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Background: Smoking has been identified as a standalone risk factor for coronary heart disease (CHD) and myocardial infarction (MI), but the precise underlying mechanisms remain incompletely elucidated., Results: In this study, we conducted a two-sample Mendelian randomization analysis to examine the impact of smoking behaviors (including smoking initiation, age of smoking initiation, cigarettes per day, and smoking cessation) and smoking-related DNA methylation at CpG sites on CHD and MI based on the UK Biobank dataset. Additionally, we included the FinnGen and Biobank Japan datasets as replications and performed a meta-analysis to combine the results from different data sources. We further validated our results using genetic colocalization analysis. In genomic analysis, we provided compelling evidence on the association between genetically predicted smoking initiation and increased susceptibility to CHD and MI. In epigenetic analysis, we identified 11 smoking-related CpG sites linked to CHD risk and 10 smoking-related CpG sites associated with the risk of MI based on the UK Biobank dataset. Subsequently, some of these CpG sites were further replicated using the FinnGen or BBJ datasets. Ultimately, a meta-analysis was conducted to integrate findings from various data sources (3 for CHD, and 2 for MI), revealing that 7 of 11 CpG sites were linked to CHD risk; whereas, 7 of 10 CpG sites were associated with MI risk. Furthermore, we performed genetic colocalization analysis and found that cg19744173 (FBLN7), cg00395063 (ARHGEF12), and cg16822035 (MCF2L) exhibited robust evidence of colocalization with coronary heart disease; whereas, cg19529732 (DIABLO), cg26405020 (FES), and cg08940075 (CNN3) demonstrated strong colocalization evidence with the risk of myocardial infarction., Conclusions: Our research offers a novel insight into the impact of smoking on the susceptibility to CHD and MI through the lens of epigenetic DNA methylation., Competing Interests: Declarations. Ethics approval and consent to participate: The research adhered to the guidelines outlined in the Declaration of Helsinki. Approval from an appropriate review board was obtained for all referenced genome-wide association studies, epigenome-wide association studies, and both summary-level and individual-level data. Additionally, participants provided written informed consent. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The dose perturbation effect of immobilization devices is often overlooked in intensity-modulated radiation therapy (IMRT) for gynecologic cancer. This retrospective study assessed the dosimetric effects of a prone immobilization device combined with a belly board (PIDBB) on the skin., Methods: We recruited 63 women with gynecologic cancer undergoing postoperative IMRT at our institute. A 0.3 cm thick skin contour and body contours with or without PIDBB system were outlined for each patient. Dose calculations were performed for the two sets of contours using the same plan, named Plan - and Plan + , respectively. The accuracy of calculated doses was verified by gafchromic EBT3 film and anthropomorphic phantom., Results: The V 40 Gy , V 30 Gy , V 20 Gy , V 15 Gy and D mean of skin increased by 56.94%, 65.48%, 53.12%, 41.91%, and 1.91%, respectively. Even after excluding the effect of prescription dose coverage, the V 40 Gy , V 30 Gy , V 20 Gy , V 15 Gy and D mean of skin still increased by 46.90%, 92.07%, 72.81%, 52.25%, and 18.06%, respectively. No significant differences were observed in doses to other organs at risk. The EBT3 measurements showed that the skin dose map to the anthropomorphic phantom was 23.79% higher than that calculated by the treatment planning system without the PIDBB system., Conclusions: While the PIDBB system effectively reduces the low dose to small intestine, it also induces radiation attenuation, leading to a sharp increase in skin dose, particularly in patients receiving radiation in the groin and perineum area. Therefore, immobilization devices should be included in the external contour to account for dose attenuation and the increment in skin dose., Trial Registration: This study does not report on interventions in human health care., Competing Interests: Declarations. Ethics approval and consent to participate: As the data are anonymous and no intervention was happened in the treatment of patient, only verbal informed consent was obtained from participants, this procedure was approved by the of the Third Affiliated Hospital of Sun Yat-sen University Ethics Committee [II2023-149-01]. Consent for publication: The authors have declared that no competing interest exists. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study aims to establish EQ-5D-Y-3L population norms in Jiangsu, China by conducting a large-scale cross-sectional survey., Methods: Children and adolescents aged 9-17 from three cities of Jiangsu Province were selected by multistage stratified random sampling to complete the EQ-5D-Y-3L instrument independently. Population norms for Jiangsu, China were determined by calculating statistics based on age and gender. Logistic and Tobit regression models were employed to explain the relationship between HRQoL and factors such as sociodemographic characteristics/recent acute symptoms (experienced fever/cough/sore throat/diarrhea in the past two weeks)., Results: Three cities yielded 37,574 valid samples (a sample validity rate of 95.4%). The EQ-5D-Y-3L utility values (mean ± SD) were 0.964 ± 0.085 for males and 0.958 ± 0.077 for females. Males scored 85.94 ± 19.62 and females scored 84.83 ± 18.45 on the VAS (mean ± SD), while the percentages of respondents reporting full health ranged from 58.3 to 78.8%. The dimension in which most respondents reported having no problems was "feeling worried, sad, or unhappy" (23.0%). And the lowest HRQoL was shown in the 14-year-old age group. Gender, age, board at school, and BMI were found to have an association with HRQoL. In addition, recent acute symptoms also correlate with some aspects of HRQoL., Conclusions: This study established EQ-5D-Y-3L population norms in Jiangsu, China for the first time. These norms will support resource allocation decision-making and be used as a reference for health evaluation studies., Competing Interests: Declarations. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Ethical Review Committee of Nanjing Medical University (Ethics approval number: (661/2021)). Consent to participate: Verbal informed consent was obtained from all individual participants and their legal guardians. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Several studies reported the sterol ester (SE), a subclass of subtype of cholesterol ester (CE), is associated with the incidence of colorectal cancer (CRC). Nevertheless, the causal relationship of SE on CRC remains unknown., Methods: A two-sample Mendelian randomization study was performed with the summary statistics of SE (27:1/14:0) which is from the largest available genome-wide association study meta-analysis(n = 377277) conducted by FinnGen consortium. The summary data were obtained from UK Biobank repository (377673 cases and 372016 controls). And we used a relative relaxed filter (p < 5 × 10 - 6 and LD r 2  < 0.01) of instrumental variables to explore the causal effect and complete the sensitive analysis with the threshold p < 5 × 10 - 8 and LD r 2  < 0.01, MR Egger intercept, MR-PRESSO, and leave-one-out method, which all support the causal assessment. Inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted model, were used to examine the causal association between SE (27:1/14:0) and CRC. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables., Results: The IVW results showed that SE (27:1/14:0) (OR = 1.004; 95% CI 1.002, 1.005; p < 0.001) have genetic causal relationship with CRC. The results of weighted median, weighted mode, and simple mode are all consistent with IVW model. However, the result from the MR-Egger method (OR = 1.005; 95% CI 1.004, 1.009; p = 0.052) didn't demonstrate a significant result. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The results of MR analysis were not driven by a single SNP. And results from two filter threshold is consistent., Conclusion: Altogether, genetically predicted sterol ester (27:1/14:0) plays a causal association role in the incidence of CRC. This finding will provide a new screening and diagnosis indicator of CRC in the future., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Although many people received the COVID-19 vaccine, shortly after the Chinese government announced that the three-year COVID-19 restrictions were being eased, the first large number of Omicron infections appeared in Beijing. We describe epidemiological characteristics, clinical severity, and time-to-event distribution of patients infected with SARS-CoV-2 in Beijing Omicron outbreak, comparing those who received the booster vaccine with cases of full-course/partial-course vaccines., Methods: We collected epidemiological, clinical, laboratory, and clinical management data from the hospital information system (HIS) for 1495 cases during Dec 2022-Jan 2023. We also collected illness onset time, diagnosis time, hospital admission time, and start and end times of each treatment. In addition, we collected the time of vaccination, inoculation times, and type of COVID-19 vaccination thorough the vaccination system. We described the epidemiological characteristics across vaccine inoculation doses, and estimated the risk of death, mechanical ventilation, and admission to the intensive care unit for patients admitted to hospital. We used the Kaplan-Meier method to estimate the survival rate and plot the survival curve, and the Cox proportional hazards model to assess the effect of covariates on survival time., Results: Of the 1495 cases, 58.1% were male. The median ages in the non-vaccinated and vaccinated groups were 80 and 47 years. Elderly with underlying medical conditions and lower BMI less willing to vaccinate(p < 0.05). Both the inactivated vaccine and adenovirus vaccine could reduce clinical severity and prolong survival time, and the protective effect of booster vaccination was the best. The clinical severity increased linearly from the booster vaccinated group to the full-course vaccinated group and non-vaccinated groups, and the death risk of COVID-19 cases without vaccination was the highest., Conclusion: Booster vaccines of COVID-19 can provide greater protection against severe illness and death, and continuous monitoring and regular assessment are needed to minimize the risk of a recurrence of the pandemic., Competing Interests: Declarations. Ethical approval: The Ethics Review Committee of the Beijing Hospital of Traditional Chinese Medicine, Capital Medical University provided approval for this study (No: 2023BL02-016-01). Patients’ personal identifying information was anonymized to ensure privacy. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The spatial layout of large-scale functional brain networks exhibits considerable inter-individual variability, especially in the association cortex. Research has demonstrated a link between early socioeconomic status (SES) and variations in both brain structure and function, which are further associated with cognitive and mental health outcomes. However, the extent to which SES is associated with individual differences in personalized functional network topography during childhood remains largely unexplored., Methods: We used a machine learning approach-spatially regularized non-negative matrix factorization (NMF)-to delineate 17 personalized functional networks in children aged 9-10 years, utilizing high-quality functional MRI data from 6001 participants in the Adolescent Brain Cognitive Development study. Partial least square regression approach with repeated random twofold cross-validation was used to evaluate the association between the multivariate pattern of functional network topography and three SES factors, including family income-to-needs ratio, parental education, and neighborhood disadvantage., Results: We found that individual variations in personalized functional network topography aligned with the hierarchical sensorimotor-association axis across the cortex. Furthermore, we observed that functional network topography significantly predicted the three SES factors from unseen individuals. The associations between functional topography and SES factors were also hierarchically organized along the sensorimotor-association cortical axis, exhibiting stronger positive associations in the higher-order association cortex. Additionally, we have made the personalized functional networks publicly accessible., Conclusions: These results offer insights into how SES influences neurodevelopment through personalized functional neuroanatomy in childhood, highlighting the cortex-wide, hierarchically organized plasticity of the functional networks in response to diverse SES backgrounds., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of the University of California, San Diego, and other relevant institutional review boards. Most ABCD research sites rely on a central Institutional Review Board (IRB) at the University of California, San Diego for the ethical review and approval of the research protocol, with a few sites obtaining local IRB approval (e.g., Washington University in St. Louis) ( https://doi.org/ https://doi.org/10.1016/j.dcn.2017.06.005 ). Parents or guardians provided written informed consent after the procedures were fully explained, and children assented prior to participation in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Orbital Castleman's disease is a rare benign lymphoproliferative disorder of extranodal origin., Case Presentation: A 72-year-old man presented with bilateral upper eyelid swelling. Radiology revealed enlarged lacrimal glands in both eyes. Castleman's disease (plasma cell type) was confirmed by histo-immunochemical examinations after excision of the left orbital mass. No extraorbital involvement was found in systemic evaluation. Postoperatively, corticosteroid therapy was given. After 1 year of follow-up, there was no recurrence in the left orbit, and the swelling of the right eyelid was improved., Conclusions: Here, we report a case of orbital Castleman's disease involving the lacrimal gland bilaterally and summarize previously reported cases. For bilateral orbital masses, the possibility of Castleman's disease should be considered. Before the diagnosis, it is necessary to fully distinguish from other diseases such as IgG4-related eye diseases., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Early detection and treatment of HIV and sexually transmitted infections (STIs) are crucial for effective control. We previously developed MySTIRisk, an artificial intelligence-based risk tool that predicts the risk of HIV and STIs. We examined the attributes that encourage potential users to use it., Methods: Between January and March 2024, we sent text message invitations to the Melbourne Sexual Health Centre (MSHC) attendees to participate in an online survey. We also advertised the survey on social media, the clinic's website, and posters in affiliated general practice clinics. This anonymous survey used a discrete choice experiment (DCE) to examine which MySTIRisk attributes would encourage potential users. We analysed the data using random parameters logit (RPL) and latent class analysis (LCA) models., Results: The median age of 415 participants was 31 years (interquartile range, 26-38 years), with a minority of participants identifying as straight or heterosexual (31.8%, n = 132). The choice to use MySTIRisk was most influenced by two attributes: cost and accuracy, followed by the availability of a pathology request form, level of anonymity, speed of receiving results, and whether the tool was a web or mobile application. LCA revealed two classes: "The Precisionists" (66.0% of respondents), who demanded high accuracy and "The Economists" (34.0% of respondents), who prioritised low cost. Simulations predicted a high uptake (97.7%) for a tool designed with the most preferred attribute levels, contrasting with lower uptake (22.3%) for the least preferred design., Conclusions: Participants were more likely to use MySTIRisk if it was free, highly accurate, and could send pathology request forms. Tailoring the tool to distinct user segments could enhance its uptake and effectiveness in promoting early detection and prevention of HIV and STIs., Competing Interests: Declarations. Ethics approval and consent to participate: This study received ethical approval from the Alfred Hospital Ethics Committee in Melbourne, Australia (project number: 637/23). All research procedures adhered to the committee's ethical standards and regulations. All participants provided informed consent at the start of the online survey. Participants could proceed with the survey only if they provided their consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hidden blood loss (HBL) is a notable complication in spinal endoscopic procedures. This study aims to compare tissue damage and hidden blood loss between two minimally invasive spinal techniques: unilateral biportal endoscopic lumbar discectomy (UBE) and percutaneous endoscopic interlaminar discectomy (PEID). Furthermore, the study examines the risk factors contributing to hidden blood loss in each procedure., Patients and Methods: A single-center retrospective cohort study was conducted on 86 patients who underwent unilateral biportal endoscopic lumbar discectomy (UBE) and 73 patients who received percutaneous endoscopic interlaminar discectomy (PEID) between January 2021 and December 2023.Demographic data, blood loss parameters, and serum levels of creatine kinase (CK) and C-reactive protein (CRP) were recorded. Pearson or Spearman correlation analyses were conducted to evaluate associations between patient characteristics and HBL. Additionally, multiple linear regression analysis was used to identify independent risk factors for HBL., Results: A total of 159 consecutive patients were included in this study, consisting of 83 females and 76 males. The average hidden blood loss (HBL) was 431.00 ± 160.52 ml in the UBE group and 328.40 ± 87.71 ml in the PEID group, showing a statistically significant difference (P < 0.05). Pearson or Spearman correlation analysis indicated that in the UBE group, HBL was associated with operation time, preoperative hematocrit (Hct), ASA classification, and paraspinal muscle thickness. In the PEID group, HBL was correlated with operation time, preoperative activated partial thromboplastin time (APTT), paraspinal muscle thickness, and the presence of diabetes (P < 0.05). Multiple linear regression analysis demonstrated a positive correlation between HBL and operation time in both groups (P < 0.05), identifying operation time as an independent risk factor for HBL. Furthermore, CRP and CK levels were generally lower in the PEID group compared to the UBE group, particularly on postoperative day 3 for CRP and postoperative day 1 for CK. Both total blood loss and hidden blood loss were significantly lower in the PEID group than in the UBE group., Conclusion: Compared to UBE, PEID shows superior results regarding surgical trauma, total blood loss, hidden blood loss (HBL), and postoperative hematocrit (Hct) reduction. Consequently, PEID is recommended as the treatment of choice for younger patients or those with compromised baseline perioperative conditions.Additionally, Hidden blood loss remains a critical factor, and surgical duration presents a shared risk in both procedures., Competing Interests: Declarations. Ethical approval: This project is supported by the 2023 Central Government-Led Local Science and Technology Development Fund, under the project “Standardization and Promotion of Single and Double-Channel Spinal Endoscopic Techniques” (Project No. 2023ZY013). This project does not involve the collection, preservation, utilization, external provision, or management of human genetic resources. Therefore, it has been exempted from ethical review by the Ethics Committee of Qinghai Red Cross Hospital. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The relationship between public health emergencies and psychological distress had been well known, yet none research had been conducted on the trend in psychological resilience and its longitudinal determinants during the pandemic. This study aimed to explore the changes of psychological resilience of university students during COVID-19 pandemic, and further clarify the longitudinal relationship between family factors, mental health, social mentality and psychological resilience., Methods: Questionnaires were distributed to students from five universities in Shandong Province, China during the COVID-19. A total of 1635 students were finally included in this three-wave follow-up study using stratified random sampling method. Mental health was assessed by Depression Anxiety Stress Scale, social mentality was measured by the Bi-Dimensional Structure Questionnaire of Social Mentality, psychological resilience was evaluated by the Chinese version of the Psychological Resilience Scale. Repeated-measures analysis of variance was used to analyze the longitudinal changes of psychological resilience, generalized estimating equation (GEE) was conducted to estimate the determinants of psychological resilience., Results: Psychological resilience changed from 28.37 in Wave 1, 29.10 in Wave 2, and 29.15 in Wave 3 among the university students. The students who majored in Art (β = 0.872, P = 0.032), parents (mother β = 0.546, P = 0.035; father β = 0.718, P = 0.012) had a greater influence on children's personality, and positive social mentality (β = 5.725, P < 0.001) were more likely to report a higher psychological resilience. Being female (β=-0.932, P < 0.001), not being a student leader (β=-0.911, P < 0.001), being anxious (β=-1.845, P < 0.001) and depressed (β=-1.846, P < 0.001), and negative social mentality (β=-0.803, P < 0.001) were less likely to report a higher psychological resilience., Conclusions: The psychological resilience of the university students in Shandong Province, China increased significantly from Wave 1 to Wave 3 during the COVID-19 pandemic. Majoring in Art, parents having a greater influence on children's personality, better mental health, positive social mentality were more likely to report a higher psychological resilience, while female, not student leader, worse mental health, and negative social mentality were less likely to report a higher the psychological resilience., Competing Interests: Declarations Ethics approval and consent to participate The study was designed in accordance with the tenets of the Declaration of Helsinki, 1996 and was approved by the ethical committee of Shandong University before data collection (Task No. LL20200201). Informed consent Informed consent was obtained from all subjects. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Melanoma, recognized as the most aggressive type of skin cancer, has experienced a notable increase in cases, especially within populations with fair skin. This highly aggressive cancer is largely driven by UV radiation exposure, resulting in the uncontrolled growth and malignant transformation of melanocytes. The cGAS-STING pathway, an immune signaling mechanism responsible for detecting double-stranded DNA in the cytoplasm, is essential for mediating the immune response against melanoma. This pathway serves a dual purpose: it enhances antitumor immunity by activating immune cells, but it can also promote tumor growth when chronically activated by creating an immunosuppressive environment. This review comprehensively examines the multifaceted implication of the cGAS-STING pathway in melanoma pathogenesis and treatment. We explore its molecular mechanisms, including epigenetic regulation, interaction with signaling pathways such as AR signaling, and modulation by various cellular effectors like TG2 and activin-A. The therapeutic potential of modulating the cGAS-STING pathway is highlighted, with promising results from STING agonists, combination therapies with immune checkpoint inhibitors, and novel drug delivery systems, including nanoparticles and synthetic drugs. Our findings underscore the importance of the cGAS-STING pathway in melanoma, presenting it as a critical target for enhancing anti-tumor immunity. By leveraging this pathway, future therapeutic strategies can potentially convert 'cold' tumors into 'hot' tumors, making them more susceptible to immune responses., Competing Interests: Declarations Ethics approval and consent to participate Not applicable (Review Study). Informed consent to consent for publication Not applicable (Review Study). Declaration of generative AI and AI-assisted technologies in the writing process During the preparation of this work, the authors used ChatGPT by OpenAI to improve paper readability. After using this tool/service, the authors reviewed and edited the content as needed and took full responsibility for the publication’s content. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To investigate the difference in bone-implant contact (BIC) and the rate of infratemporal fossa intrusion among different apex sites for quad zygomatic implants (ZIs) design in edentulous patients with severe alveolar bone resorption., Methods: Patients with maxillary edentulism were evaluated. Alveolar bone resorption was assessed using the Cawood and Howell classification. Participants with Class IV or Class V/VI bone resorption were selected. The zygomatic bone was devided into upper, middle and lower thirds, with four potential implant apex locations identified in each third. Virtual planning for quad ZIs, along with measurements of BIC were performed. Additionally, the occurrence of ZIs intrusion into the infratemporal fossa was examined, and the distance between ZI and orbital cavity was measured., Results: A total of 28 CBCT scans of edentulous patients, encompassing 56 zygomas, were analyzed. Thirty-nine single lateral posterior edentulous jaws were classified into Class IV subgroup, while 17 into Class V/IV subgroup. Among all patients and patients in subgroups, the anterior and posterior ZI exhibited the highest BIC at points A3 and B2, respectively. The average zygomatic BIC at A3 apex point was 18.3 ± 3.9 mm, and that at the B2 apex point was 16.3 ± 5.3 mm. Quad ZIs risk intrusion into the infratemporal fossa when positioned at B2, B3, and at all apex points of the lower zygoma segment. Three anterior ZIs at A3 point show less than 1 mm distance to orbital cavity. Overall, A3 and B1 apex points showed high BIC and low infratemporal intrusion rate for quad ZIs, irrespective of patient's alveolar bone resorption status., Conclusions: The optional apex point for anterior and posterior quad ZIs is A3 and B1, respectively, regardless of the patients's alveolar bone resorption level. Alveolar bone resorption does not affect the BIC for quad ZIs. Anterior ZI positioned at A3 point may present high risk for orbital penetration and may not be reccomended in a Quad ZI approach., Trial Registration: The clinical research is registered under the number ChiCTR2100044472., Competing Interests: Declarations Consent for publication Consent for publication of identifiable details, images was obtained from all individual participants. Competing interests The authors declare no competing interests. Ethics approval This study was conducted in accordance with the principles of the Declaration of Helsinki, as revised in 2013. This study received approval from the Institutional Review Board of the University (Ethical Approval No: PKUSSIRB-202162013). The clinical research is registered under the number ChiCTR2100044472., (© 2024. The Author(s).)

Background: Diabetes-associated cognitive dysfunction, characterized by hippocampal synaptic loss as an early pathological feature, seriously threatens patients' quality of life. Synapses are dynamic structures, and hormones play important roles in modulating the formation and elimination of synapses. The pituitary, the master gland of the body, releases several hormones with multiple roles in hippocampal synaptic regulation. In this study, we aimed to explore the relationship between pituitary hormones and cognitive decline in diabetes., Methods: A total of 744 patients with type 2 diabetes (T2DM) (445 men and 299 postmenopausal women) who underwent serum pituitary hormone level assessments, comprehensive cognitive evaluations and MRI scans were enrolled. Dynamic diet interventions were applied in both chow diet-fed mice and high-fat diet (HFD)-fed diabetic mice. The cognitive performance and hippocampal pathology of prolactin (PRL)-knockout mice, neuronal prolactin receptor (PRLR)-specific knockout mice and microglial PRLR-specific knockout mice were assessed. Microglial PRLR-specific knockout mice were fed an HFD to model diabetes. Diabetic mice received an intracerebroventricular infusion of recombinant PRL protein or vehicle., Results: This clinical study revealed that decreased PRL levels were associated with cognitive impairment and hippocampal damage in T2DM patients. In diabetic mice, PRL levels diminished before hippocampal synaptic loss and cognitive decline occurred. PRL loss could directly cause cognitive dysfunction and decreased hippocampal synaptic density. Knockout of PRLR in microglia, rather than neurons, induced hippocampal synaptic loss and cognitive impairment. Furthermore, blockade of PRL/PRLR signaling in microglia exacerbated abnormal microglial phagocytosis of synapses, further aggravating hippocampal synaptic loss and cognitive impairment in diabetic mice. Moreover, PRL infusion reduced microglia-mediated synaptic loss, thereby alleviating cognitive impairment in diabetic mice., Conclusion: PRL is associated with cognitive dysfunction and hippocampal damage in T2DM patients. In diabetes, a decrease in PRL level drives hippocampal synaptic loss and cognitive impairment by increasing microglia-mediated synapse engulfment. Restoration of PRL levels ameliorates cognitive dysfunction and hippocampal synaptic loss in diabetic mice., Competing Interests: Declaration Ethics approval and consent to participate The study protocols of participants was approved by the ethics committee of Nanjing Drum Tower Hospital by the Ethics Review Committee of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School (Approval number: 2017-017-01). All animal experimental procedures were conducted under the Institutional Animal Care and Use Committee-approved protocols (2005010) at Nanjing University according to Laboratory Animal Care Guidelines. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Aim: This study aimed to investigate the impact of bedside case-based learning on critical thinking and capacity for self-directed learning in a group of midwifery students in China., Background: Bedside teaching is a well-established educational tool to improve the clinical practice of medical, nursing, and midwifery students. A new pedagogical approach; bedside case-based learning (BCBL) is an interactive teaching approach involving small-group, student-educator discussion to describe the etiology and management of a patient case. This new approach has been gradually integrated into Chinese midwifery education programs to promote clinical problem-solving skills, knowledge application, teamwork, and collaboration., Design: A quasi-experimental pre-test-post-test group design., Methods: This study used a quasi-experimental pre-test-post-test group design. A convenience sample of 67 third-year students majoring in midwifery at the university were prospectively enrolled in this study. Pre- and post-BCBL class surveys were conducted using the Self-Rating Scale of Self-Directed Learning (SRSSDL) and the Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) to assess changes in self-learning and critical thinking abilities before and after the intervention., Results: Following bedside case-based learning, the total scores for self-directed learning capacity and critical thinking increased, although there were no statistically significant differences (P > 0.05)., Conclusions: Although there were no statistically significant differences between pre- and post-test results, students' self-assessed scores in self-directed learning and critical thinking improved between pre- and post-test., Competing Interests: Declarations Ethical approval and consent to participate This study was approved by the Research Ethics Committee at the Nursing School of Zhejiang Chinese Medical University and conducted according to the Helsinki Declaration. Informed consent was obtained from all the participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Decompensated cirrhosis (DC) is prone to recurrent episodes of decompensation following the initial event. This study aimed to identify the risk factors for subsequent decompensation and assess their impact on the outcomes of patients hospitalized for DC., Methods: Patients with DC were divided into two groups based on the occurrence of new decompensated events during hospitalization. Logistic regression analysis was employed to identify risk factors for new decompensation. The Cox proportional hazards model was used to evaluate the relationship between new decompensation and short-term mortality risk in these patients., Results: The study cohort consisted of 339 patients with DC, with a median age of 57 years. During hospitalization, 83 patients (24.5%) experienced new decompensated events, with bacterial infections (BIs) being the most common (n = 46, 13.6%). Multivariate analysis revealed that the Model for End-Stage Liver Disease (MELD) score at admission (OR = 1.06, 95% CI: 1.02-1.11, P = 0.005) was the sole risk factor for new decompensation during hospitalization. Patients who experienced new decompensation had significantly higher 28-day (28.9% vs. 7.0%, P < 0.001) and 90-day (33.7% vs. 15.2%, P < 0.001) transplant-free mortality compared to those who did not. After adjusting for white cell count, C-reactive protein, and MELD score, new decompensation during hospitalization was identified as an independent risk factor for 28-day and 90-day mortality (HR = 2.63, 95% CI: 1.42-4.87, P = 0.002 and HR = 1.73, 95% CI: 1.04-2.88, P = 0.033, respectively)., Conclusions: Patients with high MELD scores are susceptible to new decompensation during hospitalization, and the occurrence of new decompensation adversely affects short-term mortality in patients with DC., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval for this study (approval number: 2021 − 670) was provided by the Ethical Committee of the First Affiliated Hospital of Zhejiang University School of Medicine. Written informed consent was obtained from the patients. All research was conducted following both the Declarations of Helsinki and Istanbul. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: This study explored the effectiveness of a Problem-based Learning (PBL) teaching model on the WeChat public platform for radiation oncology residency training programs., Materials and Methods: The WeChat PBL program was initiated in 2019. The study recruited student participants, on a voluntary basis, who were in their first and second years of standardized training in radiation oncology. We selected classic and trending issues in radiation oncology as the two main teaching topics. Students in the PBL group searched for relevant literature, summarizing PowerPoint presentations or academic speeches on specific issues published on the professional WeChat public platform after an in-depth review by teachers. The final national standardized training examination scores for resident physicians were used to evaluate teaching effectiveness. The graduation scores of the PBL and non-PBL groups were compared, and a stratified analysis was conducted based on the year of participation to assess the teaching effectiveness of this model. Moreover, questionnaires were administered to evaluate students' experiences., Results: Among the 36 students who joined the study in 2019, 16 (44.0%) voluntarily joined the PBL teaching group. Nine students started teaching PBL in their first year of residency, accounting for 47.4% of that year, and seven started in their second year, accounting for 41.2%. The average graduation scores of the PBL group were superior to those of the non-PBL-focused group for the same grade. The rate of high scores among students in the PBL group (56.3%) was higher than that of students in the non-PBL group (25%). Specifically, first-year residents who joined the PBL group had an average score of 92.3 ± 2.2, significantly higher than their non-PBL counterparts, who scored an average of 88.6 ± 4.6, showing a statistically significant advantage (p = 0.042). All students were satisfied with the PBL WeChat teaching and would recommend the PBL WeChat course to others., Conclusion: The PBL residency teaching model on the WeChat platform improved residency scores and garnered student satisfaction., Competing Interests: Declarations Ethics approval and consent to participate All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Human Research Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. This study meets the requirement for exemption from informed consent to participate. Consent for publication Written informed consent for publication was obtained from all participants. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Chronic osteomyelitis with large bone defects remains a challenging condition in orthopedic surgery. This study aimed to evaluate the clinical efficacy of hemicorticotomy bone transport assisted by 3D-printed customized guides in the treatment of chronic osteomyelitis with bone defects., Methods: A retrospective analysis was conducted on 21 patients with chronic osteomyelitis treated with hemicorticotomy bone transport with 3D-printed guide assistance between January 2015 and January 2021. Preoperative planning utilized 3D CT reconstruction for precise guide design and osteotomy placement. The surgical technique involved hemicorticotomy, placement of the 3D-printed guide, and gradual bone transport using a monolateral external fixator. Clinical outcomes were assessed using the Association for the Study and Application of Methods of Ilizarov (ASAMI) scoring system. The external fixation time (EFT), external fixation index (EFI), and complications evaluated using the Paley classification were recorded., Results: The mean bone defect size was 7.9 ± 2.0 cm. The average follow-up period was 28.6 ± 6.4 months. The mean external fixation time was 289.4 ± 52.7 days, with an external fixation index of 36.8 ± 4.2 days/cm. According to the ASAMI criteria, the bone results were excellent in 17 patients (81%), good in 3 (14%), and fair in 1 (5%). The functional results were excellent in 15 patients (71%), good in 4 (19%), and fair in 2 (10%). Complete eradication of the infection and union at the docking site were achieved in all patients. The complication rate was 38% and all of which were successfully managed., Conclusion: Hemicorticotomy bone transport assisted by 3D-printed customized guides is an effective treatment for chronic osteomyelitis with bone defects. This technique offers excellent bone healing, favorable functional results, and a relatively low complication rate. Further studies with larger sample sizes are warranted to validate these findings., Competing Interests: Declarations Ethics approval and consent to participate All patients gave written informed consent before participation in this study and study protocols were approved by ethical committee of The First Affiliated Hospital of Xinjiang Medical University and The Fourth Affiliated Hospital of Xinjiang Medical University, Traditional Chinese Medicine Hospital of Xinjiang Uyghur Autonomous Region. All methods were carried out in accordance with relevant guidelines and regulation. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Triple-negative breast cancer (TNBC) continues to pose a significant obstacle in the field of oncology. Dysregulation of lipid metabolism, notably upregulated ketogenesis, has emerged as a hallmark of TNBC, yet its role in metastasis has been elusive. Here, by utilizing clinical specimens and experimental models, the study demonstrates that increased ketogenesis fosters TNBC metastasis by promoting the up-regulation of β-hydroxybutyrate (β-OHB), a key ketone body. Mechanistically, β-OHB facilitates β-hydroxybutyrylation (Kbhb) of Calpastatin (CAST), an endogenous calpain (CAPN) inhibitor, at K43, blocking the interaction with CAPN and subsequently promoting FAK phosphorylation and epithelial‒mesenchymal transition (EMT). In conclusion, the study reveals a novel regulatory axis linking ketogenesis to TNBC metastasis, shedding light on the intricate interplay between metabolic reprogramming and tumor progression., Competing Interests: Declarations Ethical approval All experiments received approval from the Clinical Trial Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (KY2024-R080) and were conducted in accordance with the Helsinki Declaration principles. Animal experiments were conducted with the approval of the Animal Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University in accordance with the Regulations on the Management of Experimental Animals. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Ages of 0-3 years are critical stages for children's neurodevelopment. However, the impact of the home nurturing environment on early childhood neurodevelopment remains unclear., Objective: To explore the role of the home nurturing environment on early childhood neurodevelopment and to provide evidence of an association between fostering quality home nurturing and achieving optimal neurodevelopment., Participants and Setting: An online cross-sectional survey using the stratified sampling method was conducted from 16 June, 2021 to 18, February, 2022 in all 13 communities of Minhang District, Shanghai. A total of 2,402 children aged 0-3 years with balanced sex distribution were included., Methods: The quality of home nurturing environments was measured using validated Child Home Nurture Environment Scales. Neurodevelopment was measured using the Ages and Stages Questionnaire - Third edition (ASQ-3). Generalized Linear Mixed Modeling was used to analyze the association between the quality of home nurturing environments and neurodevelopment., Results: Among children aged 0-1, neglect or restriction was reported as the most prevalent problem (8.02%) among home nurturing environment dimensions, and was associated with an increased risk of suspected fine motor development delay (OR = 2.82, 95% CI: 1.18-6.69, P = 0.019). Among children aged 1-3, inadequate parental warmth, as the foremost (16.10%) problem, was associated with an increased risk of suspected gross motor development delay (OR = 4.12, 95% CI: 1.35-12.53, P = 0.013) and suspected personal-social development delay (OR = 12.50, 95%CI: 1.48-105.36, P = 0.020)., Conclusions: Poor home nurturing environments were associated with an increased risk of suspected early childhood neurodevelopment delay. There exists a need for services to guide for establishing a quality home nurturing environment., Competing Interests: Declarations Ethics approval and consent to participate The ethical approval was obtained from Shanghai Minhang Maternal and Child Health Care Hospital ([2020]-KS-06). All participants in the study had been informed and consented to participate in this study. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Global warming-induced environmental stresses have diverse effects on gene expression and regulation in the life processes of various aquatic organisms. N6 adenylate methylation (m6A) modifications are known to influence mRNA transcription, localization, translation, stability, splicing, and nuclear export, which are pivotal in mediating stress responses. Apostichopus japonicus is a significant species in aquaculture and a representative of benthic organisms in ecosystems, thus there is a growing need for research on its heat stress mechanism., Results: In this study, m6A-modified whole transcriptome profiles of the respiratory tree tissues of A. japonicus in the control (T18) and high-temperature stress (T32) groups were obtained using MeRIP-seq technology. The results showed that 7,211 common m6A peaks, and 9,459 genes containing common m6A were identified in three replicates T18 and T32 groups. The m6A peaks were found to be highly enriched in the 3' untranslated region, and the common sequence of the m6A peak was also enriched, which was shown as RRACH (R = G or A; H = A, C, or U). A total of 1,200 peaks were identified as significantly differentially enriched in the T32 group compared with the T18 group. Among them, 245 peaks were upregulated and 955 were downregulated, which indicated that high temperature stress significantly altered the methylation pattern of m6A, and there were more demethylation sites in the T32 group. Conjoint analysis of the m6A methylation modification and the transcript expression level (the MeRIP-seq and RNA-seq data) showed co-differentiated 395 genes were identified, which were subsequently divided into four groups with a predominant pattern that more genes with decreased m6A modification and up-regulated expression, including HSP70IV, EIF2AK1, etc. GO enrichment and KEGG analyses of differential m6A peak related genes and co-differentiated genes showed the genes were significantly associated with transcription process and pathways such as protein processing in the endoplasmic reticulum, Wnt signaling pathway, and mTOR signaling pathway, etc. CONCLUSION: The comparisons of m6A modification patterns and conjoint analyses of m6A modification and gene expression profiles suggest that m6A modification was involved in the regulation of heat stress-responsive genes and important functional pathways in A. japonicus in response to high-temperature stress. The study will contribute to elucidate the regulatory mechanism of m6A modification in the response of A. japonicus to environmental stress, as well as the conservation and utilization of sea cucumber resources in the context of environmental changes., Competing Interests: Declarations Ethics approval and consent to participate The animal study was approved by the Institutional Animal Care and Use Committee of the Ludong University (protocol number LDU-IRB20210308NXY). The study was conducted in accordance with the local legislation and institutional requirements. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Epigenetic regulation has emerged as a promising therapeutic strategy for lung cancer treatment, which can facilitate the antitumor responses by modulating epigenetic dysregulation of target proteins in lung cancer. The proteolysis-targeting chimera (PROTAC) reagent, dBET6 shows effective inhibition of bromodomain-containing protein 4 (BRD4) that exerts antitumor efficacy by degrading BRD4 via the ubiquitin-proteasome system. Nevertheless, the low tissue specificity and bioavailability impede its therapeutic effects and clinical translation on lung cancer treatment. Herein, we developed a type of dual targeting and bioresponsive nano-PROTAC (c R GD/L LC membrane/D S-P LGA/d B ET6, named RLDPB), which was constructed by using the pH and glutathione (GSH)-responsive polymer, disulfide bond-linked poly(lactic-co-glycolic acid) (PLGA-S-S-PLGA, DS-PLGA) to load the PROTAC agent dBET6, and further camouflaged with the homotypic LLC cell membranes, followed by the conjugation with cRGD ligand to the surface of the nanoparticles. Notably, RLDPB showed enhanced celluar uptake by lung cancer cells in vitro and accumulation in the tumors via the dual targeting structure including cRGD and LLC membrane. The pH/GSH responsiveness improved the release of dBET6 from the DS-PLGA-based nanoparticles within the cells. RLDPB was demonstrated to facilitate tumor regression by inducing the apoptosis of lung cancer cells with the degradation of BRD4. Thus, RLDPB can be considered a powerful tool to suppress lung cancer, which opens a new avenue to treat lung cancer by PROTAC., Competing Interests: Declarations Ethics approval and consent to participate Animal experiments were permitted by the Institutional Animal Care and Use Committee (No. S2023-770) and performed under the guidelines of the Animal Welfare Act of Guangzhou Medical University. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Hyperlipidemia plays a crucial role in increasing the risk of cardiovascular diseases such as atherosclerosis. Recent studies have established that inclisiran positively influences lipid regulation. Nevertheless, its effectiveness in comparison to conventional treatments is still questionable. Hence, a methodical assessment of its effectiveness and safety is required. This research evaluates the efficacy and safety of inclisiran, PCSK9 inhibitors, and the combination of statins with ezetimibe in the treatment of hyperlipidemia via a network meta-analysis of randomized controlled trials (RCTs)., Methods: We performed an extensive search of English-language publications in the PubMed, Medline, Embase, and Cochrane Library databases until April 2024. We conducted a web-based meta-analysis and reported in accordance with the guidelines. We selected the percentage change in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) as efficacy evaluation metrics and the incidence of adverse events as safety evaluation metrics for analysis and comparison., Result: We incorporated 33 studies involving 23,375 patients, evaluating three interventions regarding their effects on LDL-C, TC, TG, HDL-C, and adverse events. All treatments improved metrics over placebo. Inclisiran significantly reduced LDL-C compared to statins (mean - 15.21, 95% CI [-25.19, -5.23]) but showed no significant difference from statin + ezetimibe. Surface under the cumulative ranking curve (SUCRA) rankings placed inclisiran highest for LDL-C reduction (26.2%). The combination of statin and ezetimibe was the most efficacious for triglyceride reduction (mean 17.2, 95% CI [10.22, 24.19]; mean 15.61, 95% CI [16.87, 24.35]). The safety profiles were comparable across treatments., Conclusion: Inclisiran with its superior LDL-C reduction and low frequency of administration, appears promising for hyperlipidemia treatment, particularly for patients with adherence issues or side effects from other medications., Systematic Review Registration: CRD42024550852., (© 2024. The Author(s).)

Background: Membranous nephropathy (MN) and IgA nephropathy (IgAN) pose challenges in clinical treatment with existing therapies primarily focusing on symptom relief and often yielding unsatisfactory outcomes. The search for novel drug targets remains crucial to address the shortcomings in managing both kidney diseases., Methods: Utilizing GWAS data for MN (ncase = 2150, ncontrol = 5829) and IgAN (ncase = 15587, ncontrol = 462197), instrumental variables for plasma proteins were derived from recent GWAS. Sensitivity analysis involved bidirectional Mendelian randomization analysis, MR Steiger, Bayesian co-localization, and Phenotype scanning. The SMR analysis using eQTL data from the eQTLGen Consortium was conducted to assess the availability of selected protein targets. The PPI network was constructed to reveal potential associations with existing drug treatment targets., Results: The study, subjected to the stringent Bonferroni correction, revealed significant associations: four proteins with MN and three proteins with IgAN. In plasma protein cis-pQTL data from two cohorts, an increase in one standard deviation in PLA2R1 (OR = 2.01, 95%CI = 1.83-2.21), AIF1 (OR = 9.04, 95%CI = 4.69-17.41), MLN (OR = 3.79, 95%CI = 2.12-6.78), and NFKB1 (OR = 29.43, 95%CI = 7.73-112.0) was associated with an increased risk of MN. Additionally, in plasma protein cis-pQTL data, a standard deviation increase in FCGR3B (OR = 1.15, 95%CI = 1.09-1.22) and BTN3A1 (OR = 4.05, 95%CI = 2.65-6.19) correlated with elevated IgAN risk, while AIF1 (OR = 0.58, 95%CI = 0.46-0.73) exhibited IgAN protection. Bayesian co-localization indicated that PLA2R1 (coloc.abf-PPH4 = 0.695), NFKB1 (coloc.abf-PPH4 = 0.949), FCGR3B (coloc.abf-PPH4 = 0.909), and BTN3A1 (coloc.abf-PPH4 = 0.685) share the same variants associated with MN and IgAN. The SMR analysis indicated a causal link between NFKB1 and BTN3A1 plasma protein eQTL in both conditions, and BTN3A1 was validated externally., Conclusion: Genetically influenced plasma levels of PLA2R1 and NFKB1 impact MN risk, while FCGR3B and BTN3A1 levels are causally linked to IgAN risk, suggesting potential drug targets for further clinical exploration, notably BTN3A1 for IgAN., (© 2024. The Author(s).)

Background: Radiation enteritis (RE) is a common complication of radiotherapy for abdominal and pelvic tumors, adversely affecting treatment outcomes and patients' quality of life. Gut microbiome alterations may contribute to RE development, but the underlying pathogenic factors are not fully understood. This study aimed to characterize the intestinal microbial changes associated with RE and severe acute radiation enteritis (SARE) and to identify predictive biomarkers., Methods: We enrolled 50 cervical cancer patients undergoing radiotherapy and 15 healthy women (controls). Stool samples were collected at the baseline and during weeks 2, 4, and 6 of radiotherapy, and then analyzed using 16 S rDNA sequencing and bioinformatics., Results: Although the Bacteroidetes/Firmicutes (B/F) ratio was higher in patients with RE or SARE, it alone could not predict these conditions. Three enterotypes were identified based on dominant genera: Blautia (enterotype 1), Escherichia-Shigella (enterotype 2), and Faecalibacterium (enterotype 3). A decrease in Blautia and an increase in Escherichia-Shigella and Faecalibacterium were correlated with RE and SARE. Univariate logistic regression revealed that the Faecalibacterium enterotype at the baseline was associated with a 4.4-fold higher risk of developing SARE (odds ratio 5.400; P = 0.017). The Escherichia-Shigella enterotype was also linked to increased SARE incidence., Conclusion: These findings suggest that while single bacterial genera or the B/F ratio are insufficient predictors, enterotype classification may serve as a potential biomarker for predicting SARE in patients undergoing radiotherapy., (© 2024. The Author(s).)

Background: To evaluate the clinical outcomes and the validity of the in situ needle fenestration (ISNF) technique during thoracic endovascular aortic repair (TEVAR) for patients with aortic arch conditions., Methods: A total of 115 patients with aortic arch conditions treated with ISNF during TEVAR between January 2018 and December 2021 were incorporated., Results: The median age of the patients was 62.0 years, and 10.4% (12/115) were female. The median follow-up time was 31.0 months. A total of 175 supra-arch branches were reconstructed. A single branch was fenestrated in 80 patients, while the left subclavian artery (LSA) and left common carotid artery (LCCA) were fenestrated simultaneously in 11 patients, and all supra-arch branches were fenestrated in 24 patients. The rate of technical success was 100%, 30-day mortality was 3.5% (4/115), overall mortality was 8.7% (10/115), and aortic-related mortality was 2.6% (3/115). Aortic-related reintervention was required in 7.8% (9/115) of patients. Among the major postoperative complications, four patients developed retrograde type A dissection requiring emergent open surgery, three patients had cerebrovascular accidents, and one patient had an endoleak. No occlusions or stenoses of the main or branch aortic stents were observed., Conclusions: The mid-term results of the ISNF technique during TEVAR for aortic arch conditions were within the acceptable range; however, further follow-up results are needed and long-term stability and durability needs to be assessed. Related fenestration devices also require further development., (© 2024. The Author(s).)

Background: The latest evidence on health literacy in China revealed that only 8% of individuals aged 65-69 years, a segment of the geriatric population, possess adequate health literacy levels, indicating a low level in China. Studies have demonstrated that improving the organizational health literacy of healthcare institutions is a crucial approach to addressing low health literacy among older patients., Objective: To explore the obstacles hindering the advancement of organizational health literacy in healthcare institutions in meeting the needs of older patients., Design: A mixed-methods approach was employed to investigate both the status and barriers to the establishment of organizational health literacy within two healthcare institutions., Participants: Participants included older individuals aged over 60, clinical staff, and managerial personnel from these two health institutions., Methods: This research utilized the social-ecological model as its theoretical foundation and utilized a mixed-methods approach to examine the current status and challenges in developing organizational health literacy within healthcare institutions. Initially, a survey using a questionnaire (n = 178) was conducted among older patients to evaluate the establishment of organizational health literacy from their perspective. Following this, interviews (n = 22) were carried out with administrators, clinical personnel, and elderly patients to identify the barriers hindering the development of organizational health literacy within healthcare institutions., Results: Quantitative research indicates that health institutions have been less accommodating to the requirements of older patients, with health information dissemination and communication emerging as the weakest areas. Qualitative investigations revealed three key influencing factors: patient-related factors, including physiological and cognitive decline, as well as low educational attainment among older patients; organizational factors, including inadequate clinical staff numbers, deficient long-term systematic training, and a digital divide resulting from health institutions' digital advancements; and policy-related factors indicating a lack of regulations governing the establishment of organizational health literacy within healthcare institutions., Conclusion: The two most vulnerable aspects of OHL in medical institutions regarding the needs of older patients are health information and communication. The factors influencing the construction of OHL in medical institutions are multifaceted, encompassing micro, meso, and macro levels. At the macro level, it is essential for medical institutions to enhance leadership awareness of OHL and to incorporate its development into institutional strategic plans. At the meso-level, medical institutions should be made to optimize the medical environment for elderly patients and to prioritize health literacy training for medical staff. At the micro level, attention must be given to the characteristics and needs of elderly patients. Ultimately, by implementing a comprehensive construction of intervention strategies, the response ability of medical institutions to the needs of elderly patients can be enhanced., (© 2024. The Author(s).)

Background: Ki67 index changes during the treatment of metastatic pancreatic neuroendocrine tumor (PanNET) treatment. The study aimed to detect alterations of grade based on Ki67 index and immune microenvironment in PanNET responding to capecitabine/temozolomide (CapTem)., Method: Retrospective data of patients with PanNET were collected. In control group, 35 patients underwent surgery immediately after biopsy. In CapTem group, 38 patients received CapTem after biopsy and responded well to treatment (defined as either stable disease or partial response), and subsequently underwent surgery. All patients have pathological Ki67 index at biopsy and after surgery. CD163 + CD68 + CD206 + M2 macrophages, CD68 + CD86 + CD80 + M1 macrophages, CD11b + CD33 + myeloid-derived suppressor cells, and CD4 + CD25 + regulatory T cells were stained using multiplex immunofluorescence., Results: In control group, the paired grade based on Ki67 index directly after surgery showed no upgrade or downgrade compared to biopsy. In patients who responded well to CapTem, the grade based on Ki67 index before and after CapTem was altered. Thirteen patients had upgraded Ki67 index and 11 patients had downgraded. The proportion of stable disease was higher in the upgraded group compared to downgraded group (p = 0.0155). And upgraded group had a significantly shorter mPFS than patients in the downgrade group (8.5 months vs. 20 months, HR 4.834, 95% CI 1.414 to 16.53, p = 0.012). M1 macrophages was significantly lower in the downgraded group than in the Ki67 upgraded group (p < 0.001)., Conclusion: Grade based on Ki67 index and immune environment change in PanNET patients responding well to CapTem. Patients with downgraded had longer mPFS compared to those with upgraded. It is necessary to reassess the Ki67 index after CapTem treatment, even in patients responding well to CapTem., (© 2024. The Author(s).)

Increasing evidence supports the crucial role of Epithelial-Mesenchymal Transition (EMT) in cancer invasion and metastasis. N-acetylglucosaminyltransferase V (MGAT5), which is associated with multiantenna glycosylation, can contribute to tumorigenesis, yet its specific role in promoting colorectal cancer (CRC) metastasis remains unclear. Bioinformatics analysis of CRC datasets revealed that elevated MGAT5 expression was associated with EMT and a poor prognosis. In vitro experiments confirmed the pivotal role of MGAT5 as an EMT regulator in CRC cells. MGAT5 overexpression stimulated cell proliferation and migration, while MGAT5 knockdown had the opposite effect. Mechanistically, MGAT5 promoted EMT through multiantenna glycosylation of ZO-1, promoting its ubiquitination and reducing its expression. Clinically, MGAT5 upregulation in the CRC TMA correlated negatively with ZO-1 expression, which is indicative of malignancy and a poor prognosis. This study revealed that MGAT5 promotes EMT in CRC via interactions between multiple antenna glycosylation products and ZO-1 ubiquitination/degradation, indicating that MGAT5 could serve as a promising therapeutic target for CRC., (© 2024. The Author(s).)

The genus Megalocytivirus, belonging to the family Iridoviridae, is one of the most detrimental virus groups to fish aquaculture. Megalocytivirus creates a virus-mock basement membrane (VMBM) on the surface of infected cells. This membrane provides attachment sites for lymphatic endothelial cells (LECs), disrupting fish's endothelial cell-extracellular matrix system. This disruption triggers injury to the vascular system and can result in death. Exploring the VMBM-cell interaction mechanism is crucial for uncovering the pathogenesis of Megalocytivirus and identifying therapeutic targets. Claudins, a class of tetra transmembrane proteins, play a key role in creating tight junctions between endothelial or epithelial cells. In this study, we demonstrated that the expression of Claudin2, a member of the Claudin family in fish, was significantly up-regulated by Megalocytivirus infection. Claudin2 was found in LECs attached to the surface of infected cells. It interacted with the VMBM viral components VP23R, VP08R, and VP33L at multiple binding sites through its two extracellular loops. However, it did not interact with the host basement membrane's nidogen. Therefore, Claudin2 is involved in the interaction of LEC with VMBM and plays a role in the disturbed distribution of extracellular matrix and endothelial cells in Megalocytivirus-infected fish tissues. This study aims to uncover the molecular mechanisms by which Megalocytivirus infection leads to pathological changes in the vascular system., (© 2024. The Author(s).)

Background: Although capsule endoscopy (CE) is a crucial tool for diagnosing small bowel diseases, the need to process a vast number of images imposes a significant workload on physicians, leading to a high risk of missed diagnoses. This study aims to develop an artificial intelligence (AI) model and application based on convolutional neural networks that can automatically recognize various lesions in small bowel capsule endoscopy., Methods: Three small bowel capsule endoscopy datasets were used for AI model training, validation, and testing, encompassing 12 categories of images. The model's performance was evaluated using metrics such as AUC, sensitivity, specificity, precision, accuracy, and F1 score to select the best model. A human-machine comparison experiment was conducted using the best model and endoscopists with varying levels of experience. Model interpretability was analyzed using Grad-CAM and SHAP techniques. Finally, a clinical application was developed based on the best model using PyQt5 technology., Results: A total of 34,303 images were included in this study. The best model, MobileNetv3-large, achieved a weighted average sensitivity of 87.17%, specificity of 98.77%, and an AUC of 0.9897 across all categories. The application developed based on this model performed exceptionally well in comparison with endoscopists, achieving an accuracy of 87.17% and a processing speed of 75.04 frames per second, surpassing endoscopists of varying experience levels., Conclusion: The AI model and application developed based on convolutional neural networks can quickly and accurately identify 12 types of small bowel lesions. With its high sensitivity, this system can effectively assist physicians in interpreting small bowel capsule endoscopy images.Future studies will validate the AI system for video evaluations and real-world clinical integration., (© 2024. The Author(s).)

Background: Intestinal parasitic infections are still a serious public health problem in developing countries, and the diagnosis of parasitic infections requires the first step of parasite/egg detection of samples. Automated detection can eliminate the dependence on professionals, but the current detection algorithms require large computational resources, which increases the lower limit of automated detection. Therefore, we have designed a lightweight deep-learning model, YAC-Net, to achieve rapid and accurate detection of parasitic eggs and reduce the cost of automation., Methods: This paper uses the ICIP 2022 Challenge dataset for experiments, and the experiments are conducted using fivefold cross-validation. The YOLOv5n model is used as the baseline model, and then two improvements are made to the baseline model based on the specificity of the egg data. First, the neck of the YOLOv5n is modified to from a feature pyramid network (FPN) to an asymptotic feature pyramid network (AFPN) structure. Different from the FPN structure, which mainly integrates semantic feature information at adjacent levels, the hierarchical and asymptotic aggregation structure of AFPN can fully fuse the spatial contextual information of egg images, and its adaptive spatial feature fusion mode can help the model select beneficial feature and ignore redundant information, thereby reducing computational complexity and improving detection performance. Second, the C3 module of the backbone of the YOLOv5n is modified to a C2f module, which can enrich gradient information, improving the feature extraction capability of the backbone. Moreover, ablation studies are designed by us to verify the effectiveness of the AFPN and C2f modules in the process of model lightweighting., Results: The experimental results show that compared with YOLOv5n, YAC-Net improves precision by 1.1%, recall by 2.8%, the F1 score by 0.0195, and mAP&#95;0.5 by 0.0271 and reduces the parameters by one-fifth. Compared with some state-of-the-art detection methods, YAC-Net achieves the best performance in precision, F1 score, mAP&#95;0.5, and parameters. The precision, recall, F1 score, mAP&#95;0.5, and parameters of our method on the test set are 97.8%, 97.7%, 0.9773, 0.9913, and 1,924,302, respectively., Conclusions: Compared with the baseline model, YAC-Net optimizes the model structure and simplifies the parameters while ensuring the detection performance. It helps to reduce the equipment requirements for performing automated detection and can be used to realize the automatic detection of parasite eggs under microscope images., (© 2024. The Author(s).)

Background: The production of β-lactamases is the most prevalent resistance mechanism for β-lactam antibiotics in Gram-negative bacteria. Presently, over 4900 β-lactamases have been discovered, and they are categorized into hundreds of families. In each enzyme family, amino acid substitutions result in subtle changes to enzyme hydrolysis profiles; in contrast, certain conserved sequences retained by all of the family members can serve as important markers for enzyme family identification., Results: The SHV family was chosen as the study object. First, a unique 10-mer peptide was identified as SHV family's epitope by an approach of protein fingerprint analysis. Then, an SHV-specific magnetic epitope-imprinted gel polymer (MEI-GP) was prepared by an epitope surface imprinting technique, and its sorption behavior and recognition mechanism for template epitope and SHV were both elaborated. Finally, the MEI-GP was successfully applied to selectively extract SHV from bacteria, and the extracted SHV was submitted to MALDI-TOF MS for specific determination. By following this strategy, other β-lactamase families can also be specifically detected. According to the molecular weight displayed in mass spectra, the kind of β-lactamase and its associated hydrolysis profile on β-lactams can be easily identified. Based on this, an initial drug option scheme can be quickly formulated for antimicrobial therapy. From protein extraction to medication guidance reporting, the mean time to detection (MTTD) was less than 2 h, which is much faster than conventional phenotype-based methods (at least 16-20 h) and gene-based techniques (usually about 8 h)., Conclusions: This enzyme-specific detection strategy combined the specificity of epitope imprinting with the sensitivity of mass spectrometry, enabling β-lactamase to be selectively extracted from bacteria and clearly presented in mass spectra. Compared with other drug resistance detection methods, this technique has good specificity, high sensitivity (≤ 15 mg of bacteria), a short MTTD (less than 2 h), and simple operation, and therefore has a broad application prospect in clinical medicine., (© 2024. The Author(s).)

Introduction: There are a growing number of surgical approaches for laparoscopic radical resection of right-sided colon cancer, while there are relatively few comparative analyses of the different surgical approaches., Objective: To evaluate the safety and efficacy of different surgical approaches (intermediate approach, caudolateral approach, caudolateral combined with intermediate approach) for laparoscopic radical resection of right-sided colon cancer by conducting a network meta-analysis (NMA)., Method: We searched PubMed, Web of science and China National Knowledge Infrastructure (CNKI) databases. We reviewed the Chinese and English literature on controlled studies of laparoscopic radical resection of right-sided colon cancer including intermediate approach, caudolateral approach and caudolateral combined with intermediate approach, reported from the establishment of the database to September 2023. The inclusion and exclusion criteria were independently conducted by two researchers and relevant data was extracted from the qualifying literature and analyzed using Stata15 software., Results: Nine controlled studies of relevance including 715 patients were screened with right-sided colon cancer. Net meta-analysis showed that compared with the intermediate approach, the caudolateral approach was superior to the intermediate approach in terms of operation time (SMD = 0.75, 95% CI = 0.38 ~ 1.12, P = 0.0001), and bleeding volume (SMD = 1.15, 95% CI = 0.18 ~ 2.13, P = 0.002), while the difference was not statistically significant among the caudolateral approach compared with the intermediate approach in terms of the number of lymph node dissection, postoperative complication rate, time to first postoperative flatus and postoperative hospitalization. Compared with the intermediate approach, the combined approach was superior to the intermediate approach in terms of operation time (SMD = -0.87, 95% CI = -1.22 ~ -1.52, P < 0.05), bleeding volume (SMD = -1.09, 95% CI = -1.98 ~ -0.19, P < 0.05), the number of lymph node dissection (SMD = 0.21, 95% CI = 0.01 ~ 0.41, P < 0.05), and postoperative complication rate (RR = 2.24, 95% CI = 1.21 ~ 4.13, P < 0.05), while the difference was no statistically significant among the combined approach compared with the intermediate approach in terms of time to first postoperative flatus and postoperative hospitalization. Compared with the caudolateral approach, there was no statistically significant difference between the caudolateral approach and the combined approach in terms of operation time, bleeding volume, the number of lymph node dissection, postoperative complication rate, time to first postoperative flatus and postoperative hospitalization. According to the results of the surface under the cumulative ranking curve (SUCRA), the caudolateral approach and the combined approach were superior to the intermediate approach in terms of operation time (SUCRA: 65.1%, 84.9%, 0), bleeding volume (SUCRA: 77%, 71.9%, 1%), the number of lymph node dissection (SUCRA: 49.6%, 90.8%, 9.7%), postoperative complication rate (SUCRA: 46.6%, 97.5%, 5.9%), time to first postoperative flatus (SUCRA: 67%, 77.8%, 5.2%), postoperative hospitalization (SUCRA: 30.8%, 96.4%, 22.8%)., Conclusion: The caudolateral combined with intermediate approach and the caudolateral approach are safer and more effective than the intermediate approach. According to the results of SUCRA, the combined approach is superior to the caudolateral approach in terms of operation time, the number of lymph node dissection, postoperative complication rate, time to first postoperative flatus and postoperative hospitalization, the caudolateral approach is superior to the combined approach in term of bleeding volume., (© 2024. The Author(s).)

Background: The purpose of this study was to evaluate the repeatability and agreement of multispectral refraction topography (MRT) in measuring retinal refraction before and after cycloplegia in children. The results of this study will provide valuable insights into the accuracy and reliability of MRT as a tool for assessing retinal refraction in pediatric patients., Methods: Children aged 7 to 18 years old were recruited for this prospective research. The central and peripheral retinal refraction was measured three times using multispectral refraction topography (MRT) before and after cycloplegia. The retinal deviation value (RDV) was used to describe the average peripheral refractive error of the retina. In addition, objective refraction (OR) and subjective refraction (SR) measurements were also performed., Results: A total of 60 children with a mean age of 10.50 ± 1.81 years were enrolled. Before cycloplegia, all the central and peripheral retinal refraction parameters showed good repeatability with the lowest intraclass correlation coefficient (ICC) being 0.78 in the retinal deviation value from 45° eccentricity to 53° of the retina (RDV 45-53). After cycloplegia, the repeatability of MRT was significantly enhanced (lowest ICC = 0.91 in RDV-I). The 95% limits of agreement (LoA) of the central refraction and OR ranged from - 2.1 to 1.8 D before cycloplegia, and from - 1.69 to 0.27 D after cycloplegia. The 95% LoA of the central refraction and SR ranged from - 1.57 to 0.36 D after cycloplegia. All the 95% LoA demonstrated high agreement., Conclusions: The MRT shows high agreement with autorefractometry and experienced optometrist in measuring central refraction. Additionally, the MRT provides good repeatable measurements of retinal peripheral refraction before and after cycloplegia in schoolchildren., (© 2024. The Author(s).)

Background: Acute kidney injury (AKI) is a major complication following cardiac surgery with a high incidence in those with existing kidney dysfunction. Platelet distribution width (PDW) reflects variability in platelet size and serves as an indicator of platelet activation. Recent investigations linked PDW changes to kidney pathology, suggesting its utility in identifying individuals at risk for AKI, thus necessitating exploration of its predictive value., Methods: Patients with preoperative renal dysfunction [15 ≤ estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m 2 ] who underwent cardiac surgery from January 2018 to December 2021 were retrospectively enrolled. PDW values were measured preoperatively and again upon admission to the ICU immediately after cardiac surgery, with the change in PDW (dPDW) defined as the difference between these two measurements. The primary outcome was postoperative AKI, defined base on the Kidney Disease: Improving Global Outcomes (KDIGO) definition and staging criteria. Multivariate regression models were performed to identify the association between dPDW and AKI and its potential trend. Restricted cubic spline analysis assessed non-linear associations between dPDW and AKI. The Youden index identified an optimal dPDW cut-off for AKI prediction. Subgroup analysis was performed to elucidate the consistency of these associations across the various subgroups., Results: AKI occurred in 53.10% (513/966) of patients, accompanied by significant PDW increases in cases of AKI (P < 0.001). After adjusting confounders, dPDW was identified as a significant risk factor for AKI [odds ratio (OR) = 1.09, 95% confidence interval (CI): (1.02 ~ 1.16), P = 0.012]. Patients in the highest dPDW quartile (Q4) had a 195% higher AKI risk compared to those in the lowest quartile (Q1) (OR = 2.95, 95% CI:1.78 ∼ 4.90, P < 0.001). Trend analysis indicates that the risk of AKI increased with higher dPDW quartiles (P for trend < 0.001). Youden index showed that dRDW = 1.1 was identified as the optimal diagnostic cut-off value for AKI. Subgroup analyses and interaction tests showed a robust association between dPDW and AKI in all subgroups (P for interaction > 0.05)., Conclusions: This study underscored perioperative PDW changes as a significant predictor of postoperative AKI in patients with renal insufficiency, highlighting its potential in refining risk stratification and management strategies., Clinical Trial Number: Not applicable for this observational retrospective study., (© 2024. The Author(s).)

Specific intestinal metabolites are closely associated with the classification, severity, and necrosis of acute pancreatitis (AP) and provide novel insights for in-depth clinical investigations. In this study, the gut microbiota and metabolites of 49 AP patients at different treatment stages and severities were analysed via 16S rDNA sequencing and untargeted metabolomics to investigate the trends in gut microbiota composition and metabolome profiles observed in patients with severe AP. These findings revealed an imbalance in intestinal flora homeostasis among AP patients characterized by a decrease in probiotics and an increase in opportunistic pathogens, which leads to damage to the intestinal mucosal barrier through reduced short-chain fatty acid (SCFA) secretion and disruption of the intestinal epithelium. This dysbiosis influences energy metabolism, anti-inflammatory responses, and immune regulation, and these results highlight significant differences in energy metabolism pathways. These findings suggest that the differential composition of intestinal flora, along with alterations in intestinal metabolites and metabolic pathways, contribute to the compromised integrity of the intestinal mucosal barrier and disturbances in energy metabolism in patients with severe AP., (© 2024. The Author(s).)

Background: Numerous studies have indicated a growing prevalence of hyperuricemia. Elevated levels of serum uric acid (SUA) have been established as influential factors in conditions such as obesity, metabolic syndrome, diabetes mellitus, gout, and cardiovascular disease. Overweight and obesity are closely related to an increase in SUA. Our objective is to demonstrate the mediating role of liver enzyme in the correlation between body mass index (BMI) and SUA., Methods: A total of 5925 adults aged 18 to 65 were included in this cross-sectional study. Logistic regression and mediation analysis were used to investigate the relationship between BMI and hyperuricemia as well as liver enzyme levels. Standard methods were used to determine the biochemical indexes, including SUA, liver enzymes, and blood lipids in the collected samples., Results: The study revealed that the prevalence of hyperuricemia was 28.0%. Furthermore, the prevalence of overweight and obesity was as high as 48.5%, with 70.7% of this subgroup presenting with hyperuricemia. There was a positive correlation between BMI and hyperuricemia, and elevated levels of liver enzymes (ALT, AST, GGT) were associated with a higher risk of hyperuricemia. The study also observed a positive correlation between BMI and liver enzymes (ALT, AST, GGT). The study findings suggested that ALT, AST, and GGT played significant mediating roles in the relationship between BMI and SUA. Specifically, the unadjusted model revealed that ALT and GGT accounted for 22.12% and 18.13% of the mediation effects, respectively., Conclusions: The study found that BMI is associated with hyperuricemia, where liver enzyme abnormalities may have a mediating role. It is suggested that being overweight or obese may affect liver enzyme levels, leading to increased SUA levels. Controlling weight and liver enzyme levels may help prevent and treat hyperuricemia., (© 2024. The Author(s).)

Chronic pain dramatically affects life qualities of the sufferers. It has posed a heavy burden to both patients and the health care system. However, the current treatments for chronic pain are usually insufficient and cause many unwanted side effects. Chemokine C-X-C motif ligand 13 (CXCL13), formerly recognized as a B cell chemokine, binds with the cognate receptor CXCR5, a G-protein-coupled receptor (GPCR), to participate in immune cell recruitments and immune modulations. Recent studies further demonstrated that CXCL13-CXCR5 signaling is implicated in chronic pain via promoting neuroimmune interaction and neuroinflammation in the sensory system. In addition, some latest work also pointed out the involvement of CXCL13-CXCR5 in the pathogenesis of certain neurological diseases, including ischemic stroke and amyotrophic lateral sclerosis. Therefore, we aim to outline the recent findings in regard to the involvement of CXCL13-CXCR5 signaling in chronic pain as well as certain neurological diseases, with the focus on how this chemokine signaling contributes to the pathogenesis of these neurological diseases via regulating neuroimmune interaction and neuroinflammation. Strategies that can specifically target CXCL13-CXCR5 signaling in distinct locations may provide new therapeutic options for these neurological diseases., (© 2024. The Author(s).)

Asthma is a complex chronic respiratory inflammatory disease affected by both genetic and environmental factors. Therefore, our study explored the influence of TRIM11 on asthma and its underlying mechanisms. Our research involved patients diagnosed with asthma and healthy volunteers recruited from our hospital. We observed a reduction in serum TRIM11 expression in asthma patients, which positively correlated with the levels of anti-IgE or IgE. Additionally, both TRIM11 mRNA and protein expression in lung tissue were diminished. The introduction of the TRIM11 gene resulted in a reduction in inflammation in an in vitro asthma model and prevented the development of asthma in a mouse model. Moreover, the TRIM11 gene exhibited a suppressive effect on Ferroptosis and mitigated ROS-induced mitochondrial damage in the asthma model. TRIM11 was found to stimulate UBE2N-TAX1BP1 signaling in the asthma model, with UBE2N being identified as the specific target for TRIM11's effects on Ferroptosis. Furthermore, TRIM11 protein interacted with UBE2N protein and facilitated the dissociation of UBE2N-UBE2N in the asthma model. In conclusion, TRIM11 plays a vital role in preventing Ferroptosis in the asthma model through UBE2N-TAX1BP1 signaling. This indicates that targeting the TRIM11 mechanism could serve as a promising strategy for anti-Ferroptosis immunotherapy in asthma treatment., (© 2024. The Author(s).)

Background: Fertilization practices control bacterial wilt-causing Ralstonia solanacearum by shaping the soil microbiome. This microbiome is the start of food webs, in which nematodes act as major microbiome predators. However, the multitrophic links between nematodes and the performance of R. solanacearum and plant health, and how these links are affected by fertilization practices, remain unknown., Results: Here, we performed a field experiment under no-, chemical-, and bio-organic-fertilization regimes to investigate the potential role of nematodes in suppressing tomato bacterial wilt. We found that bio-organic fertilizers changed nematode community composition and increased abundances of bacterivorous nematodes (e.g., Protorhabditis spp.). We also observed that pathogen-antagonistic bacteria, such as Bacillus spp., positively correlated with abundances of bacterivorous nematodes. In subsequent laboratory and greenhouse experiments, we demonstrated that bacterivorous nematodes preferentially preyed on non-pathogen-antagonistic bacteria over Bacillus. These changes increased the performance of pathogen-antagonistic bacteria that subsequently suppressed R. solanacearum., Conclusions: Overall, bacterivorous nematodes can reduce the abundance of plant pathogens, which might provide a novel protection strategy to promote plant health. Video Abstract., (© 2024. The Author(s).)

Background: Buffalo is a globally important livestock species, but its reproductive performance is relatively low than cattles. At present, dominant follicle development specific process and mechanistic role of follicular growth related genes in water buffaloes are not well understood. Therefore, we comprehensively performed transcriptomics of granulosa cells and oocytes from different-sized follicles in water buffalo to identify key candidate genes that influence follicle development and diameter, and further explored the potential regulatory mechanisms of granulosa cells and oocytes in the process of water buffalo follicle development., Results: In this study, we found918 granulosa cell transcripts and 1401 oocyte transcripts were correlated in follicles of different diameters, and the expression differences were significant. Subsequent enrichment analysis of the co-expressed differentially expressed transcripts identified several genes targeted by long non-coding RNAs (lncRNAs) and associated with follicular development. Notably, the upregulation of BUB1 regulated by MSTRG.41325.4 and interactive action of SMAD2 and SMAD7 might have key regulatory role in follicular development. Additionally, we also detected key differentially expressed genes that potentially influence follicular hormone metabolism and growth, like ID2, CHRD, TGIF2 and MAD2L1, and constructed an interaction network between lncRNA transcripts and mRNAs., Conclusions: In summary, this study preliminarily revealed the differences in gene expression patterns among buffalo follicles of different sizes and their potential molecular regulatory mechanisms. It provides a new perspective for exploring the mechanism of buffalo follicular dominance and improving buffalo reproductive performance., (© 2024. The Author(s).)

Background: Postpartum hemorrhage is one of the leading causes of maternal mortality and morbidity. The etiology of postpartum hemorrhage exhibits variations in relation to the mode of birth; consequently, risk factors for massive transfusion in elective cesarean section might diverge from those encountered in vaginal birth or emergency cesarean section. The main purpose of this study was to investigate antepartum risk factors of massive transfusion for elective cesarean section., Methods: We conducted a retrospective cohort study based on data from a nationwide system that collected inpatient medical records from tertiary hospitals in mainland China. We included women who had undergone elective cesarean section from January 2013 to August 2018. Primary outcome was massive transfusion defined as transfusion of more than eight units of red blood cells on the day of childbirth. Candidate risk factors were identified by the 10th revision of International Classification of Diseases Codes of admission diagnoses. The relationship between each factor and massive transfusion was assessed using multivariable logistic regression., Results: A total of 294,695 women were included and 572 of them received massive transfusion (incidence: 194 per 100,000 elective cesarean sections). Maternal age [adjusted odds ratio (aOR) 1.22; 95% confidence interval (CI) 1.10-1.48], anemia (aOR 1.66; 95% CI 1.34-2.05), thrombocytopenia (aOR 3.54; 95% CI 2.39-5.05), coagulopathy (aOR 25.92; 95% CI 8.59-69.50), hypoalbuminemia (aOR 2.97; 95% CI 1.86-4.53), hepatic dysfunction (aOR 1.65; 95% CI 1.04-2.47), uterine scar (aOR 1.39; 95% CI 1.15-1.67), multiple pregnancy (aOR 2.84; 95% CI 1.74-4.38), polyhydramnios (aOR 2.52; 95% CI 1.19-4.68) and placenta previa (aOR 25.03; 95% CI 21.04-29.77) were associated with massive blood transfusion for elective cesarean section. Among the women receiving massive blood transfusion, 7 (1.2%) died during hospitalization, 126 (22.0%) needed hysterectomy, 25 (4.4%) uterine packing and 57 (10.0%) uterine artery ligation., Conclusions: Ten risk factors of massive transfusion were identified in women undergoing elective cesarean section. Our findings may facilitate blood products preparation and provide opportunities for applying prophylactic strategies prior to cesarean section for women at high risk of massive transfusion., (© 2024. The Author(s).)

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood., Methods: Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms., Results: Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86 + pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels., Conclusions: In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE., (© 2024. The Author(s).)

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy., (© 2024. The Author(s).)

Background: Working memory (WM), a core component of executive functions, relies on a dedicated brain system that maintains and stores information in the short term. While extensive neuroimaging research has identified a distributed set of neural substrates relevant to WM, their underlying molecular mechanisms remain enigmatic. This study investigated the neural correlates of WM as well as their underlying molecular mechanisms., Results: Our voxel-wise analyses of resting-state functional MRI data from 502 healthy young adults showed that better WM performance (higher accuracy and shorter reaction time of the 3-back task) was associated with lower functional connectivity density (FCD) in the left inferior temporal gyrus and higher FCD in the left anterior cingulate cortex. A combination of transcriptome-neuroimaging spatial correlation and the ensemble-based gene category enrichment analysis revealed that the identified neural correlates of WM were associated with expression of diverse gene categories involving important cortical components and their biological processes as well as sodium channels. Cross-region spatial correlation analyses demonstrated significant associations between the neural correlates of WM and a range of neurotransmitters including dopamine, glutamate, serotonin, and acetylcholine., Conclusions: These findings may help to shed light on the molecular mechanisms underlying the neural correlates of WM., (© 2024. The Author(s).)