometimes: hazard ratio (HR), 1.13; 95% confidence interval (CI), 1.03-1.23; usually: HR, 1.33; 95% CI, 1.14-1.55], and SII played a mediating role in this association. However, the MR analyses did not indicate that the daytime napping frequency and PD risk were significantly associated. The participants napping for over 1 h exhibited a significantly elevated PD risk (HR, 1.54; 95% CI, 1.11-2.16). Moreover, no significant interaction was identified between napping frequency or duration and genetic susceptibility to PD (P for interaction > 0.05)., Conclusions: In this study, increased daytime napping frequency and duration were associated with an increased PD risk, but no causal relationship was observed between napping frequency and PD risk in the MR analysis. Larger GWAS-based cohort studies and MR studies are warranted to explore potential causal relationships., (© 2024. The Author(s).)

Background: Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action., Methods: The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation., Results: DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein-protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions., Conclusion: This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action., (© 2024. The Author(s).)

Lactylation, an emerging post-translational modification, plays a pivotal role in the initiation and progression of digestive system tumors. This study presents a comprehensive review of lactylation in digestive system tumors, underscoring its critical involvement in tumor development and progression. By focusing on metabolic reprogramming, modulation of the tumor microenvironment, and the molecular mechanisms regulating tumor progression, the potential of targeting lactylation as a therapeutic strategy is highlighted. The research reveals that lactylation participates in gene expression regulation and cell signaling by affecting the post-translational states of histones and non-histone proteins, thereby influencing metabolic pathways and immune evasion mechanisms in tumor cells. Furthermore, this study assesses the feasibility of lactylation as a therapeutic target, providing insights for clinical treatment of gastrointestinal cancers. Future research should concentrate on elucidating the mechanisms of lactylation, developing efficient lactylation inhibitors, and validating their therapeutic efficacy in clinical trials, which could transform current cancer treatment and immunotherapy approaches. In summary, this review emphasizes the crucial role of lactylation in tumorigenesis and progression through a detailed analysis of its molecular mechanisms and clinical significance., (© 2024. The Author(s).)

Background: Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes., Methods: Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes., Results: Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes., Conclusions: High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management., (© 2024. The Author(s).)

Objective: Autologous iliac bone is commonly used as a bone graft material to achieve solid fusion in craniocervical junction (CVJ) surgery. However, the developing iliac bone of children is less than ideal as a bone graft material. The matured rib bone of children presents a potential substitute material for iliac bone. The aim of this study was to evaluate the efficacy of autologous rib grafts for craniocervical junction surgery in children., Methods: The outcomes of 10 children with abnormalities of the craniocervical junction who underwent craniocervical junction surgery between January 2020 and December 2022 were retrospectively reviewed. All patients underwent posterior fusion and internal fixation surgery with autologous rib grafts. Pre- and post-operative images were obtained and clinical follow-ups were conducted to evaluate neurological function, pain level, donor site complications, and bone fusion rates., Results: All surgeries were successful. During the 8- to 24-month follow-up period, all patients achieved satisfactory clinical results. Computed tomography at 3-6 months confirmed successful bone fusion and regeneration of the rib defect in all patients with no neurological or donor site complications., Conclusion: Autologous rib bone is a safe and effective material for bone grafting in craniocervical junction fusion surgery for children that can reduce the risks of donor site complications and increase the amount of bone graft, thereby achieving a higher bone fusion rate., (© 2024. The Author(s).)

Background: Malassezia restricta, a lipophilic and lipodependent yeast belonging to the basidiomycetes group, is an opportunistic fungal pathogen associated with various skin diseases, including seborrheic dermatitis and dandruff. Typically, Malassezia infection in neonates manifests as fungemia or hematogenous dissemination to the bone or lungs. However, vertebral osteomyelitis caused by these fungi is rarely reported owing to non-specific clinical presentations and laboratory/imaging findings. The Pathogen Metagenomics Sequencing (PMseq) technique enables direct high-throughput sequencing of infected specimens, facilitating the rapid and accurate detection of all microorganisms in clinical samples through comprehensive reports., Case Presentation: A 52-year-old male was admitted to our hospital on July 20, 2022 with a 3-month history of ambulatory difficulties and localized low back pain. Magnetic Resonance Imaging (MRI) examination of the spinal column revealed irregular bone destruction affecting the L2, L3, and L5 vertebral bodies. Additionally, low T1 and high T2 intensity lesions were observed at the intervertebral discs between L3 and L5. The presumptive diagnosis of tuberculous spondylitis was made based on the imaging findings, despite negative results in all mycobacterium tests. However, the patient exhibited no improvement after receiving regular anti-tuberculosis treatment for 3 months. Subsequent MRI revealed an expansive abnormal signal within the vertebral body, leading to progressive bone destruction. The absence of spinal tuberculosis or other infective microorganisms was confirmed through culture from blood and pathological tissue from the L4 vertebral body. Subsequently, PMseq was performed on the specimens, revealing M. restricta as the predominant pathogen with the highest relative abundance value. The pathological examination revealed the presence of fungal mycelium in the L4 vertebral body, with positive findings on periodic Schiff-methenamine and periodic acid-Schiff staining. The anti-tuberculosis treatment was discontinued, and an antifungal combination of fluconazole and voriconazole was administered. All symptoms were resolved after 7 consecutive months of treatment, and the patient was able to ambulate autonomously. Vertebral lesions were reduced on MRI during the 13-month follow-up., Conclusions: M. restricta is not a commonly recognized pathogen associated with infectious vertebral osteomyelitis. However, PMseq can aid in diagnosis, timely treatment, and decision making for some non-specific infectious diseases., (© 2024. The Author(s).)

The importance of the immune microenvironment in poorly cohesive carcinoma (PCC) has been highlighted due to its limited response rate to conventional therapy and emerging treatment resistance. A combination of clinical cohorts, bioinformatics analyses, and functional/molecular experiments revealed that high infiltration of Interferon Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) + tumor-associated neutrophils (TANs) is a distinguishing feature of PCC patients. Upregulation of IFIT1 + TANs promote migration and invasion of gastric cancer (GC) cell lines (MKN45 and MKN74) and stimulates the growth of cell-derived xenograft models. Besides, by promoting macrophage secreted phosphoprotein 1 (SPP1) expression and facilitating cancer-associated fibroblast and endothelial cell recruitment and activation through TANs, IFIT1 promotes a mesenchymal phenotype, which is associated with a poor prognosis. Importantly, compared to non-PCC (NPCC), PCC tumors is more immunosuppressive. Mechanistically, IFIT1 can be stimulated by IFN-γ and contributes to the expression of Programmed Cell Death 1 Ligand (PDL1) in TANs. We demonstrated in mouse models that IFIT1 + PDL1 + TANs can induce acquired resistance to anti-PD-1 immunotherapy, which may be responsible for the difficulty of PCC patients to benefit from immunotherapy. This work highlights the role of IFIT1 + TANs in mediating the remodeling of the tumor immune microenvironment and immunotherapeutic resistance and introduces IFIT1 + TANs as a promising target for precision therapy of PCC., (© 2024. The Author(s).)

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity., (© 2024. The Author(s).)

Background: Cerebral cavernous malformations (CCMs) are vascular abnormalities associated with deregulated angiogenesis. Their pathogenesis and optimal treatment remain unclear. This study aims to investigate the molecular signatures of cuproptosis, a newly identified type of cell death, associated with CCMs development., Methods: Bulk RNA sequencing (RNA-seq) from 15 CCM and 6 control samples were performed with consensus clustering and clustered to two subtypes based on expression levels of cuproptosis-related genes (CRGs). Differentially expressed genes and immune infiltration between subtypes were then identified. Machine learning algorithms including the least absolute shrinkage and selection operator and random forest were employed to screen for hub genes for CCMs associated with cuproptosis. Furthermore, Pathway enrichment and correlation analysis were used to explore the functions of hub genes and their association with immune phenotypes in CCMs. An external dataset was then employed for validation. Finally, employing the Cellchat algorithm on a single-cell RNA-seq dataset, we explored potential mechanisms underlying the participation of these hub genes in cell-cell communication in CCMs., Results: Our study revealed two distinct CCM subtypes with differential pattern of CRG expression and immune infiltration. Three hub genes (BTBD10, PFDN4, and CEMIP) were identified and validated, which may significantly associate with CCM pathogenesis. These genes were found to be significantly upregulated in CCM endothelial cells (ECs) and were validated through immunofluorescence and western blot analysis. Single-cell RNA-seq analysis revealed the cellular co-expression patterns of these hub genes, particularly highlighting the high expression of BTBD10 and PFDN4 in ECs. Additionally, a significant co-localization was also observed between BTBD10 and the pivotal cuproptosis gene FDX1 in Mki67+ tip cells, indicating the crucial role of cuproptosis for angiogenesis in CCMs. The study also explored the cell-cell communication between subcluster of ECs expressing these hub genes and immune cells, particularly M2 macrophages, suggesting a role for these interactions in CCM pathogenesis., Conclusion: This study identifies molecular signatures linking cuproptosis to CCMs pathogenesis. Three hub genes-PFDN4, CEMIP, and BTBD10-may influence disease progression by modulating immunity. Further research is needed to understand their precise disease mechanisms and evaluate their potential as biomarkers or therapeutic targets for CCMs., (© 2024. The Author(s).)

Background: Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated., Methods: We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored., Results: Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs)., Conclusion: The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer., (© 2024. The Author(s).)

Background: As a highly heterogeneous tumor, non-small cell lung cancer (NSCLC) is famous for its high incidence and mortality worldwide. Smoking can cause genetic changes, which leading to the occurrence and progress of NSCLC. Nevertheless, the function of smoking-related genes in NSCLC needs more research., Methods: We downloaded transcriptome data and clinicopathological parameters from Gene Expression Omnibus (GEO) databases, and screened smoking-related genes. Lasso regression were applied to establish the 7-gene signature. The associations between the 7-gene signature and immune microenvironment analysis, survival analysis, drug sensitivity analysis and enriched molecular pathways were studied. Ultimately, cell function experiments were conducted to research the function of FCGBP in NSCLC., Results: Through 7-gene signature, NSCLC samples were classified into high-risk group (HRG) and low-risk group (LRG). Significant difference in overall survival (OS) between HRG and LRG was found. Nomograms and ROC curves indicated that the 7-gene signature has a stable ability in predicting prognosis. Through the analysis of immune microenvironment, we found that LRG patients had better tumor immune activation. FCGBP showed the highest mutation frequency among the seven prognostic smoking related genes (LRRC31, HPGD, FCGBP, SPINK5, CYP24A1, S100P and FGG), and was notable down-regulated in NSCLC smokers compared with non-smoking NSCLC patients. The cell experiments confirmed that FCGBP knockdown promoting proliferation, migration, and invasion in NSCLC cells., Conclusion: This smoking-related prognostic signature represents a promising tool for assessing prognosis and tumor microenvironment in smokers with NSCLC. The role of FCGBP in NSCLC was found by cell experiments, which can be served as diagnostic biomarker and immunotherapy target for NSCLC., (© 2024. The Author(s).)

Background: Woody bamboos are the only diverse large perennial grasses in mesic-wet forests and are widely distributed in the understory and canopy. The functional trait variations and trade-offs in this taxon remain unclear due to woody bamboo syndromes (represented by lignified culm of composed internodes and nodes). Here, we examined the effects of heritable legacy and occurrence site climates on functional trait variations in leaf and culm across 77 woody bamboo species in a common garden. We explored the trade-offs among leaf functional traits, the connection between leaf nitrogen (N), phosphorus (P) concentrations and functional niche traits, and the correlation of functional traits between leaves and culms., Results: The Bayesian mixed models reveal that the combined effects of heritable legacy (phylogenetic distances and other evolutionary processes) and occurrence site climates accounted for 55.10-90.89% of the total variation among species for each studied trait. The standardized major axis analysis identified trade-offs among leaf functional traits in woody bamboo consistent with the global leaf economics spectrum; however, compared to non-bamboo species, the woody bamboo exhibited lower leaf mass per area but higher N, P concentrations and assimilation, dark respiration rates. The canonical correlation analysis demonstrated a positive correlation (ρ = 0.57, P-value < 0.001) between leaf N, P concentrations and morphophysiology traits. The phylogenetic principal components and trait network analyses indicated that leaf and culm traits were clustered separately, with leaf assimilation and respiration rates associated with culm ground diameter., Conclusion: Our study confirms the applicability of the leaf economics spectrum and the biogeochemical niche in woody bamboo taxa, improves the understanding of woody bamboo leaf and culm functional trait variations and trade-offs, and broadens the taxonomic units considered in plant functional trait studies, which contributes to our comprehensive understanding of terrestrial forest ecosystems., (© 2024. The Author(s).)

Background: While suture anchors are widely used in medical procedures for their advantages, they can sometimes lead to complications, including anchor prolapse. This article presents a unique case of suture anchor prolapse at the base of the distal phalanx of the little finger after extensor tendon rupture reconstruction surgery., Case Presentation: A 35-year-old male, underwent extensor tendon rupture reconstruction using a non-absorbable suture anchor. After seven years the patient visited our outpatients complaining of stiffness, pain, and protrusion at the surgical site. Initial X-ray imaging suggested suggesting either a fracture of the distal phalanx or tendon adhesion but lacked a definitive diagnosis. Subsequent magnetic resonance imaging (MRI) revealed bone connectivity between the middle and distal phalanges with irregular signal shadow and unclear boundaries while maintaining a regular finger shape. MRI proved superior in diagnosing prolapsed suture anchors, marking the first reported case of its kind. Surgical intervention confirmed MRI findings., Conclusions: Suture anchor complications, such as prolapse, are a concern in medical practice. This case underscores the significance of MRI for accurate diagnosis and the importance of tailored surgical management in addressing this uncommon complication., (© 2024. The Author(s).)

Cat scratch disease (CSD) is caused by Bartonella henselae (B. henselae) and presents as lymphadenopathy following close contact with cats. However, in context of the global COVID-19 pandemic, clinical manifestations of CSD may vary, posing new challenges for healthcare professionals. Here we describe a case of a 54-year-old male with painful left upper arm mass, which gradually resolved until he was infected with COVID-19. The mass then rapidly progressed before admission. Meanwhile, pulmonary symptoms including pleural effusion emerged simultaneously. The cause was undetermined with routine blood culture and pathological test until the next generation sequencing (NGS) confirmed the presence of B. henselae. We believe this case is the first to report localized aggravation of CSD after COVID-19 infection and hopefully, offers treatment experience for clinicians worldwide., (© 2024. The Author(s).)

Background: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear., Methods: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models., Results: PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8 + T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy., Conclusions: PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC., (© 2024. The Author(s).)

Background: 1p/19q co-deletion in low-grade gliomas (LGG, World Health Organization grade II and III) is of great significance in clinical decision making. We aim to use radiomics analysis to predict 1p/19q co-deletion in LGG based on amide proton transfer weighted (APTw), diffusion weighted imaging (DWI), and conventional MRI., Methods: This retrospective study included 90 patients histopathologically diagnosed with LGG. We performed a radiomics analysis by extracting 8454 MRI-based features form APTw, DWI and conventional MR images and applied a least absolute shrinkage and selection operator (LASSO) algorithm to select radiomics signature. A radiomics score (Rad-score) was generated using a linear combination of the values of the selected features weighted for each of the patients. Three neuroradiologists, including one experienced neuroradiologist and two resident physicians, independently evaluated the MR features of LGG and provided predictions on whether the tumor had 1p/19q co-deletion or 1p/19q intact status. A clinical model was then constructed based on the significant variables identified in this analysis. A combined model incorporating both the Rad-score and clinical factors was also constructed. The predictive performance was validated by receiver operating characteristic curve analysis, DeLong analysis and decision curve analysis. P < 0.05 was statistically significant., Results: The radiomics model and the combined model both exhibited excellent performance on both the training and test sets, achieving areas under the curve (AUCs) of 0.948 and 0.966, as well as 0.909 and 0.896, respectively. These results surpassed the performance of the clinical model, which achieved AUCs of 0.760 and 0.766 on the training and test sets, respectively. After performing Delong analysis, the clinical model did not significantly differ in predictive performance from three neuroradiologists. In the training set, both the radiomic and combined models performed better than all neuroradiologists. In the test set, the models exhibited higher AUCs than the neuroradiologists, with the radiomics model significantly outperforming resident physicians B and C, but not differing significantly from experienced neuroradiologist., Conclusions: Our results suggest that our algorithm can noninvasively predict the 1p/19q co-deletion status of LGG. The predictive performance of radiomics model was comparable to that of experienced neuroradiologist, significantly outperforming the diagnostic accuracy of resident physicians, thereby offering the potential to facilitate non-invasive 1p/19q co-deletion prediction of LGG., (© 2024. The Author(s).)

Background: Nurses with a strong professional self-concept tend to exhibit a positive mindset and strong work engagement, delivering high-quality patient care. Although numerous quantitative studies have examined the factors impacting professional self-concept, there remains a limited exploration of these factors from the perspective of nurses themselves., Methods: This qualitative descriptive study uses the PERMA theory and Social Cognitive Theory as the theoretical framework. Semi-structured interviews were conducted with 15 nurses from six public hospitals in China. The data were analyzed thematically using a combination of inductive and deductive approaches., Results: Nurses' understanding of professional self-concept could be divided into four categories: professional identity, competence, care, and knowledge. Factors influencing nurses' professional self-concept were categorized into eight subthemes in three domains: (1) personal factors, including psychological qualities and attitude towards the nursing profession; (2) occupational-related behavioral factors, including role-oriented behavior and knowledge-oriented behavior; and (3) work environment and external factors, including external evaluation and perceptions of nurses, time allocation, nursing work tasks, work atmosphere, school education, and perceived supports., Conclusions: This study found that, although nurses had different personal experiences, their perceptions of professional self-concept were similar. Nurses' professional self-concept is a multidimensional concept and involves various factors, such as personality, work-related characteristics, environment, and family. To thrive in a nursing career, nurses must discern the factors that can enhance or hinder their professional self-concept. By identifying and adjusting these factors, personalized support and positive interventions can be tailored to meet nurses' specific needs, which ultimately nurtures their professional development., Trial Registration: This study was registered on December 14, 2022, in the Chinese Clinical Trial Registry (ChiCTR2200066699) as part of our ongoing study., (© 2024. The Author(s).)

Objective: To investigate the status and related factors of sterilizers in dental health-care settings in Yunnan Province, with the aim of providing a theoretical basis for the health administrative department to formulate regional quality control programs and systems, proposing reasonable suggestions for optimizing the allocation of sterilizer resources in Yunnan's dental health-care settings, thereby improving resource utilization efficiency., Methods: This cross-sectional survey was conducted in 2600 dental health-care settings in Yunnan Province in March 2020. Uni-variable linear regression, multi-variable linear regression, curve fitting and threshold effect analysis were used to understand the relationship between dental units and sterilizers., Results: A total of 2600 dental health-care settings were included. The disinfection and sterilization work were mainly completed by the dental department in 1510(58.1%) institutions. 44(1.7%) institutions were not allocated sterilization equipment, and 1632 (62.8%) had only one sterilizer. The median allocation of sterilizers was 1.0. Uni-variable linear regression showed significant differences in covariates such as dental unit, dental handpiece, disinfection equipment, dentist, and dental assistant, which were more sensitive (p < 0.001) and statistically significant. The adjusted model was more stable in the multi-variable linear regression, and the differences in covariates between different settings were statistically significant. Curve fitting revealed an S-shaped curvilinear relationship between the number of dental units and sterilizers in oral healthcare settings., Conclusion: The disinfection and sterilization work was mainly completed by the dental department in dental health-care settings in Yunnan Province. Sterilizer allocation increases with the number of dental units, but some institutions have insufficient allocation of sterilizer and manpower resources, resulting in certain risks of infection control. Thus, it is necessary to strengthen supervision, inspection and regional quality control work in infection control of dentistry., (© 2024. The Author(s).)

Background: Chronic obstructive pulmonary disease (COPD) is underdiagnosed with the current gold standard measure pulmonary function test (PFT). A more sensitive and simple option for early detection and severity evaluation of COPD could benefit practitioners and patients., Methods: In this multicenter retrospective study, frontal chest X-ray (CXR) images and related clinical information of 1055 participants were collected and processed. Different deep learning algorithms and transfer learning models were trained to classify COPD based on clinical data and CXR images from 666 subjects, and validated in internal test set based on 284 participants. External test including 105 participants was also performed to verify the generalization ability of the learning algorithms in diagnosing COPD. Meanwhile, the model was further used to evaluate disease severity of COPD by predicting different grads., Results: The Ensemble model showed an AUC of 0.969 in distinguishing COPD by simultaneously extracting fusion features of clinical parameters and CXR images in internal test, better than models that used clinical parameters (AUC = 0.963) or images (AUC = 0.946) only. For the external test set, the AUC slightly declined to 0.934 in predicting COPD based on clinical parameters and CXR images. When applying the Ensemble model to determine disease severity of COPD, the AUC reached 0.894 for three-classification and 0.852 for five-classification respectively., Conclusion: The present study used DL algorithms to screen COPD and predict disease severity based on CXR imaging and clinical parameters. The models showed good performance and the approach might be an effective case-finding tool with low radiation dose for COPD diagnosis and staging., (© 2024. The Author(s).)

Background: In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified., Methods: To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis. Instrumental variables (IVs) for gut microbiota were retrieved from the MiBioGen consortium (18,340 participants). GWAS summary data for irAEs were gathered from an ICIs-treated cohort with 1,751 cancer patients. Various MR analysis methods, including inverse variance weighted (IVW), MR PRESSO, maximum likelihood (ML), weighted median, weighted mode, and cML-MA-BIC, were used. Furthermore, multivariable MR (MVMR) analysis was performed to account for possible influencing instrumental variables., Results: Our analysis identified fourteen gut bacterial taxa that were causally associated with irAEs. Notably, Lachnospiraceae was strongly associated with an increased risk of both high-grade and all-grade irAEs, even after accounting for the effect of BMI in the MVMR analysis. Akkermansia, Verrucomicrobiaceae, and Anaerostipes were found to exert protective roles in high-grade irAEs. However, Ruminiclostridium6, Coprococcus3, Collinsella, and Eubacterium (fissicatena group) were associated with a higher risk of developing high-grade irAEs. RuminococcaceaeUCG004, and DefluviitaleaceaeUCG011 were protective against all-grade irAEs, whereas Porphyromonadaceae, Roseburia, Eubacterium (brachy group), and Peptococcus were associated with an increased risk of all-grade irAEs., Conclusions: Our analysis highlights a strong causal association between Lachnospiraceae and irAEs, along with some other gut microbial taxa. These findings provide potential modifiable targets for managing irAEs and warrant further investigation., (© 2024. The Author(s).)

Background: Loneliness is a negative emotional state that can lead to physical and mental health problems. This study's objective was to acquire an in-depth understanding of the heterogeneity and the predictors of loneliness among older adults in rural China and provide valuable references for practical interventions., Methods: Older rural adults in China (N = 680) were recruited between January and April 2023. Latent profile analysis (LPA) was employed to identify subgroups of loneliness among participants. Single-factor and multinomial logistic regression analyses were conducted to investigate predictors of loneliness., Results: The loneliness of rural older adults could be divided into three subgroups: low interaction loneliness group (55.0%), moderate emotional loneliness group (31.8%), and high loneliness group (13.2%). The subgroup predictors included age, gender, religious beliefs, marital status, living alone, number of chronic diseases, and smartphone use (P < 0.05)., Conclusion: This study identified a classification pattern for loneliness among older adults in rural areas of China, revealed the characteristics of different demographic variables in loneliness categories, and highlighted the heterogeneity of loneliness in this population. It serves as a theoretical reference for formulating intervention plans aimed at addressing various loneliness categories for local rural older adults., Clinical Trial Registration: ChiCTR2300071591., (© 2024. The Author(s).)

Background: Fatty liver hemorrhagic syndrome (FLHS), a fatty liver disease in laying hens, poses a grave threat to the layer industry, stemming from its ability to trigger an alarming plummet in egg production and usher in acute mortality among laying hens. Increasing evidence suggests that the onset and progression of fatty liver was closely related to mitochondria dysfunction. Sodium butyrate was demonstrated to modulate hepatic lipid metabolism, alleviate oxidative stress and improve mitochondrial dysfunction in vitro and mice models. Nevertheless, there is limited existing research on coated sodium butyrate (CSB) to prevent FLHS in laying hens, and whether and how CSB exerts the anti-FLHS effect still needs to be explored. In this experiment, the FLHS model was induced by administering a high-energy low-protein (HELP) diet in laying hens. The objective was to investigate the effects of CSB on alleviating FLHS with a focus on the role of CSB in modulating mitochondrial function., Methods: A total of 288 healthy 28-week-old Huafeng laying hens were arbitrarily allocated into 4 groups with 6 replicates each, namely, the CON group (normal diet), HELP group (HELP diet), CH500 group (500 mg/kg CSB added to HELP diet) and CH750 group (750 mg/kg CSB added to HELP diet). The duration of the trial encompassed a period of 10 weeks., Results: The result revealed that CSB ameliorated the HELP-induced FLHS by improving hepatic steatosis and pathological damage, reducing the gene levels of fatty acid synthesis, and promoting the mRNA levels of key enzymes of fatty acid catabolism. CSB reduced oxidative stress induced by the HELP diet, upregulated the activity of GSH-Px and SOD, and decreased the content of MDA and ROS. CSB also mitigated the HELP diet-induced inflammatory response by blocking TNF-α, IL-1β, and F4/80. In addition, dietary CSB supplementation attenuated HELP-induced activation of the mitochondrial unfolded protein response (UPRmt), mitochondrial damage, and decline of ATPase activity. HELP diet decreased the autophagosome formation, and downregulated LC3B but upregulated p62 protein expression, which CSB administration reversed. CSB reduced HELP-induced apoptosis, as indicated by decreases in the Bax/Bcl-2, Caspase-9, Caspase-3, and Cyt C expression levels., Conclusions: Dietary CSB could ameliorate HELP diet-induced hepatic dysfunction via modulating mitochondrial dynamics, autophagy, and apoptosis in laying hens. Consequently, CSB, as a feed additive, exhibited the capacity to prevent FLHS by modulating autophagy and lipid metabolism., (© 2024. The Author(s).)