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Recently, CAR-T cell therapy in hematological malignancies has received extensive attention. The objective of this study is to gain a comprehensive understanding of the current research status, development trends, research hotspots, and emerging topics pertaining to CAR-T cells in the treatment of hematological malignancies. Articles pertaining to CAR-T cell therapy for hematological malignancies from the years 2012 to 2023 were obtained and assessed from the Web of Science Core Collection (WoSCC). A bibliometric approach was employed to conduct a scientific, comprehensive, and objective quantitative analysis, as well as a visual analysis, of this particular research domain. A comprehensive analysis was conducted on a corpus of 3643 articles, which were collaboratively authored by 72 countries and various research institutions. CAR-T cell research in treating hematological malignancies shows an increasing trend each year. Notably, the study identified the countries and institutions displaying the highest level of activity, the journals with the most citations and output, as well as the authors who garnered the highest frequency of citations and co-citations. Furthermore, the analysis successfully identified the research hotspots and highlighted six emerging topics within this domain. This study conducted a comprehensive exploration and analysis of the research status, development trends, research hotspots, and emerging topics about CAR-T cells in the treatment of hematological malignancies from 2012 to 2023. The findings of this study will serve as a valuable reference and guide for researchers seeking to delve deeper into this field and determine the future direction of their research.

Myocardial ischemia-reperfusion injury (MIRI) is a complex pathological process that results from the restoration of blood flow to ischemic myocardium, leading to a series of detrimental effects including oxidative stress and inflammation. Stachyose, a naturally occurring oligosaccharide found in traditional Chinese medicinal herbs, has been suggested to possess therapeutic properties against various pathological conditions. However, its impact on MIRI and the underlying mechanisms have not been fully elucidated. In this study, we aimed to investigate the therapeutic effects of stachyose on MIRI and to uncover the molecular mechanisms involved. Using both in vivo and in vitro models of MIRI, we evaluated the effects of stachyose on cardiac function and cell death pathways. Our results indicate that stachyose significantly improves cardiac function and reduces infarct size in MIRI mice. Mechanistically, stachyose modulates the ferroptotic pathway in cardiomyocytes by upregulating the expression of glutathione peroxidase 4 (GPX4) and reducing lipid peroxides and iron levels. Additionally, stachyose inhibits the pyroptotic pathway in macrophages by downregulating the expression of NLRP3, gasdermin D (GSMD-N), and cleaved-caspase-1, leading to decreased levels of proinflammatory cytokines interleukin (IL)-1β and IL-18. This study demonstrates that stachyose exerts a protective effect against MIRI by targeting both ferroptosis and pyroptosis pathways, suggesting its potential as a novel therapeutic agent for the treatment of MIRI. Further research is warranted to explore the detailed mechanisms and therapeutic potential of stachyose in clinical settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Programmed death protein 1 (PD-1) inhibitors have potent anti-tumor activities. However, they often result in immune-related adverse events (irAEs) of varying severity. Therefore, the factors affecting the incidence of irAEs warrant urgent investigation. This study aimed to identify specific and sensitive predictors of irAEs in a Chinese population. We conducted a genome-wide association study (GWAS) comprising 80 patients with malignant tumors to evaluate single-nucleotide polymorphism (SNP) loci associated with the incidence of irAEs. The SNP rs2157775 on the LOC339166 gene had the lowest P value but did not reach the significance threshold after Bonferroni correction. Therefore, potentially associated SNPs were further investigated through the mechanism-related PD-1 pathway using the ImmPort and PathCards Human Gene Databases. A binary logistic regression model revealed that CD3E (rs3782040) A/A was associated with a lower incidence of irAEs in patients with malignant tumors who received PD-1 inhibitors. In contrast, PTPN11 (rs143894582) C/CA was associated with a higher incidence of irAEs. These findings provide a basis for the verification and identification of new loci to provide insight into the etiology of irAEs., (Copyright © 2024. Published by Elsevier B.V.)

Influenza A virus (IAV) leads to significant morbidity and mortality due to the seasonal epidemics and spread. We have demonstrated that oleanolic acid (OA) C28 glucose conjugates and OA trimers are capable of effectively blocking the recognition and interaction between the influenza virus and host cells. In this study, a series of OA-glucose trimers were designed and synthesized through the CuAAC reaction. All trimers underwent screening for anti-IAV activities in vitro. Among these, compounds 13a and 13b showed inhibitory activity against the influenza virus, with IC 50 values of 0.68 μM and 0.47 μM, respectively, demonstrating greater potency than oseltamivir (IC 50  = 1.36 μM). Results from the time-of-addition experiment and hemagglutination inhibition assay suggest that these OA-glucose trimers may disrupt the recognition between the HA protein of IAV and sialic acid receptors on host cells, thus blocking viral entry. Furthermore, it was found that compound 13b effectively inhibits IAV infection in BALB/c mice. This study has elucidated the structure-activity relationships of OA trimers against the influenza virus and highlighted the utility of multivalent OA conjugates for enhancing ligand-target interactions in anti-influenza virus drug design, laying a groundwork for future research into the antiviral applications of these natural products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Methamphetamine (METH) is the second abused drug which affects abusers' health and induces social crimes, developing novel methods with high sensitivity and selectivity for METH detecting is still challenging. In this paper, a colorimetric and fluorescent dual-channel sensor for METH has been constructed. We combine the enzyme-mimic catalytic activity of gold nanoparticles (GNPs) with high target specificity of METH aptamer to create a nanosensor (Apt-GNP), in the presence of METH, the absorption of 3,3',5,5'-tetramethylbenzidine (OxTMB) at 650 nm enhanced with METH concentration increasing, while the absorption characteristic peak of GNPs at 530 nm remained almost unchanged. The ratio of A 650nm /A 530nm and METH concentration had a good linear relationship when METH concentration was in the range of 5-50 μM, and the corresponding linear equation is A 650nm /A 530nm  = 0.00727C METH (μM) + 0.783 with R 2  = 0.997 and LOD = 0.40 μM (LOD = 3σ/s, n = 11). Interestingly, the fluorescence emission of Rhodamine B (RB) overlaps with the absorption spectrum of OxTMB which represents the content of METH and the fluorescence signal of RB can be quenched through internal filtering effect (IEF). Hence, when RB was doped to the detection system, the decay of RB fluorescence can reflect the concentrations change of METH. Accordingly, the linear equation is F/F R  = -0.00751C METH (μM) + 0.895 with R 2  = 0.993 and LOD = 0.40 μM, where F was the fluorescence of the analytical solution at 580 nm with METH and F R was fluorescence of RB control solution. The dual-channel sensor can measure METH in serum and artificial urine successfully which is potential to be applied in drug-using crime sites and provide direct evidence to law enforcement officials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine-mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet-monocyte aggregates (MPAs) are mediated by an initial interaction of P-selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL-1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte-activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14 + CD16 - ) into proinflammatory monocytes (CD14 + CD16 + ). The platelet-activated monocytes release interleukin-1 and tissue necrotic factor-α, which promote further platelet activation. KD-induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14 + CD16 +  monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet-monocyte interactive proteins (CD62p/PSGL-1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Treating methicillin-resistant Staphylococcus aureus (MRSA) infection remains one of the most difficult challenges in clinical practice, primarily due to the resistance of MRSA to multiple antibiotics. Therefore, there is an urgent need to develop novel antibiotics with high efficacy and low cross-resistance rates. In this study, a series of novel pleuromutilin derivatives with coumarin structures were synthesized and subsequently assessed for their biological activities. Most of these derivatives showed potent antimicrobial activity against drug-resistant Gram-positive bacterial strains. Compound 14b displayed particularly rapid bactericidal effects, slow resistance development, and low cytotoxicity. Moreover, it decreased bacterial loads in the lung, liver, kidney, spleen, and heart and exhibited better antibacterial efficacy (ED 50 = 11.16 mg/kg) than tiamulin (ED 50 = 28.93 mg/kg) in a mouse model of systemic MRSA infection. Both in vitro and in vivo analyses suggest that compound 14b is a promising agent for the treatment of MRSA infections.

Photoelectrochemical photodetectors (PEC PDs) are promising in underwater optoelectronic devices because of their low cost, good sensitivity, and self-powered characteristics. However, achieving high-performance omnidirectional visible PEC PDs using seawater as the electrolyte is still challenging, hindering their practical application. This work successfully synthesized CuO nanobelt arrays (NAs) on a linear copper wire via a low-temperature solution method with an annealing process. The self-powered CuO NA PEC PDs exhibit good UV-vis-NIR photoresponse ranging from 365 to 850 nm with a high responsivity of -83.18 mA/W (455 nm irradiation), a fast response time of 28/140 ms, and good stability in simulated seawater. The high responsivity surpasses all of the reported PEC PDs when seawater or simulated seawater is used as the electrolyte. In addition, the CuO NA PEC PDs show good 360° omnidirectional photodetection and underwater wireless optical communication capabilities. This work provides new insights into achieving omnidirectional visible PEC PDs and demonstrates the potential application of CuO NAs in underwater optoelectronic devices.

The subjectivity of morphological assessment and the overlapping pathological features of different subtypes of myeloproliferative neoplasms (MPNs) make accurate diagnosis challenging. To improve the pathological assessment of MPNs, we developed a diagnosis model (fusion model) based on the combination of bone marrow whole-slide images (deep learning [DL] model) and clinical parameters (clinical model). Thousand and fifty-one MPN and non-MPN patients were divided into the training, internal testing and one internal and two external validation cohorts (the combined validation cohort). In the combined validation cohort, fusion model achieved higher areas under curve (AUCs) than clinical or DL model or both for MPNs and subtype identification. Compared with haematopathologists with different experience, clinical model achieved AUC which was comparable to seniors and higher than juniors (p = 0.0208) for polycythaemia vera. The AUCs of fusion model were comparable to seniors and higher than juniors for essential thrombocytosis (p = 0.0141), prefibrotic primary myelofibrosis (p = 0.0085) and overt primary myelofibrosis (p = 0.0330) identification. In conclusion, the performances of our proposed models are equivalent to senior haematopathologists and better than juniors, providing a new perspective on the utilization of DL algorithms in MPN morphological assessment., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

T cells within the tumor microenvironment frequently exhibit dysfunctional characteristics that compromise their ability to elicit both innate and therapeutic-induced immune responses. Regulators of immune dysfunction represent therapeutic targets to activate anti-tumor immunity. In this study, we identified semaphorin 3G (SEMA3G) as a key regulator of immune responses in cancer. SEMA3G was widely upregulated in diverse human cancers, and its expression was positively correlated with tumor progression. SEMA3G acted as a ligand that inhibited the activation and functionality of T cells. A comprehensive receptor screening approach demonstrated that SEMA3G exhibited a significantly stronger affinity for neuropilin NRP1 compared to NRP2. Furthermore, SEMA3G primarily impeded T-cell functions via NRP1. Disruption of SEMA3G using CRISPR/Cas9 technology or blockade with a neutralizing antibody effectively restored the cytotoxicity of CD8+ T cells and inhibited the growth of tumors in vivo. This research underscores the role of SEMA3G in T-cell dysfunction within tumors and proposes a targeting SEMA3G as a cancer immunotherapeutic strategy.

Background: Subarachnoid hemorrhage (SAH) is a severe neurological event with high mortality. The choice of sedatives in SAH management may influence patient outcomes. This study aimed to investigate the association between sedatives and in-hospital mortality among SAH patients., Methods: This study analyzed data from the MIMIC-IV database, and in-hospital mortality was the primary outcome. Key variables collected included sedatives, demographics, comorbidities, vital signs, laboratory tests, and severity scores. Univariate and multivariate logistic regression analyses were used to assess associations between sedative use and in-hospital mortality, with adjustments for confounding factors. Further stratified analyses explored the effects of dexmedetomidine across different patient subgroups, and mediation analysis evaluated creatinine's role in the relationship between dexmedetomidine and mortality., Results: A total of 527 patients were included in this study, with 301 males. Compared to propofol and midazolam, the use of dexmedetomidine was significantly related to the reduction of in-hospital mortality in SAH patients (OR = 0.369, 95% CI: 0.237-0.574, p < 0.001). After adjusting for variables such as demographics, comorbidities, and laboratory tests, dexmedetomidine remained associated with lower in-hospital mortality. Additionally, our findings indicated that dexmedetomidine use was associated with a reduced risk of in-hospital mortality regardless of the presence of cerebrovascular disease. Importantly, we discovered that creatinine acted as a mediator in the protective effect of dexmedetomidine on in-hospital mortality., Conclusion: Dexmedetomidine is associated with significantly lower in-hospital mortality in SAH patients. These findings underscore the importance of sedative choice for SAH patients, suggesting that dexmedetomidine could enhance patient outcomes., (Copyright © 2024. Published by Elsevier Inc.)

RNA-based vaccines against SARS-CoV-2 have demonstrated promising protective immunity against the global COVID-19 epidemic. Enhancing the intensity and duration of mRNA antigen expression is anticipated to markedly boost antiviral immune responses. Self-amplifying RNA (saRNA) represents a next-generation platform for RNA-based vaccines, amplifying transcripts in situ to augment the expression of encoded immunogens. Here, we develop a saRNA nanovaccine, formulated with a mutated saRNA encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike glycoprotein, encapsulated within a lipid nanoparticle (LNP-saRNA-RBD). This LNP-saRNA vaccine platform enables efficient delivery of saRNA-RBD, inducing enhanced and prolonged expression of the RBD antigen. LNP-saRNA-RBD vaccination stimulated the generation of antigen-specific T cells, promoting their differentiation into a long-lived effector memory phenotype. Immunization with LNP-saRNA-RBD induced a germinal center response in draining lymph nodes, leading to the production of anti-RBD IgG antibodies with the ability to neutralize SARS-CoV-2 pseudovirus. Furthermore, prime-boost immunizations with LNP-saRNA-RBD conferred protection to mice against SARS-CoV-2 challenge by suppressing viral infection and replication, as well as pulmonary inflammatory responses and associated damage. Taken together, these findings provide strong support for advancing the development of LNP-saRNA-RBD as a safe and efficacious vaccine candidate against SARS-CoV-2 infection., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: The present study assessed the correlation between anxiety and depression in young and middle-aged Chinese patients with coronary artery disease (CAD)., Patients and Methods: This study included 313 patients diagnosed with premature CAD at the Department of Cardiology between January and July 2023. The Zung Self-Rating Anxiety/Depression Scale (SAS/SDS) was used as a standardized scale to assess mental health symptoms. A binary logistic regression model (backward) was used to analyze the correlation between anxiety and depression in premature CAD., Results: Anxiety was observed in 154 persons with a prevalence of 49.20%, with a median SAS score of 53.0 (52.00-54.00). Depression was observed in 91 patients, with a prevalence of 29.07%, with a median SDS score was 55.00 (54.00-57.00). A total of 63 (20.13%) patients had comorbid anxiety and depression. Multivariate logistic regression analysis revealed that anxiety was positively associated with severe coronary artery stenosis, systolic blood pressure (SBP), body mass index, and snoring. However, it is negatively associated with high-income levels. Depression was positively associated with age, severe coronary artery stenosis, and snoring. However, it was negatively associated with SBP. Comorbid anxiety and depression were positively associated with age, severe coronary artery stenosis, and snoring., Conclusion: For the first time, we investigated the prevalence and correlators of anxiety and depression in premature CAD. Therefore, the correlators of emotional status should be routinely evaluated in both primary and specialized care services., Competing Interests: The author(s) report no conflicts of interest in this work., (© 2024 Li et al.)

Objective: This study aimed to examine the levels of solute carrier family seven number 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the serum of patients with acute ischaemic stroke (AIS) and their relationship with disease severity., Methods: A total of 148 patients with AIS together with 148 healthy controls (HCs) were enrolled. The expression levels of SLC7A11 and GPX4 in serum were detected immediately as early as possible. Radiographic severity was detected by Alberta Stroke Program Early CT Score (ASPECTS). Disease severity was evaluated using modified Rankin Scale (mRS). High-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) expression levels were also measured. A correlation analysis was conducted to determine the relationship between the expression levels of SLC7A11 and GPX4 with the clinical severity of the disease and the levels of hs-CRP and MMP-9. Furthermore, receiver operating characteristic (ROC) curve analysis was utilized to assess the potential of SLC7A11 and GPX4 as diagnostic markers., Results: Compared to the HC group, the serum expression levels of SLC7A11 and GPX4 were significantly lower in the AIS group. Serum SLC7A11 levels were positively associated with serum GPX4 levels. The AIS group included 50 patients with mild neurological impairment, 52 with moderate neurological impairment, and 46 with severe neurological impairment. AIS patients with mild neurological impairment had drastically higher serum SLC7A11 and GPX4 levels compared with those with moderate neurological impairment. AIS patients with moderate neurological impairment showed significantly higher serum SLC7A11 and GPX4 concentrations compared with those with severe neurological impairment. ROC curve analysis demonstrated that both serum SLC7A11 and GPX4 may both act as potential indicators for evaluating of AIS disease severity. In addition, both serum SLC7A11 and GPX4 levels were positively correlated with ASPECTS. Both serum SLC7A11 and GPX4 levels were negatively associated with hs-CRP as well as MMP-9 levels. Serum SLC7A11 and GPX4 levels were significantly increased following comprehensive therapy., Conclusions: Decreased SLC7A11 and GPX4 levels may reflect disease severity of AIS., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Nasopharyngeal carcinoma (NPC), historically termed 'lymphoepithelioma-like carcinoma' due to its rich lymphocyte infiltration, benefit from PD-1 blockade treatment. However, a comprehensive understanding of its tumor microenvironment (TME) remains elusive, hindering the identification of effective biomarkers for immunotherapy. We leveraged multimodal profiling data, including gene expression, immunohistochemistry, and multiplex immunohistochemistry, from three independent cohorts of NPC patients with a total of 327 patients to dissect the TME in NPC. Unsupervised hierarchical clustering of TME cell populations in the discovery cohort revealed two novel subtypes with distinct prognosis: 'Immune Inflamed' and 'Immune Deficient'. Intriguingly, the most significant differences between the two subtypes were the abundance of B cells and tertiary lymphoid structures (TLS), with a nearly two-fold increase in TLS presence in the Immune Inflamed subtype. The prognostic significance of TLS was confirmed in three independent NPC cohorts, surpassing the prognostic value of individual immune cell subsets. Mechanistically, TLS enhanced anti-tumor immunity by increasing T and B cell receptor repertoire diversity, promoting infiltration of plasma cells, macrophages, and natural killer cells, and consequently increasing antibody-dependent cell-mediated cytotoxicity and antibody-dependent phagocytosis. Finally, TLS status robustly predicted prognosis in a cohort of NPC patients treated with PD-1 blockade, and its prognostic value was consistent across a pan-cancer immunotherapy cohort of 10 tumors and 1158 patients, although with context-specific effects depending on cancer type and immunotherapy modality. In conclusion, this study provides compelling evidence that TLS is a robust indicator of overall immune response within TME and have great potential to guide individualized immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Most of the previous studies on costs following trauma have focused solely on in-hospital costs and costs associated with the acute treatment and early rehabilitation. As a result, post-hospital costs are often neglected in the estimation of total costs. We aimed to describe service utilization and total costs for health care services, rehabilitation services, and social support in the periods 0-6 months and 7-12 months after moderate-to-severe traumatic injury. Further, we explored costs and their associations with sociodemographic, clinical and injury-related variables., Methods: Data were obtained from a prospective, 12 months follow-up study of patients in all ages with moderate-to-severe traumatic injury determined by a New Injury Severity Score (NISS) > 9, admitted directly or within 72 h to the trauma referral centres in year 2020. Data on utilization of health care and rehabilitation services from the Norwegian Patient Register (NPR), the Municipal patient and user register (KPR), and the Norwegian Control and Payment of Health Reimbursements Database (KUHR) were used., Results: A total of 601 patients were included, 24% with moderate and 76% with severe injuries. The overall mean total health care cost per patient in the first year after traumatic injury was 846,877 (SD 1,042,649) Norwegian Kroner (NOK). The mean total cost of rehabilitation per patient was 251,487 (SD 317,050) NOK. Most costs were attributable to secondary care in the first six months post-injury. Severely injured patients had a higher health care utilization and average cost compared to those with moderate injury. Injury severity factors were the most prominent cost drivers, and number of injuries, severe head, spine, and extremity injuries were significantly associated with higher costs during the first year following trauma., Conclusions: The findings give a holistic insight into health care utilization and costs for patients across all ages with complex needs following trauma and can contribute to the planning and provision of services for this patient group., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Regional Committee for Medical and Health Research Ethics (Approval No. 31676) and the Institutional Data Protection Officers at OUH and UNN (Approval No. 19/26515 and 02423). Written, informed consent to participate were obtained from all participants. Parents gave their consent for children below the age of 18 years, and adolescents aged 16–17 years gave an additional informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The field of photoelectrochemical-type (PEC) ultraviolet (UV) photodetectors has witnessed swift progression due to their facile fabrication processes and self-powered function. The realization of high-performance and self-powered PEC UV photodetectors is attractive and challenging. In this study, the application of ZnAl mixed metal oxide (MMO) heterojunctions in self-powered PEC UV photodetectors is introduced for the first time. The MMO heterojunctions are composed of ZnO and ZnAl 2 O 4 , which provide a suitable band structure for accelerating the photogenerated carrier separation and transport, boosting UV photodetection. Irradiation of the self-powered MMO PEC UV photodetectors with UV light (365 nm) results in a high responsivity of 46.82 mA W -1 and a fast response time of 18/35 ms. An impressive UV/visible rejection ratio of 1088.8 and excellent multi-cycle stability are demonstrated, exceeding the most recently reported PEC UV photodetectors. Moreover, the MMO PEC UV photodetectors possess underwater optical communication capability, confirming promising potential for underwater optoelectronic devices. This study provides a new perspective on the development of high-performance PEC UV photodetectors., (© 2024 Wiley‐VCH GmbH.)

Endometriosis, affecting about 10% of individuals assigned female at birth, is challenging to diagnose and manage. Diagnosis typically involves the identification of various signs of the disease using either laparoscopic surgery or the analysis of T1/T2 MRI images, with the latter being quicker and cheaper but less accurate. A key diagnostic sign of endometriosis is the obliteration of the Pouch of Douglas (POD). However, even experienced clinicians struggle with accurately classifying POD obliteration from MRI images, which complicates the training of reliable AI models. In this paper, we introduce the Human-AI Collaborative Multi-modal Multi-rater Learning (HAICOMM) methodology to address the challenge above. HAICOMM is the first method that explores three important aspects of this problem: 1) multi-rater learning to extract a cleaner label from the multiple "noisy" labels available per training sample; 2) multi-modal learning to leverage the presence of T1/T2 MRI images for training and testing; and 3) human-AI collaboration to build a system that leverages the predictions from clinicians and the AI model to provide more accurate classification than standalone clinicians and AI models. Presenting results on the multi-rater T1/T2 MRI endometriosis dataset that we collected to validate our methodology, the proposed HAICOMM model outperforms an ensemble of clinicians, noisy-label learning models, and multi-rater learning methods., (© 2024 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: China has the highest number of people with dementia globally, and the responsibility of caring for people with dementia primarily falls on relatives, who bear heavy caregiving burdens and pressure. Providing care for an individual with dementia is emotionally and physically demanding, particularly due to the frequent manifestation of behavioral and psychological symptoms associated with dementia (BPSD). This underscores the crucial need to comprehend and address caregivers' emotional expression (EE)., Aim: To explore the characteristics of relatives with high expressed emotion of people with dementia and related factors in mainland China., Methods: A survey using cross-sectional questionnaires conducted with 165 relatives of individuals with dementia in China., Results: A significant number of relatives had high EE (n = 61, 39%). The variation in EE, about 37.8%, is explained by seven independent variables. The proportion of psychological distress among relatives in EE variation is 14.5%. (b = 0.387, p < 0.001). Length of care-taking, active coping, and chronic diseases accounted for 6.5% (b = 0.264, p < 0.001), 5.1% (b=-0.239, p = 0.001) and 4.1% (b = 0.211, p = 0.002) of the variance in EE, respectively., Conclusions: Chinese health care providers can identify high-risk groups for assistance based on the severity of dementia, age, health status and duration of care. Enhancing coping styles and alleviating emotional distress among relatives could be advantageous in decreasing EE., Clinical Evidence: Understanding the risk factors for high EE in different cultures can help guide practice on a global scale to improve the quality of life of people with dementia., Competing Interests: Declarations. Ethics approval and consent to participate: All participants signed an informed consent form prior to the start of the study. An introductory statement about the purpose of the study, the number of questions and the time needed to complete the survey was provided. They were informed that they could voluntarily withdraw from the study at any time without any negative consequences. The study was based on the principles of the Declaration of Helsinki and was approved by the Research Ethics Review Board of Jilin University (2022110305). Consent for publication: Not applicable. Human ethics and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Soundscape appropriateness (SA) provides supplemental information on the matching degree between auditory information and the surrounding scene in soundscape perception. This indicator has been integrated into the standard ISO process for collecting soundscape data, forming a component of the sound quality assessment questionnaire. However, its role in soundscape quality assessment has not been fully understood. Herein, we present the findings from soundscape data collected from Beiling Park in Shenyang, China. A method was developed that integrates mediation effect models with multiscale geographically weighted regression models to explore the mediating role of SA in the impact of sound source types on soundscape quality, as well as the spatial heterogeneity of this mediation effect. The results confirm that SA does mediates the influence of sound source types on acoustics comfort (AC). Specifically, natural sounds (indirect effect/total effect = .19/.19), traffic sounds (indirect effect/total effect = -.46/-.65), and commercial sounds (indirect effect/total effect = -.25/-.12) impact the perception of AC by either enhancing or reducing SA. Moreover, the relationships among variables depicted in this model demonstrate spatial heterogeneity, demonstrating that in urban open spaces with complex constructures, local spatial models may be needed for soundscape assessment. The research reaffirms the significance of SA in urban open spaces. In terms of practical implications for urban and landscape planners, when sound sources cannot be controlled or altered, coordinating between the sound and the surrounding environment through landscape optimisation could also improve the quality of the soundscape through enhancing SA and help achieve the goal of creating healthy urban open spaces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Relapse was the major cause of treatment failure in patients with myeloid malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring. The most used first-line regimens for MRD are immunotherapies. However, for patients who were ineligible for or failed in first-line immunotherapies, options were limited., Methods: A total of 20 patients with myeloid malignancies with recurrent MRD after allo-HSCT were included in this study. The safety and efficacy of venetoclax-based regimens were analyzed., Results: There were 13 patients (65%) treated with venetoclax combined with hypomethylating agents concomitantly and seven patients (35%) treated with venetoclax monotherapy. After venetoclax-based regimens, MRD was eliminated in 11 patients (55%) with 6 subsequently developing recurrent MRD and 5 remaining in molecular remission. MRD declined in two patients (10%), and no responses in seven patients (35%). Among the two patients with declined MRD, one patient finally eliminated MRD after two cycles of the venetoclax-based regimen, and the other patient's MRD further declined after the second regimen. The objective response rate (ORR) was 65%. The median duration of response was 103 (12-313) days. The incidences of grades 3-4 neutropenia, anemia, and thrombocytopenia independently of pretreatment status were 30%, 20% and 20%, respectively., Conclusion: Venetoclax-based regimens are efficient and safe for MRD in patients with myeloid malignancies ineligible for or failed in the first-line immunotherapies after allo-HSCT.

The toxic effects of ammonia exposure on Litopenaeus vannamei have been widely reported, including tissue damage, oxidative stress, and metabolic disorders, but the ability of L. vannamei to recover from ammonia damage is still unclear. To further understand the adaptation mechanism of L. vannamei to ammonia, this study explored the effects of ammonia exposure and recovery on histopathology, physiological indicators, and transcriptomic responses. In the ammonia exposure (NH 4 + -N 25 mg/L) and recovery experiment, shrimp were sampled at 0 h, 24 h, 48 h of exposure, and 24 h, 48 h of recovery. The results showed that histopathological damage to the hepatopancreas and gills caused by short-term ammonia exposure could be alleviated after recovery. Ammonia exposure inhibited superoxide dismutase (SOD) and catalase (CAT) activities, decreased total antioxidant capacity (T-AOC), and increased malondialdehyde (MDA) in shrimp. Restoration of the antioxidant system after exposure mitigated oxidative damage and reduced MDA levels. The inhibition of acid phosphatase (ACP) and alkaline phosphatase (AKP) activities in shrimp caused by ammonia exposure was reversible. Ammonia excretion and metabolism attenuate ammonia toxicity and promote recovery in L. vannamei. Transcriptome analysis identified 1690, 1568, and 1463 differentially expressed genes (DEGs) in the hepatopancreas at 48 h of stress, 24 h, and 48 h of recovery, respectively. KEGG enrichment analysis revealed that ammonia exposure induced oxidative damage, resulting in apoptosis. Furthermore, activation of antioxidant-related pathways, such as glutathione metabolism and peroxisomes, helped reduce oxidative damage during the post-exposure recovery period. The addition of exogenous spermine and spermidine may contribute to post-exposure recovery and enhance ammonia acclimation in L. vannamei. Differential expression of the inflammatory gene STEAP4 in the ammonia stress and recovery phases, as screened by transcriptome analysis, may play a positive role in post-stress recovery. This study demonstrated the reversibility of the toxic effects of ammonia exposure on L. vannamei, complemented the knowledge of the mechanisms of adaptation of shrimp under ammonia exposure, and provided a basis for subsequent ammonia tolerance studies in crustaceans., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jianyong Liu reports was provided by Zhanjiang City Guoxing Aquatic Technology Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Glioblastoma (GBM) is a cancer with high malignancy because of its rapid proliferation and high metastatic ability. LPCAT1 is reported to play a tumor-promoting role in multiple cancers, but its precise molecular mechanism in GBM remains to be further explored. We aim to explore the biological role of LPCAT1 in GBM. In this study, the expression of LPCAT1 and its correlation with clinicopathological characteristics of GBM patients were analyzed based on The Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier approach was adopted for plotting survival curves for patients showing different expression levels of LPCAT1. Meanwhile, LPCAT1 expression within 50 GBM tumor tissues and 30 non-tumor clinical samples was analyzed by qRT-PCR and western blot assays, respectively. Later, LPCAT1's effect on GBM tumorigenesis was analyzed in vivo and in vitro by CCK8, EdU proliferation, clone forming, scratch, TUNEL assays, and subcutaneous xenograft experiments. As a result, LPCAT1 expression elevated within GBM tumor tissues and cells. Overexpression of LPCAT1 enhanced GBM cell growth, invasion and migration, while accelerating cell cycle progression. LPCAT1 silencing significantly inhibited cell motility and proliferation in vivo and in vitro, and arrested U251 cells at G0/G1 phase. Moreover, LPCAT1 might play a role in GBM progression by activating the p-AKT-MYC signaling pathway. LPCAT1 activated AKT, which were synchronously up-regulated MYC to accelerate cancer progression. Knockdown of LPCAT1 induced the opposite changes to repress the viability and motility of GBM cells. LPCAT1 contributed to the progression of GBM by participating in the p-AKT-MYC axis., Competing Interests: Conflict of interestThe Authors declare that they have no conflict of interest to disclose., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Homeostatic dysregulation (HD), the measure of aging-related physiological dysregulation, serves as an essential intervenable indicator of aging., Objective: To explore the associations of three healthy dietary patterns with HD, investigate the most recommended dietary patterns, and identify the significant beneficial and harmful food groups METHODS: This prospective cohort study included 8,288 participants aged 30-79 years from the China Multi-Ethnic Cohort (CMEC), with a female majority (61.6%). Dietary information was obtained through the baseline food frequency questionnaire (FFQ). Three dietary patterns were constructed: Dietary Approaches to Stop Hypertension (DASH), alternative Mediterranean diets (aMED), and Healthy Diet Score (HDS). HD was constructed based on clinical biomarkers and anthropometric measurements. Follow-up analyses adjusted for baseline data were employed to assess the longitudinal associations of three dietary patterns at baseline with HD at follow-up. Additionally, quantile G-computation was utilized to evaluate the relative contribution of each food group to the association with HD., Results: Over a follow-up period of 2.0 years, all healthy dietary patterns exhibited negative associations with HD, with β Q5/Q1 = -0.112, 95%CI (-0.172, -0.051) for HDS, with β Q5/Q1 = -0.073, 95%CI (-0.134, -0.012) for aMED, with β Q5/Q1 = -0.047, 95%CI (-0.107,0.014) for DASH. The results of the component analyses revealed that soybean products were the most significant beneficial food group (relative contribution of 24.0%), while alcohol was identified as the major harmful food group (relative contribution of 76.9%)., Conclusion: Healthy dietary patterns, especially HDS, are negatively associated with HD. Additionally, soybean products and alcohol are the most significant beneficial and detrimental food groups respectively. Developing appropriate nutritional strategies may help reduce the burden of disease and promote healthy aging., Competing Interests: Conflict of interests All authors declare no competing interests., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background and Purpose: Metastasis of non-metastatic non-small cell lung cancer (NMNSCLC) to contralateral hilar lymph nodes (CHLN) eliminates the opportunity for radical therapy. This study aims to analyze whether CHLN metastasis in NMNSCLC is commonly overestimated in clinical practice and to establish a predictive model for enhanced precision., Methods and Materials: We conducted a retrospective analysis of 834 pathologically confirmed NMNSCLC patients. Monitoring of treatment responses and regular ≥ 1 year CT follow-up was used to determine the nature of CHLN. Lasso regression was used to select predictive factors, and a multivariate binary logistic regression model (HAM) was constructed. Internal validation was performed using ten-fold cross-validation., Results: The CHLN metastasis rate was 4.4% among the NMNSCLC patients. The positive predictive value (PPV) and sensitivity for PET-CT diagnosis were 36.8% and 67.5%, while for CT they are 44.8% and 70.2%, respectively. The five optimal predictive factors (emphysema or bullae, central-type lung cancer, short diameter of CHLN, calcification and SUVmax) were used to develop the HAM model. The Area under curve (AUC) values for PET-CT, CT, and HAM model were 0.81, 0.83, and 0.96, respectively. The F1 scores for PET-CT and CT were 0.48 and 0.55, respectively, while the maximum F1 score of our model was 0.73, with corresponding PPV and sensitivity of 66.7%, and 81.1%, respectively., Conclusions: CHLN metastasis is rare in NMNSCLC patients. PET-CT diagnosis significantly overestimates CHLN metastasis and the HAM model improves clinical decision-making in this study. Prospective studies are needed to confirm these conclusions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The focused assessment with sonography in trauma (FAST) examination plays an essential role in diagnosing hemoperitoneum in trauma patients to guide prompt operative management. The FAST examination is highly specific for hemoperitoneum in trauma patients, and has been adopted in nontrauma patients to identify intraperitoneal fluid as a cause of abdominal pain or distension. However, causes of false positive FAST examinations have been described and require prompt recognition to avoid diagnostic uncertainty and inappropriate procedures. Most causes of false positive FAST examinations are due to anatomic mimics such as perinephric fat or seminal vesicles, however, modern ultrasound machines use a variety of postprocessing image enhancement techniques that can also lead to novel false positive artifacts., Case Report: We report cases where experienced clinicians incorrectly interpreted ultrasound findings caused by a novel mimic of hemoperitoneum: the "lipliner sign." It appears most prominently at the edges of solid organs (such as the liver and the spleen), which is the same location most likely to show free fluid in FAST examination in trauma patients. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians who take care of trauma patients must be familiar with causes of false positive FAST examinations that could lead to a misdiagnosis of hemoperitoneum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Advanced colorectal cancer (CRC) responds poorly to current adjuvant therapies, partially due to its immunosuppressive intestinal microenvironment. We found that myeloid-derived suppressor cells (MDSCs) were enriched in orthotopic tumors due to treatment-induced succinate release, which activated tuft cells and upregulated interleukin 25 (IL-25) and interleukin 13 (IL-13). We engineered a cabozantinib (Cabo)-encapsulated and maytansine (DM1)-conjugated synthetic high-density lipoprotein ( E C C D-sHDL) to modulate the tumor microenvironment. DM1 induced immunogenic cell death and promoted the maturation of dendritic cells. Meanwhile, Cabo alleviated DM1-induced succinate release, preventing tuft cell activation, downregulating IL-25 and IL-13 secretion, and reducing intratumoral MDSC infiltration. E C C D-sHDL increased the densities of active cytotoxic T lymphocytes (CTLs) and M1 macrophages in the tumors, effectively inhibiting tumor growth and metastasis, thereby prolonging survival in murine CRC models. Our study sheds light on the mechanism of treatment-induced immunosuppression in orthotopic CRC and demonstrates that this combinatorial therapy could be an effective treatment for CRC., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Ainuovirine, as a third-generation non-nucleoside reverse transcriptase inhibitor against HIV-1, is widely used in China. To evaluate its therapeutic efficacy and disadvantages, a comparative study based on Ainuovirine had been conducted., Method: We investigated 199 people living with HIV-1 who received Ainuovirine (ANV)/lamivudine/tenofovir and 202 people living with HIV-1 who received Efavirenz (EFV)/lamivudine/tenofovir., Results: After 48 weeks of therapy, ANV and EFV showed similar viral inhibitory effects. However, in the ANV group, more participants had CD4/CD8 ratios restored to the normal range, lower levels of triglycerides and low-density lipoprotein, relatively normal liver alanine aminotransferase, and fewer adverse events., Conclusion: Therefore, due to its role in immune reconstitution, dyslipidemia, and safety, ANV may be a recommended option for people living with HIV-1., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Clinical observational studies have suggested hyperlipidemia may disturb embryo implantation through endometrium; however, the mechanism has been unclear. With its profound implications for reproductive health, the present study aims to investigate whether hyperlipidemia affects endometrial epithelial cell tight junctions for implantation failures. By constructing hyperlipidemia mice model, the number and distribution of embryo implantation status were investigated after both natural mating and in vitro fertilization and embryo transfer (IVF-ET). Transmission electron microscopy (TEM) was used to compare the ultrastructure of tight junctions in endometrial endothelial cells. Western blot and immunofluorescence were used to explore the expression and localization of tight junction proteins, such as Claudin (CDLN)3, CLDN4, occludin (OCLN), and zonula occludens-1 (ZO1). For women with reproductive failure, mid-luteal phase endometrial tissues were collected, and gene expression of tight junction proteins was investigated using RNA sequencing and qRT-PCR. In hyperlipidemic mice, the number of embryo implantation sites significantly decreased with uneven distribution after natural mating and IVF-ET. Disrupted tight junctions were found, characterized by a decreased number of tight junctions by TEM, downregulated expressions of CDLN4, OCLN, and ZO1, and an increased expression of CLDN3 by western blot. In hyperlipidemic women with reproductive failure, the dysregulated expression of CLDN3 and CLDN4 was also present in the luteal phase endometrium. In this study, evaluation of both animal models and infertile women in vivo demonstrated that hyperlipidemia reduced female fertility, accompanied by disruption of tight junction structures and dysregulation of CLDN3 and CLDN4 expression in the endothelial cells of luteal phase endometrium., Competing Interests: Declaration of Competing Interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Soil health is integral to sustainable agroecosystem management. Current monitoring and assessment practices primarily focus on soil physicochemical properties, yet the perspective of multitrophic biodiversity remains underexplored. Here we used environmental DNA (eDNA) technology to monitor multitrophic biodiversity in four typical agroecosystems, and analyzed the species composition and diversity changes in fungi, bacteria and metazoan, and combined with the traditional physicochemical variables to establish a soil health assessment framework centered on biodiversity data. First, eDNA technology detected rich multitrophic biodiversity in four agroecosystems, including 100 phyla, 273 classes, 611 orders, 1026 families, 1668 genera and 1146 species with annotated classification, and the relative sequence abundance of dominant taxa fluctuates tens of times across agroecosystems. Second, significant differences in soil physicochemical variables such as organic matter (OM), total nitrogen (TN) and available phosphorus (AP) were observed among different agroecosystems, nutrients were higher in cropland and rice paddies, while heavy metals were higher in fish ponds and lotus ponds. Third, biodiversity metrics, including α and β diversity, also showed significant changes across agroecosystems, the soil biota was generally more sensitive to nutrients (e.g., OM, TN or AP), while the fungal communities were mainly affected by heavy metals in October (e.g., Cu and Cr). Finally, we screened 48 sensitive organismal indicators and found significant positive consistency between the developed eDNA indices and the traditional soil quality index (SQI, reaching up to R 2  = 0.58). In general, this study demonstrated the potential of eDNA technology in soil health assessment and underscored the importance of a multitrophic perspective for efficient monitoring and managing agroecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Electroacupuncture has been demonstrated to mitigate endotoxin-induced acute lung injury by enhancing mitochondrial function. This study investigates whether electroacupuncture confers lung protection through the regulation of mitochondrial quality control mediated by heme oxygenase-1 (HO-1) and the mitochondrial inner membrane protein MIC60. HO-1, an inducible stress protein, is crucial for maintaining mitochondrial homeostasis and protecting against lung injury. MIC60, a key component of the mitochondrial contact site and cristae organizing system, supports mitochondrial integrity. We employed genetic knockout/silencing and cell transfection techniques to model lipopolysaccharide (LPS)-induced lung injury, assessing changes in mitochondrial structure, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and the expression of proteins essential for mitochondrial quality control. Our findings reveal that electroacupuncture alleviates endotoxin-induced acute lung injury and associated mitochondrial dysfunction, as evidenced by reductions in lung injury scores, decreased ROS production, and suppressed expression of proteins involved in mitochondrial fission and mitophagy. Additionally, electroacupuncture enhanced MMP and upregulated proteins that facilitate mitochondrial fusion and biogenesis. Importantly, the protective effects of electroacupuncture were reduced in models with Hmox1 knockout or Mic60 silencing, and in macrophages transfected with Hmox1-siRNA or Mic60-siRNA. Moreover, HO-1 was found to influence MIC60 expression during electroacupuncture preconditioning and LPS challenge, demonstrating that these proteins not only co-localize but also interact directly. In conclusion, electroacupuncture effectively modulates mitochondrial quality control through the HO-1/MIC60 signaling pathway, offering an adjunctive therapeutic strategy to ameliorate endotoxin-induced acute lung injury in both in vivo and in vitro settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects., Competing Interests: Declarations. Ethics Approval and Consent to Participate: The study was approved by the local ethics committee of First Affiliated Hospital of Wannan Medical College (Wuhu, Anhui, China; animal ethics code: WNMC-RATS-2022067; 07 September 2022). All methods were performed in accordance with the relevant guidelines and regulations. The experiments performed in this study also comply with the ARRIVE guidelines 2.0 ( https://arriveguidelines.org/ ). Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Context: Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities., Objective: This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro ., Materials and Methods: Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 μg/mL) and NMN (500 μM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups ( n  = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD + and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected., Results: In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD + and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization., Conclusions: NMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within E1 or E3 genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both in vitro and in vivo and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) - follicular helper T (Tfh) cells - germinal centre (GC) / memory B cells (MBCs) - long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the E1 and E3 genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.

Vaccination strategies that can induce a broad spectrum immune response are important to enhance protection against SARS-CoV-2 variants. We conducted a randomized, double-blind and parallel controlled trial to evaluate the safety and immunogenicity of the bivalent (5×10 10 viral particles) and B.1.1.529 variant (5×10 10 viral particles) adenovirus type-5 (Ad5) vectored COVID-19 vaccines administrated via inhalation. 451 eligible subjects aged 18 years and older who had been vaccinated with three doses inactivated COVID-19 vaccines were randomly assigned to inhale one dose of either B.1.1.529 variant Ad5 vectored COVID-19 vaccine (Ad5-nCoVO-IH group, N=150), bivalent Ad5 vectored COVID-19 vaccine (Ad5-nCoV/O-IH group, N=151), or Ad5 vectored COVID-19 vaccine (5×10 10 viral particles; Ad5-nCoV-IH group, N=150). Adverse reactions reported by 37 (24.67%) participants in the Ad5-nCoVO-IH group, 28 (18.54%) in the Ad5-nCoV/O-IH group, and 26 (17.33%) in the Ad5-nCoV-IH group with mainly mild to moderate dry mouth, oropharyngeal pain, headache, myalgia, cough, fever and fatigue. No serious adverse events related to the vaccine were reported. Investigational vaccines were immunogenic, with significant difference in the GMTs of neutralizing antibodies against Omicron BA.1 between Ad5-nCoV/O-IH (43.70) and Ad5-nCoV-IH (29.25) at 28 days after vaccination (P=0.0238). The seroconversion rates of neutralizing antibodies against BA.1 in Ad5-nCoVO-IH, Ad5-nCoV/O-IH, and Ad5-nCoV-IH groups were 56.00%, 59.60% and 48.67% with no significant difference among the groups. Overall, the investigational vaccines were demonstrated to be safe and well tolerated in adults, and was highly effective in inducing mucosal immunities in addition to humoral and cellular immune responses defending against SARS-CoV-2 variants.Trial registration: Chictr.org identifier: ChiCTR2200063996.

Hyperglycemia provides a favorable breeding ground for bacteria, resulting in repeated and persistent inflammation of wounds and prolonged healing processes. In this study, platinum (Pt) nanoparticles (NPs) and glucose oxidase (GOx) were decorated on the surface of camelina lipid droplets (OB) linked with hFGF2, forming PGOB through in situ reduction of Pt ions and electrostatic adsorption, respectively. PGOB exhibits cascade enzyme catalytic activity, which can be activated by glucose in diabetic wound tissues. Specifically, GOx on PGOB catalyzes glucose into hydrogen peroxide, which can further decompose into hydroxyl radicals that have higher toxicity for bacterial inactivation. Additionally, glucose decomposition creates a low pH microenvironment, facilitating the cascade catalytic activity that ensures better bacterial suppression within the wound tissues. Furthermore, hFGF2 promotes the proliferation and migration of fibroblasts. Both in vitro and in vivo experiments confirm that PGOB effectively accelerates wound healing processes through bacteria inactivation and tissue regeneration. This study has developed an alternative strategy for glucose-triggered synergistic cascade therapy for diabetic wounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This article describes the case of a patient with CHARGE syndrome. The clinical data of the patient as well as the whole-genome sequencing results of the child and parents were retrospectively analyzed to determine the pathogenicity of the gene mutation. Genetic testing revealed a heterozygous mutation of the CHD7 gene NM&#95;017780.4: C.4853G >A (P.TP1618ter) in the child, which was identified as a de novo pathogenic mutation. Through this case, we conclude that genetic testing is crucial for accurate diagnosis of deafness. Moreover, paying attention to hearing screening in childhood and strengthening the cognitive level of diagnosis and treatment of syndromic deafness in multiple disciplines can effectively realize early detection, early diagnosis, early intervention, and early rehabilitation of syndromic deafness., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Rhodamine, a colorant prohibited in various consumer products due to its demonstrated carcinogenic, mutagenic, and toxic properties, necessitates the development of a straightforward, efficient, sensitive, environmentally friendly, and cost-effective analytical method. This review provides an overview of recent advancements in the pretreatment and determination techniques for rhodamine across diverse sample matrices since 2017. Sample preparation methods encompass both commonly used pretreatment techniques such as filtration, centrifugation, solvent extraction, and cloud point extraction, as well as innovative approaches including solid phase extraction, dispersive liquid-liquid microextraction, hollow fiber liquid phase microextraction, magnetic solid phase extraction, and matrix solid phase dispersion. The analytical techniques encompass high performance liquid chromatography, surface-enhanced Raman scattering, and sensor-based methods. Furthermore, a comprehensive examination is conducted to offer insights for future research on rhodamine regarding the advantages, disadvantages, and advancements in various pretreatment and determination methodologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The intestinal immune system is the largest immune organ in the human body. Excessive immune response to intestinal cavity induced by harmful stimuli including pathogens, foreign substances and food antigens is an important cause of inflammatory diseases such as celiac disease and inflammatory bowel disease (IBD). Although great progress has been made in the treatment of IBD by some immune-related biotherapeutic products, yet a considerable proportion of IBD patients remain unresponsive or immune tolerant to immunotherapeutic strategy. Therefore, it is necessary to further understand the mechanism of immune cell populations involved in enteritis, including dendritic cells, macrophages and natural lymphocytes, in the steady-state immune tolerance of IBD, in order to find effective IBD therapy. In this review, we discussed the important role of innate and adaptive immunity in the development of IBD. And the relationship between intestinal immune system disorders and microflora crosstalk were also presented. We also focus on the new findings in the field of T cell immunity, which might identify novel cytokines, chemokines or anti-cytokine antibodies as new approaches for the treatment of IBD., Competing Interests: The authors declare no competing conflict of interest in this work., (© 2024 Yue et al.)

Percutaneous coronary intervention (PCI) is an effective method for the treatment of coronary heart disease. Cardiac rehabilitation and continuous nursing management after discharge are the key to ensure the quality of treatment and the quality of life of patients. This study aimed to explore the significance of WeChat platform in continuous care after PCI. We collected the clinical data of 90 PCI patients in 2 centers from January 2020 to July 2023, and divided the patients into 2 groups: the continuous nursing care group based on the WeChat platform and the control group. Continuous nursing care was implemented immediately after discharge. After 1-year follow-up, we compared the outcomes of the 2 groups, including postoperative complications, lifestyle changes and psychological status. There were no heart-related postoperative complications in either group. The incidence of vagal reflex was significantly decreased in the continuous nursing group (P = .042). The improvement of life style, such as smoking cessation (P = .001) and alcohol withdrawal (P = .003), was significantly better than that of the control group. The continuous nursing group was better than the control group in improving psychological status based on the Hamilton's depression scale. Continuous nursing care based on WeChat platform could reduce the incidence of complications of patients after PCI, alleviate patients' depression, and improve patients' quality of life., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Iron oxide nanoparticles (MNPs) demonstrate notable benefits in magnetic induction, attributed to their distinctive physical and chemical attributes. Emerging cancer treatment utilizing magnetic fields have also gathered increasing attention in the biomedical field. However, the defects of difficult dispersion and poor biocompatibility of MNPs seriously hinder their application. In order to overcome its inherent defects and maximize the therapeutic potential of MNPs, various functionalized MNPs have been developed, and numerous combined treatment methods based on MNPs have been widely studied. In this review, we compare and analyze the common nanoparticles based on MNPs with different sizes, shapes, and functional modifications. Additionally, we introduced the therapeutic mechanisms of the strategies, such as magnetically controlled targeting, magnetic hyperthermia, and magneto-mechanical effect, which based on the unique magnetic induction capabilities of MNPs. Finally, main challenges of MNPs as smart nanomaterials were also discussed. This review seeks to offer a thorough overview of MNPs in biomedicine and a new sight for their application in tumor treatment., (© 2024 The Chemical Society of Japan and Wiley-VCH GmbH.)

Objective: The coexistence of depression and chronic diseases might lead to greater disability and increased mortality, and the American Heart Association (AHA) recently proposed Life's Essential 8 (LE8) score to quantify cardiovascular health (CVH). The study aimed to examine the association between LE8 and depression among adults with chronic diseases and comorbidity., Methods: 14,029 adults with chronic diseases from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were included in the study. Overall LE8 and subscale scores were categorized into low, moderate, and high groups. Multivariate logistic regressions were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between LE8 and depression among adults with various chronic diseases and comorbidity., Results: After adjusting for all covariates, compared to low CVH, high CVH was associated with a significantly lower presence of depressive symptoms among adults with diabetes [OR (95% CI), 0.25 (0.11, 0.58)], hypertension [0.27 (0.20, 0.36)], coronary heart disease [0.16 (0.07, 0.36)], stroke [0.29 (0.11, 0.76)], hyperlipidemia [0.24 (0.20, 0.30)], at least one chronic comorbidity [0.25 (0.21, 0.30)], any single chronic condition [0.28 (0.21, 0.38)], and comorbidities [0.27 (0.19, 0.38)]. Similarly, moderate CVH was also associated with a lower presence of depressive symptoms among adults with various chronic diseases and comorbidities. Dose-response relationships were found, revealing that the ORs for depressive symptoms increased with the decrease of the LE8 score and subscale scores among adults with chronic diseases and comorbidities., Conclusion: The prevalence of depression increases with decreasing levels of the LE8 and subscale scores among adults with various chronic diseases and comorbidities in the United States., Competing Interests: Declaration of competing interest The authors have declared no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Although the therapeutic potential of miRNA-mediated gene regulation has been investigated, its precise functional regulatory mechanism in neuropathic pain remains incompletely understood. In this study, we elucidate that miR-216a-3p serves as a critical non-coding RNA involved in the modulation of trigeminal-mediated neuropathic pain. By conducting RNA-seq and qPCR analysis, we observed a notable decrease of miR-216a-3p in the injured trigeminal ganglia (TG) of male rats. Intra-TG administration of miR-216a-3p agomir or lentiviral-mediated overexpression of miR-216a-3p specifically in sensory neurons of injured TGs alleviated established neuropathic pain behaviors, while downregulation of miR-216a-3p (pharmacologically or genetically) in naïve rats induced pain behaviors. Moreover, nerve injury significantly elevated the H3K27 trimethylation (H3K27me3) levels in the ipsilateral TG, thereby suppressing the SRY-box transcription factor 10 (SOX10) binding to the miR-216a-3p promoter and resulting in the reduction of miR-216a-3p. Inhibiting the enzymes that responsible for catalyzing H3K27me3 restored the nerve injury-induced reduction in miR-216a-3p expression and markedly ameliorated neuropathic pain behaviors. Furthermore, miR-216a-3p targeted stromal interaction molecule 1 (STIM1), and the decreased miR-216a-3p associated with neuropathic pain caused a significant upregulation in the protein abundance of STIM1. Conversely, overexpression of miR-216a-3p in the injured TG suppressed the upregulation of STIM1 expression and reversed the mechanical allodynia. Together, the mechanistic understanding of H3K27me3-dependent SOX10/miR-216a-3p/STIM1 signaling axial in sensory neurons may facilitate the discovery of innovative therapeutic strategies for neuropathic pain management. Significance Statement miRNAs are posttranscriptional regulators of gene expression that play critical roles in the pathogenesis of neuropathic pain. However, the detailed mechanisms by which most pain-associated miRNAs operate and their therapeutic potential are incompletely understood. Our present study revealed that nerve injury-induced trimethylation of lysine 27 on histone H3 (H3K27me3) reduces the binding of SOX10, a transcription factor, to the promoter region of the miR-216a-3p gene, leading to decreased expression of the microRNA, miR-216a-3p. This reduction subsequently promotes neuropathic pain by regulating STIM1. Given that miRNA-mediated gene regulation is a proposed therapeutic approach for treating neuropathic pain, our findings suggest that replenishing miR-216a-3p could serve as a novel strategy for treating chronic neuropathic pain., (Copyright © 2024 the authors.)

The combined effect of cardiovascular risk factors on breast cancer in women is unknown. The relationship between genetic risk combined with cardiovascular health (CVH) levels and breast cancer has not been confirmed. This study aims to explore the relationship between CVH level based on life's essential 8 (LE8) score and breast cancer risk in women with different menopausal statuses and to estimate further the effect of CVH level combined with genetic susceptibility on breast cancer risk. A total of 118,911 women from UK Biobank were included in the study, including 22,676 premenopausal women and 96,235 postmenopausal women. The association between the CVH level and the risk of breast cancer in women with different menopausal statuses was assessed using the Cox proportional hazards regression models, with the healthiest CVH group as the reference. In addition, risk ratios (HRs) and 95% confidence intervals (95% CIs) for the joint effect of the CVH level and polygenic risk score (PRS) were calculated using the PRS from the UK Biobank. During a mean follow-up period of 13.8 years, we observed 733 cases and 3,645 cases of breast cancer in premenopausal and postmenopausal women, respectively. In premenopausal women, the risk of breast cancer was significantly increased in the intermediate CVH group (HR, 1.28; 95%CI 1.08-1.52) and the low CVH group (HR, 1.44; 95%CI 1.13-1.85). In postmenopausal women, the risk of incidence was also significantly increased in the intermediate CVH group (HR, 1.20; 95%CI 1.07-1.32) and the low CVH group (HR, 1.34; 95%CI 1.17-1.54). In the joint effect analysis, the risk of breast cancer for women in the low CVH group and the high genetic risk group was highest in both premenopausal (HR, 8.26; 95%CI 4.44-15.35) and postmenopausal (HR, 8.10; 95%CI 5.50-11.93) women. Women with lower LE8 scores and higher genetic susceptibility have the higher risk of breast cancer. This suggests that women with lower levels of CVH and higher genetic susceptibility have an increased risk of breast cancer under different menopausal statuses., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: The study was approved by the North West Multi-center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland ( http://www.ukbiobank.ac.uk/ethics/ ). Informed consent: All participants provided written informed consent before participation in the study. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures., Purpose: The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes., Methods: A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed., Results: A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61-0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for >78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61-0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21-0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments., Conclusion: GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Food workers have frequent contact with unprocessed foods, but their carriage of Salmonella and potential influence on public health have not been comprehensively assessed. We investigated Salmonella carriage among food workers compared with non-food workers based on occupational health screening of 260,315 asymptomatic workers over an 8-year surveillance period in Yulin, China. We confirmed that healthy carriers serve as natural reservoirs for Salmonella, with higher carriage rates in food workers than non-food workers. The isolates from food workers also exhibited greater serovar diversity and likely higher levels of antimicrobial resistance than those from non-food workers. Factors such as meteorological, social, and hygiene factors potentially influenced the carriage rate. Genomic analysis revealed a consistent increase in antimicrobial resistance genes among Salmonella isolates over the study period, with the majority of these antimicrobial resistance genes located on plasmids. Additionally, we identified numerous closely related bacterial clusters, which might reflect clusters of hidden local foodborne infections. This study underscores the elevated risk posed by food workers in the persistence and dissemination of Salmonella as vectors/fomites. Enhanced monitoring and targeted interventions in this group may reduce the dissemination of pathogens and antimicrobial resistance genes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Existing evidence suggests that miscarriage and stillbirth are associated with an increased risk of stroke in women. However, the impact of these events on stroke mortality remains unclear. This study aimed to elucidate the potential association between miscarriage and stillbirth and stroke mortality in women., Methods: We employed a competing risk model using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial to assess the relationship between miscarriage/stillbirth and stroke death. Death from other causes was considered as a competing risk, and we conducted a subgroup analysis to explore the potential impact., Results: Our study included 68,629 women for miscarriage and 65,343 women for stillbirth. No significant association was observed between miscarriage and stroke mortality (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.84-1.10; p=0.58). While a single stillbirth did not show a significant association (HR=1.07; 95% CI, 0.81-1.41, p=0.63), recurrent stillbirth (≥2) was associated with a significantly increased risk of stroke mortality compared to women with no stillbirths (HR=2.24; 95% CI, 1.45-3.46, p<0.001)., Conclusion: Our findings suggest that recurrent stillbirth, but not single events, is associated with an elevated risk of stroke mortality in women. Further research is warranted to clarify the underlying mechanisms and potential long-term health implications of recurrent pregnancy loss.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy and the only curable therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT is not appropriate for all CMML patients, and relapse is the leading cause of treatment failure. This project conducted a nationwide multicenter real-world study to develop a novel prediction scoring system for early relapse. A total of 238 CMML patients from twenty-seven medical centers treated with allo-HSCT, and 307 adult patients with CMML who underwent allo-HSCT in a publicly available research dataset from the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database were included. Independent prognostic factors for the early relapse of CMML posttransplantation were identified according to competing risk regression methods. Four prognostic factors were identified: bone marrow blasts >10% (hazard ratio [HR], 4.262; P = 0.014), age >60 years (HR, 6.221; P = 0.007), hemoglobin level <100 g/L (HR, 3.695; P = 0.004), and non TET2 gene mutation (HR, 3.425; P = 0.017). A risk-grading scoring system was developed based on the regression coefficients and patients were stratified into low-risk (0-1 point), intermediate-risk (1.5-2 points) and high-risk ( > 2 points) groups. The validated internal c-statistic was 0.767 (95% confidence interval [CI], 0.674-0.860), and the external c-statistic was 0.769 (95% CI, 0.703-0.836). In the derivation cohort, the cumulative incidence rates of early relapse in the low-risk, intermediate-risk, and high-risk groups were 1.35% (95% CI: 1-4%), 10.40% (95% CI: 4-16%), and 29.54% (95% CI: 16-39%) (P < 0.001), respectively. This scoring system can be utilized to early identification of patients at a high risk of relapse and contributing to the implementation of urgent medical support., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)