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Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions and biomarkers to address oxidative stress and neuroinflammation in these conditions are limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence as a potential target in neurodegenerative diseases. Soluble UA stands out as one of the most vital antioxidant compounds produced by the human body, accounting for up to 55% of the extracellular capacity to neutralize free radicals. While there is increasing evidence supporting the neuroprotective properties of UA in Parkinson's disease and Alzheimer's disease, gaps in knowledge still exist regarding the underlying mechanisms and how to effectively translate these benefits into clinical practice. Moreover, the current UA elevation therapy exhibits unstable antioxidant properties, individual variability, and even adverse effects, limiting its potential clinical applications. This review consolidates recent advancements in understanding how UA exerts neuroprotective effects on neurodegenerative diseases and emphasizes the dual roles of UA in managing oxidative stress and neuroinflammation. Additionally, the review elucidates the mechanisms through which UA confers neuroprotection. Based on this, the review underscores the significance of UA as a potential biomarker and aims to provide a comprehensive understanding of its potential as a therapeutic target, while also addressing possible challenges to clinical implementation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Chimeric antigen receptor T (CAR-T) cell therapy has shown remarkable success in hematologic malignancies but has encountered challenges in effectively treating solid tumors. One major obstacle is the presence of the immunosuppressive tumor microenvironment (TME), which is mainly built by myeloid-derived suppressor cells (MDSCs). Recent studies have shown that MDSCs have a detrimental effect on CAR-T cells due to their potent immunosuppressive capabilities. Targeting MDSCs has shown promising results to enhance CAR-T immunotherapy in preclinical solid tumor models. In this review, we first highlight that MDSCs increase tumor proliferation, transition, angiogenesis and encourage circulating tumor cells (CTCs) extravasation leading to tumor progression and metastasis. Moreover, we describe the main characteristics of the immunosuppressive activities of MDSCs on T cells in TME. Most importantly, we summarize targeting therapeutic strategies of MDSCs in CAR-T therapies against solid tumors. These strategies include (1) therapeutic targeting of MDSCs through small molecule inhibitors and large molecule antibodies; (2) CAR-T targeting cancer cell antigen combination with MDSC modulatory agents; (3) cytokine receptor antigen-targeted CAR-T indirectly or directly targeting MDSCs reshapes TME; (4) modified natural killer (NK) cells expressing activating receptor directly targeting MDSCs; and (5) CAR-T directly targeting MDSC selective antigens. In the near future, we are expected to witness the improvement of CAR-T cell therapies for solid tumors by targeting MDSCs in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: The review did not involve any primary data collection or human subjects research, thus eliminating the need for ethical approval and participant consent. Consent for publication: All authors have agreed to publish this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: CMTM6 has been closely associated with the onset and progression of various tumor types. However, the precise mechanism by which CMTM6 operates in hepatocellular carcinoma remains elusive, necessitating further investigation., Methods: Expression levels of CMTM6 in hepatocellular carcinoma tissues and cells were analyzed using immunohistochemistry and quantitative real-time PCR. The correlation between CMTM6 expression in hepatocellular carcinoma tissues and clinical pathological characteristics, as well as patient prognosis, was investigated. Proliferation and apoptosis of hepatocellular carcinoma cells with silenced or overexpressed CMTM6 were assessed, alongside measurements of β-catenin and Wnt1 protein expression levels. In vivo research was conducted utilizing a murine subcutaneous transplantation model. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to elucidate the regulatory mechanism of CMTM6. Additionally, CD66b expression levels in tumor tissue were examined using immunohistochemistry, and the immune infiltration of CMTM6 and tumor-associated neutrophils (TANs) was analyzed., Results: Elevated expression levels of CMTM6 in hepatocellular carcinoma tissues and cells were found to be associated with poor patient prognosis. Overexpression of CMTM6 in hepatocellular carcinoma cells was demonstrated to promote cellular proliferation and inhibit apoptosis. Mechanistically, CMTM6 expression levels in hepatocellular carcinoma tissues were observed to positively correlate with β-catenin expression. GSEA and KEGG analysis revealed significant enrichment of CMTM6 in the Wnt/β-catenin pathway, indicating its involvement in pathway regulation. Furthermore, CMTM6 was found to be associated with immune infiltration of TANs in hepatocellular carcinoma tissues., Conclusion: CMTM6 plays a pivotal role in the development and progression of hepatocellular carcinoma through regulation of the Wnt/β-catenin pathway via β-catenin. Moreover, CMTM6 demonstrates the capacity to promote immune infiltration of TANs in hepatocellular carcinoma tissues. Consequently, CMTM6 exhibits potential as both an early diagnostic marker and a novel therapeutic target for patients with hepatocellular carcinoma., Competing Interests: Declarations. Ethics approval and consent to participate: This study received approval from the Independent Ethics Committee of Tumor Hospital Affiliated to Xinjiang Medical University in 2023. The ethics approval number is G-2023032. Informed consent: Informed consent was obtained from all individual participants included in this study. The data supporting the conclusions presented in this article are incorporated within the manuscript. The raw datasets utilized and analyses performed in this study are available from the corresponding author upon submission of a reasonable request. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Maintaining iron homeostasis is crucial for preventing the development of colorectal cancer (CRC). However, Evidence regarding the correlation between serum iron status and CRC has been inconsistent. This population-based study aims to explore the potential association between serum iron status and CRC risk., Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) registry spanning from 2001 to 2020, a cross-sectional study involving 9504 participants was performed to assess the relationship between serum iron status and CRC risk. The study encompassed men and women of various racial backgrounds, aged 20 to 80, from across the United States. Participants' characteristics were presented using mean or proportion. The possible risk factor for CRC was examined using both univariable and multivariable analysis. A logistic regression model was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of CRC in accordance with each quantile increment in serum iron item levels., Results: After making full adjustment, our analysis did not reveal a statistically significant association between serum iron, ferritin, transferrin saturation (TSAT), total iron-binding capacity (TIBC) and the risk of CRC. While there was no statistically significant difference observed, an increasing ferritin concentration appeared to be associated with a decreased CRC risk when compared to the lowest quantile. Specifically, the ORs and 95% CIs for the second, third, and fourth quantiles (Q2, Q3, and Q4) versus the lowest quantile (Q1) were as follows: Q2 (vs. Q1) OR 0.403, 95% CI 0.063-2.568; Q3 (vs. Q1) OR 0.316, 95% CI 0.059-1.687; Q4 (vs. Q1) OR 0.250, 95% CI 0.050-1.258. However, this trend did not reach statistical significance (P for trend = 0.381)., Conclusion: Our analyze did not demonstrate a statistically significant correlation between serum iron status and the risk of CRC., 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).)

In order to clarify the chloroplast genomes and structural features of ten Ilex species and provide insights into the phylogeny and genome evolution of the genus Ilex, we conducted a comparative analysis of chloroplast genomes using bioinformatics methods. The chloroplast genomes of ten Ilex species were obtained, and their structural features and variations were compared. The results indicated that all chloroplast genomes in the genus Ilex exhibit a double-stranded circular structure, with sizes ranging from 157,356 to 158,018 bp, showing minimal differences in size. The chloroplast genomes of the ten Ilex species have a relatively conservative gene count, with a total of 134 to 135 genes, including 88 or 89 protein-coding genes, and a conserved number of 8 rRNA genes. Each chloroplast genome contains 3 to 123 SSR (Simple Sequence Repeat) sites, predominantly composed of mononucleotide and trinucleotide repeats, with no detection of pentanucleotide or hexanucleotide repeats. The variation in dispersed repeat sequences among Ilex species is minimal, with a total repeat sequence number ranging from 1 to 14, concentrated in the length range of 30 to 42 base pairs. The expansion and contraction of chloroplast genome boundaries among Ilex species are relatively stable, with only minor variations observed in individual species. Variations in non-coding regions are more pronounced than those in coding regions, with the variability in the Large Single Copy region (LSC) being the highest, while the variability in the Inverted Repeat region A (IRa) is the lowest. The divergence time among Ilex species was estimated using the MCMC-tree module, revealing the evolutionary relationships among these species, their common ancestors, and their differentiation throughout the evolutionary process. The research findings provide a valuable reference for the systematic study and molecular marker development of Ilex plants., (© 2024. The Author(s).)

Tryptophan (Trp) metabolism involves three primary pathways: the kynurenine (Kyn) pathway (KP), the 5-hydroxytryptamine (serotonin, 5-HT) pathway, and the indole pathway. Under normal physiological conditions, Trp metabolism plays crucial roles in regulating inflammation, immunity, and neuronal function. Key rate-limiting enzymes such as indoleamine-2,3-dioxygenase (IDO), Trp-2,3-dioxygenase (TDO), and kynurenine monooxygenase (KMO) drive these metabolic processes. Imbalances in Trp metabolism are linked to various cancers and often correlate with poor prognosis and adverse clinical characteristics. Dysregulated Trp metabolism fosters tumor growth and immune evasion primarily by creating an immunosuppressive tumor microenvironment (TME). Activation of the KP results in the production of immunosuppressive metabolites like Kyn, which modulate immune responses and promote oncogenesis mainly through interaction with the aryl hydrocarbon receptor (AHR). Targeting Trp metabolism therapeutically has shown significant potential, especially with the development of small-molecule inhibitors for IDO1, TDO, and other key enzymes. These inhibitors disrupt the immunosuppressive signals within the TME, potentially restoring effective anti-tumor immune responses. Recently, IDO1 inhibitors have been tested in clinical trials, showing the potential to enhance the effects of existing cancer therapies. However, mixed results in later-stage trials underscore the need for a deeper understanding of Trp metabolism and its complex role in cancer. Recent advancements have also explored combining Trp metabolism inhibitors with other treatments, such as immune checkpoint inhibitors, chemotherapy, and radiotherapy, to enhance therapeutic efficacy and overcome resistance mechanisms. This review summarizes the current understanding of Trp metabolism and signaling in cancer, detailing the oncogenic mechanisms and clinical significance of dysregulated Trp metabolism. Additionally, it provides insights into the challenges in developing Trp-targeted therapies and future research directions aimed at optimizing these therapeutic strategies and improving patient outcomes., (© 2024. The Author(s).)

The advancement of precision radiotherapy techniques, such as volumetric modulated arc therapy (VMAT), stereotactic body radiotherapy (SBRT), and particle therapy, highlights the importance of radiotherapy in the treatment of cancer, while also posing challenges for respiratory motion management in thoracic and abdominal tumors. MRI-guided radiotherapy (MRIgRT) stands out as state-of-art real-time respiratory motion management approach owing to the non-ionizing radiation nature and superior soft-tissue contrast characteristic of MR imaging. In clinical practice, MR imaging often operates at a frequency of 4 Hz, resulting in approximately a 300 ms system latency of MRIgRT. This system latency decreases the accuracy of respiratory motion management in MRIgRT. Artificial intelligence (AI)-based respiratory motion prediction has recently emerged as a promising solution to address the system latency issues in MRIgRT, particularly for advanced contour prediction and volumetric prediction. However, implementing AI-based respiratory motion prediction faces several challenges including the collection of training datasets, the selection of prediction methods, and the formulation of complex contour and volumetric prediction problems. This review presents modeling approaches of AI-based respiratory motion prediction in MRIgRT, and provides recommendations for achieving consistent and generalizable results in this field., (© 2024. The Author(s).)

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) is a common and important post-translational modification (PTM) linking O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and threonine residues in proteins. Extensive research indicates its impact on target protein stability, activity, and interactions. O-linked N-acetylglucosamine transferase (OGT) is a critical enzyme that catalyzes O-GlcNAc modification, responsible for adding O-GlcNAc to proteins. OGT and O-GlcNAcylation are overexpressed in many tumors and closely associated with tumor growth, invasion, metabolism, drug resistance, and immune evasion. This review delineates the biochemical functions of OGT and summarizes its effects and mechanisms in tumors. Targeting OGT presents a promising novel approach for treating human malignancies., (© 2024. The Author(s).)

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing to this resistance is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), and adenosine-to-inosine (A-to-I) editing. These modifications are pivotal in regulating RNA splicing, translation, transport, degradation, and stability. Governed by "writers," "readers," and "erasers," RNA modifications impact numerous biological processes and cancer progression, including cell proliferation, stemness, autophagy, invasion, and apoptosis. Aberrant RNA modifications can lead to drug resistance and adverse outcomes in various cancers. Thus, targeting RNA modification regulators offers a promising strategy for overcoming drug resistance and enhancing treatment efficacy. This review consolidates recent research on the role of prevalent RNA modifications in cancer drug resistance, with a focus on m6A, m1A, m5C, m7G, Ψ, and A-to-I editing. Additionally, it examines the regulatory mechanisms of RNA modifications linked to drug resistance in cancer and underscores the existing limitations in this field., (© 2024. The Author(s).)

Epothilone B (Epo B), a promising antitumor compound effective against various types of cancer cells in vitro. However, its poor selectivity for tumor cells and inadequate therapeutic windows significantly limit its potential clinical application. Affibody is a class of non-immunoglobulin affinity proteins with precise targeting capability to overexpressed molecular receptors on cancer cells, has been intensively investigated due to its exceptional affinity properties. In this study, we present a targeted nanoagent self-assembled from the precursor of an affibody conjugated with Epo B via a linker containing the thioketal (tk) group that is sensitive to reactive oxygen species (ROS). The core-shell structure of the Z HER2:342 -Epo B Affibody-Drug Conjugate Nanoagent (Z-E ADCN), with the cytotoxin Epo B encapsulated within the Z HER2:342 affibody corona, leads to significantly reduced side effects on normal organs. Moreover, the abundant presence of Z HER2:342 on the surface effectively enhances the targeting capacity and tumor accumulation of the drug. Z-E ADCN can be internalized by cancer cells via HER2 receptor-mediated endocytosis followed by Epo B release in response to high levels of ROS, resulting in excellent anticancer efficacy in HER2-positive tumor models., (© 2024. The Author(s).)

Background: Surgery is the main treatment option for destroyed-lung (DL) patients with life-threatening massive hemoptysis. However, short-term and long-term surgical safety and efficacy are unclear, prompting this study., Methods: Data from 124 DL patients undergoing surgery between November 2001 and January 2022 at Beijing Chest Hospital were retrospectively analyzed. Data of the DL group (82 cases) and DL + massive hemoptysis group (42 cases) were compared with regard to clinical characteristics, long-term postoperative residual lung reinfection., Results: As compared with DL group rates, The DL + massive hemoptysis group had greater incidence rates of postoperative complications, invasive postoperative respiratory support, long-term postoperative residual lung reinfection, and postoperative tuberculosis recurrence. Revealed risk factors for postoperative complications (Extent of lung lesion resection), postoperative invasive respiratory therapy (preoperative Hb < 9 g/L, severe intraoperative hemoptysis), and postoperative long-term residual lung reinfection (DL with massive hemoptysis)., Conclusions: DL patients with massive hemoptysis had greater rate of invasive respiratory support therapy and postoperative complications. Extensive lesion removal, preoperative anaemia, severe intraoperative bleeding associated with recent postoperative complications for the patient., (© 2024. The Author(s).)

Background: In the field of ornamental horticulture, phenotypic mutations, particularly in leaf color, are of great interest due to their potential in developing new plant varieties. The introduction of variegated leaf traits in plants like Heliopsis helianthoides, a perennial herbaceous species with ecological adaptability, provides a rich resource for molecular breeding and research on pigment metabolism and photosynthesis. We aimed to explore the mechanism of leaf variegation of Heliopsis helianthoides (using HY2021F1-0915 variegated mutant named HY, and green-leaf control check named CK in 2020 April, May and June) by analyzing the transcriptome and metabolome., Results: Leaf color and physiological parameters were found to be significantly different between HY and CK types. Chlorophyll content of HY was lower than that of CK samples. Combined with the result of Weighted Gene Co-expression Network Analysis (WGCNA), 26 consistently downregulated differentially expressed genes (DEGs) were screened in HY compared to CK subtypes. Among the DEGs, 9 genes were verified to be downregulated in HY than CK by qRT-PCR. The reduction of chlorophyll content in HY might be due to the downregulation of FSD2. Low expression level of PFE2, annotated as ferritin-4, might also contribute to the interveinal chlorosis of HY. Based on metabolome data, differential metabolites (DEMs) between HY and CK samples were significantly enriched on ABC transporters in three months. By integrating DEGs and DEMs, they were enriched on carotenoids pathway. Downregulation of four carotenoid pigments might be one of the reasons for HY's light color., Conclusion: FSD2 and PFE2 (ferritin-4) were identified as key genes which likely contribute to the reduced chlorophyll content and interveinal chlorosis observed in HY. The differential metabolites were significantly enriched in ABC transporters. Carotenoid biosynthesis pathway was highlighted with decreased pigments in HY individuals. These findings not only enhance our understanding of leaf variegation mechanisms but also offer valuable insights for future plant breeding strategies aimed at preserving and enhancing variegated-leaf traits in ornamental plants., (© 2024. The Author(s).)

Background: With the rapid development of single-cell sequencing technology, histological studies are no longer limited to conventional homogenized tissues. Laser microdissection enables the accurate isolation of specific tissues or cells, and when combined with next-generation sequencing, it can reveal important biological processes at the cellular level. However, traditional laser microdissection techniques have often been complicated and time-consuming, and the quality of the RNA extracted from the collected samples has been inconsistent, limiting follow-up studies. Therefore, an improved, simple, and efficient laser microdissection method is urgently needed., Results: We omitted the sample fixation and cryoprotectant addition steps. Instead, fresh samples were embedded in Optimal Cutting Temperature medium within 1.5 ml centrifuge tube caps, rapidly frozen with liquid nitrogen, and immediately subjected to cryosectioning. A series of section thicknesses of citrus rind were tested for RNA extraction, which showed that 18 μm thickness yielded the highest quality RNA. By shortening the dehydration time to one minute per ethanol gradient and omitting the tissue clearing step, the resulting efficient dehydration and preserved morphology ensured high-quality RNA extraction. We also propose a set of laser microdissection parameters by adjusting the laser power to optimal values, reducing the aperture size, and lowering the pulse frequency. Both the epidermal and subepidermal cells from the citrus rind were collected, and RNA extraction was completed within nine hours. Using this efficient method, the transcriptome sequencing of the isolated tissues generated high-quality data with average Q30 values and mapping rates exceeding 91%. Moreover, the transcriptome analysis revealed significant differences between the cell layers, further confirming the effectiveness of our isolation approach., Conclusions: We developed a simple and rapid laser microdissection method and demonstrated its effectiveness through a study based on citrus rind, from which we generated high-quality transcriptomic data. This fast and efficient method of cell isolation, combined with transcriptome sequencing not only contributes to precise histological studies at the cellular level in citrus but also provides a promising approach for cell-specific transcriptome analysis in a broader range of other plant tissues., (© 2024. The Author(s).)

Background: Idiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown., Methods: We recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites., Results: We detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9-100%]) by receiver operating characteristic (ROC) analysis., Conclusion: Our study suggests that the microbiome and the microbial-derived metabolites play certain roles in children's growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS., (© 2024. The Author(s).)

Background: Single cell RNA sequencing technology (scRNA-seq) has been proven useful in understanding cell-specific disease mechanisms. However, identifying genes of interest remains a key challenge. Pseudo-bulk methods that pool scRNA-seq counts in the same biological replicates have been commonly used to identify differentially expressed genes. However, such methods may lack power due to the limited sample size of scRNA-seq datasets, which can be prohibitively expensive., Results: Motivated by this, we proposed to use the Bayesian-frequentist hybrid (BFH) framework to increase the power and we showed in simulated scenario, the proposed BFH would be an optimal method when compared with other popular single cell differential expression methods if both FDR and power were considered. As an example, the method was applied to an idiopathic pulmonary fibrosis (IPF) case study., Conclusion: In our IPF example, we demonstrated that with a proper informative prior, the BFH approach identified more genes of interest. Furthermore, these genes were reasonable based on the current knowledge of IPF. Thus, the BFH offers a unique and flexible framework for future scRNA-seq analyses., (© 2024. The Author(s).)

The vaginal microbiome is an immune defense against reproductive diseases and can serve as an important biomarker for cervical cancer. However, the intrinsic relationship between the recurrence and the vaginal microbiome in patients with cervical cancer before and after concurrent chemoradiotherapy is poorly understood. Here, we analyzed 125 vaginal microbial profiles from a patient cohort of stage IB-IVB cervical cancer using 16S metagenomic sequencing and deciphered the microbial composition and functional characteristics of the recurrent and non-recurrent both before and after chemoradiotherapy. We demonstrated that the abundance of beneficial bacteria and stability of the microbial community in the vagina decreased in the recurrence group, implying the unique characteristics of the vaginal microbiome for recurrent cervical cancer. Moreover, using machine learning, we identified Lactobacillus iners as the most important biomarker, combined with age and other biomarkers (such as Ndongobacter massiliensis, Corynebacterium pyruviciproducens ATCC BAA-1742, and Prevotella buccalis), and could predict cancer recurrence phenotype before chemoradiotherapy. This study prospectively employed rigorous bioinformatics analysis and highlights the critical role of vaginal microbiota in post-treatment cervical cancer recurrence, identifying promising biomarkers with prognostic significance in the context of concurrent chemoradiotherapy for cervical cancer. The role of L. iners in determining chemoradiation resistance in cervical cancer warrants further detailed investigation. Our results expand our understanding of cervical cancer recurrence and help develop better strategies for prognosis prediction and personalized therapy., (© 2024. The Author(s).)

Background: Carcass traits are essential economic traits in the commercial pig industry. However, the genetic mechanism of carcass traits is still unclear. In this study, we performed a genome-wide association study (GWAS) based on the specific-locus amplified fragment sequencing (SLAF-seq) to study seven carcass traits on 223 four-way intercross pigs, including dressing percentage (DP), number of ribs (RIB), skin thinkness (ST), carcass straight length (CSL), carcass diagonal length (CDL), loin eye width (LEW), and loin eye thickness (LET)., Results: A total of 227,921 high-quality single nucleotide polymorphisms (SNPs) were detected to perform GWAS. A total of 30 SNPs were identified for seven carcass traits using the mixed linear model (MLM) (p < 1.0 × 10 - 5 ), of which 9 SNPs were located in previously reported quantitative trait loci (QTL) regions. The phenotypic variation explained (PVE) by the significant SNPs was from 2.43 to 16.32%. Furthermore, 11 candidate genes (LYPLAL1, EPC1, MATN2, ZFAT, ZBTB10, ZNF704, INHBA, SMYD3, PAK1, SPTBN2, and ACTN3) were found for carcass traits in pigs., Conclusions: The GWAS results will improve our understanding of the genetic basis of carcass traits. We hypothesized that the candidate genes associated with these discovered SNPs would offer a biological basis for enhancing the carcass quality of pigs in swine breeding., (© 2024. The Author(s).)

Background: Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery., Methods: A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study., Results: Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful., Conclusion: JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients., (© 2024. The Author(s).)

Background: Postpartum women often experience stress urinary incontinence (SUI) and vaginal microbial dysbiosis, which seriously affect women's physical and mental health. Understanding the relationship between SUI and vaginal microbiota composition may help to prevent vaginal diseases, but research on the potential association between these conditions is limited., Results: This study employed 16S rRNA gene sequencing to explore the association between SUI and vaginal dysbiosis. In terms of the vaginal microbiota, both species richness and evenness were significantly higher in the SUI group. Additionally, the results of NMDS and species composition indicated that there were differences in the composition of the vaginal microbiota between the two groups. Specifically, compared to postpartum women without SUI (Non-SUI), the relative abundance of bacteria associated with bacterial dysbiosis, such as Streptococcus, Prevotella, Dialister, and Veillonella, showed an increase, while the relative abundance of Lactobacillus decreased in SUI patients. Furthermore, the vaginal microbial co-occurrence network of SUI patients displayed higher connectivity, complexity, and clustering., Conclusion: The study highlights the role of Lactobacillus in maintaining vaginal microbial homeostasis. It found a correlation between SUI and vaginal microbiota, indicating an increased risk of vaginal dysbiosis. The findings could enhance our understanding of the relationship between SUI and vaginal dysbiosis in postpartum women, providing valuable insights for preventing bacterial vaginal diseases and improving women's health., (© 2024. The Author(s).)

Background: Gene flow is crucial for enhancing economic traits of livestock. In China, breeders have used hybridization strategies for decades to improve livestock performance. Here, we performed whole-genome sequencing of a native Chinese Lijiang pig (LJP) breed. By integrating previously published data, we explored the genetic structure and introgression of genetic components from commercial European pigs (EP) into the LJP, and examined the impact of this introgression on phenotypic traits., Results: Our analysis revealed significant introgression of EP breeds into the LJP and other domestic pig breeds in China. Using a haplotype-based approach, we quantified introgression levels and compared EP to LJP and other Chinese domestic pigs. The results show that EP introgression is widely prevalent in Chinese domestic pigs, although there are significant differences between breeds. We propose that LJP could potentially act as a mediator for the transmission of EP haplotypes. We also examined the correlation between EP introgression and the number of thoracic vertebrae in LJP and identified VRTN and STUM as candidate genes for this trait., Conclusions: Our study provides evidence of introgressed European haplotypes in the LJP breed and describes the potential role of EP introgression on phenotypic changes of this indigenous breed., (© 2024. The Author(s).)

Background: Academic emotion is a fundamental emotional concept closely linked to academic achievement. Understanding the connection between academic emotion and the personality trait of hardiness is pivotal in maintaining a stable career orientation throughout one's educational career. Therefore, in pursuit of fostering the robust growth of nursing careers, it is imperative to delve into the academic emotions experienced by undergraduate nursing students. This study endeavors to mitigate the impact of gender differences among nursing students while investigating the intricate relationship between academic emotions and the trait of hardiness in their personalities., Methods: This study employed a cross-sectional research design. We gathered data from a convenient sample of 292 nursing students enrolled at Shanxi University of Chinese Medicine. Each student provided demographic information and responded to a general academic mood questionnaire, as well as a Hardiness Personality Rating Scale. Subsequently, we used canonical correlation analysis to evaluate the correlation between academic emotion and tenacity personality in 292 undergraduate nursing students., Results: We discovered that academic emotions among nursing students are predominantly characterized by feelings of disappointment and boredom. Furthermore, personality hardiness is primarily influenced by the dimensions of engagement and control. It is important to note that a heightened level of negative, low-arousal academic emotions can diminish the level of engagement. The first typical correlation coefficient corresponding to academic emotion and hardiness were 0.660. The linear combination of standardized variables of the first typical variable corresponding to academic emotion (X1) = -0.444*negative hyperarousal -0.443 * positive hyperarousal + 0.694 * negative hypoarousal -0.260 * positive hypoarousal. The standardized variable equation of the first typical variable corresponding to hardiness personality (η1) = 0.235* hardiness -0.433* control -0.530* investment -0.303* challenge., Conclusions: Nursing students generally believe that their input is out of proportion to the return, and this unbalanced emotional experience will seriously affect their academic emotions in China. It is suggested that paying attention to cultivating their tenacious personality traits in the teaching process may help to enhance their academic emotions and enhance the sense of belonging and identity of nursing students engaged in the nursing profession., (© 2024. The Author(s).)

Objective: The aim of the study was to investigate the 3.0 Tesla magnetic resonance imaging (MRI) features of Madelung's deformity., Materials and Methods: The wrist MRI scans of 19 patients clinically diagnosed with Madelung's deformity and 20 patients without deformity were consecutively selected from Beijing Jishuitan Hospital between April 2019 and December 2022 for observation, in the case group and control group, respectively. Multiple linear regression was used to analyze the factors affecting tilting angle and width of central disc (CD, also termed as triangular fibrocartilage, the main component of triangular fibrocartilage complex), while the chi-square test was used to compare the occurrences of CD (radial) attachment displacement, VL, and RTL. p < 0.05 indicated statistical significance., Results: Madelung's deformity significantly contributed to the tilting and thickening of the CD. In the case group, the tilting angle and thickness of CD were (51.46 ± 1.33)° and (0.23 ± 0.01) cm, respectively, which was statistically significant (p < 0.05); the radial attachment of the CD significantly shifted away from the distal articular surface level (χ 2  = 39.00, p < 0.001), with a mean displacement of (0.97 ± 0.38) cm. Furthermore, the cases demonstrated abnormally developed Vickers ligament (χ 2  = 35.19, p < 0.001) and radiotriquetral ligament (χ 2  = 25.66, p < 0.001)., Conclusion: MRI provides a notable advantage in diagnosing Madelung's deformity. Compared with the control group, patients with Madelung's deformity exhibited tilting and thickening of the CD. Additionally, the radial attachment of the CD was significantly shifted proximally with abnormal development of Vickers and radiotriquetral ligaments., (© 2024. The Author(s).)

Background: Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms., Methods: A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD., Results: A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026-7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234-8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108-5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093-1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201-0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221-0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950-0.996) were less likely to have depressive symptoms., Conclusions: Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors., (© 2024. The Author(s).)

Background: Clinical guidelines recommend a preoperative forced expiratory volume in one second (FEV 1 ) of > 2 L as an indication for left or right pneumonectomy. This study compares the safety and long-term prognosis of pneumonectomy for destroyed lung (DL) patients with FEV 1  ≤ 2 L or > 2 L., Methods: A total of 123 DL patients who underwent pneumonectomy between November 2002 and February 2023 at the Department of Thoracic Surgery, Beijing Chest Hospital were included. Patients were sorted into two groups: the FEV 1  > 2 L group (n = 30) or the FEV 1  ≤ 2 L group (n = 96). Clinical characteristics and rates of mortality, complications within 30 days after surgery, long-term mortality, occurrence of residual lung infection/tuberculosis (TB), bronchopleural fistula/empyema, readmission by last follow-up visit, and modified Medical Research Council (mMRC) dyspnea scores were compared between groups., Results: A total of 96.7% (119/123) of patients were successfully discharged, with 75.6% (93/123) in the FEV 1  ≤ 2 L group. As compared to the FEV 1  > 2 L group, the FEV 1  ≤ 2 L group exhibited significantly lower proportions of males, patients with smoking histories, patients with lung cavities as revealed by chest imaging findings, and patients with lower forced vital capacity as a percentage of predicted values (FVC%pred) (P values of 0.001, 0.027, and 0.023, 0.003, respectively). No significant intergroup differences were observed in rates of mortality within 30 days after surgery, incidence of postoperative complications, long-term mortality, occurrence of residual lung infection/TB, bronchopleural fistula/empyema, mMRC ≥ 1 at the last follow-up visit, and postoperative readmission (P > 0.05)., Conclusions: As most DL patients planning to undergo left/right pneumonectomy have a preoperative FEV 1  ≤ 2 L, the procedure is generally safe with favourable short- and long-term prognoses for these patients. Consequently, the results of this study suggest that DL patient preoperative FEV 1  > 2 L should not be utilised as an exclusion criterion for pneumonectomy., (© 2024. The Author(s).)

Introduction: Studies have revealed that age is associated with the risk of lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC). This study aimed to identify the optimal cut point of age for a more precise prediction model of LLNM and to reveal differences in risk factors between patients of distinct age stages., Methods: A total of 499 patients who had undergone thyroidectomy and lateral neck dissection (LND) for PTC were enrolled. The locally weighted scatterplot smoothing (LOWESS) curve and the 'changepoint' package were used to identify the optimal age cut point using R. Multivariate logistic regression analysis was performed to identify independent risk factors of LLNM in each group divided by age., Results: Younger patients were more likely to have LLNM, and the optimal cut points of age to stratify the risk of LLNM were 30 and 45 years old. Central lymph node metastasis (CLNM) was a prominent risk factor for further LNM in all patients. Apart from CLNM, sex(p = 0.033), tumor size(p = 0.027), and tumor location(p = 0.020) were independent predictors for patients younger than 30 years old; tumor location(p = 0.013), extra-thyroidal extension(p < 0.001), and extra-nodal extension(p = 0.042) were independent risk factors for patients older than 45 years old., Conclusions: Our study could be interpreted as an implication for a change in surgical management. LND should be more actively performed when CLNM is confirmed; for younger patients with tumors in the upper lobe and older patients with extra-thyroidal extension tumors, more aggressive detection of the lateral neck might be considered., (© 2024. The Author(s).)

Background and Purpose: Whether symptomatic unruptured intracranial aneurysms (UIAs) lead to change in circulating inflammation remains unclear. This study aims to evaluate the role of hematological inflammatory indicators in predicting symptomatic UIA., Methods: Adult patients diagnosed with saccular intracranial aneurysm from March 2019 to September 2023 were recruited retrospectively. Clinical and laboratory data, including the white blood cells (WBC), neutral counts (NEUT), lymphocyte counts (LYM), and monocyte counts (MONO) of each patient, were collected. The neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were calculated as NLR = NEUT/LYM, LMR = LYM/MONO, SII = PLT*NEUT/LYM. The hematological inflammatory indicators were compared in symptomatic saccular and asymptomatic UIA patients. Multivariable logistic regression analyses were performed to explore the factors predicting symptomatic UIA., Results: One hundred and fifty UIA patients with a mean age of 58.5 ± 12.4 were included, of which 68% were females. The NLR and LMR were significantly associated with symptomatic UIA, and the association remained in small UIAs (< 7 mm). The multiple logistic regression analysis showed that NLR was independently associated with symptomatic UIA. On ROC curve analysis, the optimal cutoff value of NLR to differentiate symptomatic from asymptomatic was 2.38. In addition, LMR was significantly associated with symptomatic UIA smaller than 7 mm., Conclusion: There was a significant correlation between NLR and symptomatic UIA. The NLR was independently associated with symptomatic UIA., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Tandem C2 domains, nuclear (TC2N) is a C2 domain-containing protein that belongs to the carboxyl-terminal type (C-type) tandem C2 protein family, and acts as an oncogenic driver in several cancers. Previously, we preliminarily reported that TC2N mediates the PI3K-Akt signaling pathway to inhibit tumor growth of breast cancer (BC) cells. Beyond that, its precise biological functions and detailed molecular mechanisms in BC development and progression are not fully understood., Methods: Tumor tissues of 212 BC patients were subjected to tissue microarray and further assessed the associations of TC2N expression with pathological parameters and FASN expression. The protein levels of TC2N and FASN in cell lines and tumor specimens were monitored by qRT-PCR, WB, immunofluorescence and immunohistochemistry. In vitro cell assays, in vivo nude mice model was used to assess the effect of TC2N ectopic expression on tumor metastasis and stemness of breast cancer cells. The downstream signaling pathway or target molecule of TC2N was mined using a combination of transcriptomics, proteomics and lipidomics, and the underlying mechanism was explored by WB and co-IP assays., Results: Here, we found that the expression of TC2N remarkedly silenced in metastatic and poorly differentiated tumors. Function-wide, TC2N strongly inhibits tumor metastasis and stem-like properties of BC via inhibition of fatty acid synthesis. Mechanism-wise, TC2N blocks neddylated PTEN-mediated FASN stabilization by a dual mechanism. The C2B domain is crucial for nuclear localization of TC2N, further consolidating the TRIM21-mediated ubiquitylation and degradation of FASN by competing with neddylated PTEN for binding to FASN in nucleus. On the other hand, cytoplasmic TC2N interacts with import proteins, thereby restraining nuclear import of PTEN to decrease neddylated PTEN level., Conclusions: Altogether, we demonstrate a previously unidentified role and mechanism of TC2N in regulation of lipid metabolism and PTEN neddylation, providing a potential therapeutic target for anti-cancer., (© 2023. The Author(s).)

Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting., (© 2023. The Author(s).)

Background: Gliomas, a prevalent form of primary brain tumors, are linked with a high mortality rate and unfavorable prognoses. Disulfidptosis, an innovative form of programmed cell death, has received scant attention concerning disulfidptosis-related lncRNAs (DRLs). The objective of this investigation was to ascertain a prognostic signature utilizing DRLs to forecast the prognosis and treatment targets of glioma patients., Methods: RNA-seq data were procured from The Cancer Genome Atlas database. Disulfidptosis-related genes were compiled from prior research. An analysis of multivariate Cox regression and the least absolute selection operator was used to construct a risk model using six DRLs. The risk signature's performance was evaluated via Kaplan-Meier survival curves and receiver operating characteristic curves. Additionally, functional analysis was carried out using GO, KEGG, and single-sample GSEA to investigate the biological functions and immune infiltration. The research also evaluated tumor mutational burden, therapeutic drug sensitivity, and consensus cluster analysis. Reverse transcription quantitative PCR was conducted to validate the expression level of DRLs., Results: A prognostic signature comprising six DRLs was developed to predict the prognosis of glioma patients. High-risk patients had significantly shorter overall survival than low-risk patients. The robustness of the risk model was validated by receiver operating characteristic curves and subgroup survival analysis. Risk model was used independently as a prognostic indicator for the glioma patients. Notably, the low-risk patients displayed a substantial decrease in the immune checkpoints, the proportion of immune cells, ESTIMATE and immune score. IC50 values from the different risk groups allowed us to discern three drugs for the treatment of glioma patients. Lastly, the potential clinical significance of six DRLs was determined., Conclusions: A novel six DRLs signature was developed to predict prognosis and may provide valuable insights for patients with glioma seeking novel immunotherapy and targeted therapy., (© 2023. The Author(s).)

Background: Prolonged length of stay in post-anesthesia care unit (PLOS in PACU) is a combination of risk factors and complications that can compromise quality of care and operating room efficiency. Our study aimed to develop a nomogram to predict PLOS in PACU of patients undergoing elective surgery., Methods: Data from 24017 patients were collected. Least absolute shrinkage and selection operator (LASSO) was used to screen variables. A logistic regression model was built on variables determined by a combined method of forward selection and backward elimination. Nomogram was designed with the model. The nomogram performance was evaluated with the area under the receiver operating characteristic curve (AUC) for discrimination, calibration plot for consistency between predictions and actuality, and decision curve analysis (DCA) for clinical application value., Results: A nomogram was established based on the selected ten variables, including age, BMI < 21 kg/m 2 , American society of Anesthesiologists Physical Status (ASA), surgery type, chill, delirium, pain, naloxone, operation duration and blood transfusion. The C-index value was 0.773 [95% confidence interval (CI) = 0.765 - 0.781] in the development set and 0.757 (95% CI = 0.744-0.770) in the validation set. The AUC was > 0.75 for the prediction of PLOS in PACU. The calibration curves revealed high consistencies between the predicted and actual probability. The DCA showed that if the threshold probability is over 10% , using the models to predict PLOS in PACU and implement intervention adds more benefit., Conclusions: This study presented a nomogram to facilitate individualized prediction of PLOS in PACU for patients undergoing elective surgery., (© 2023. The Author(s).)

Background: The postponement of parenthood is a global public health issue that has received attention of many public health experts. However, few studies have investigated the postponement in marriage age, marriage and conception interval, and pregnancy age in terms of demographic and regional heterogenicities., Methods: This is a cross-sectional, registry-based study, and a total of 13 894 601 nulliparous couples who participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013-2019 were included. We calculated annual percentage change and forest plots for marriage age, marriage and conception interval, and pregnancy age., Results: Late marriage (marriage age ≥ 35 years), long marriage and conception interval (marriage and conception interval ≥ 2 years), and advanced pregnancy (pregnancy age ≥ 35 years) increased from 1.20%, 22.01%, and 1.88% in 2013 to 1.69%, 32.75%, and 2.79% in 2019, respectively. The corresponding annual percentage changes were 6.55%, 8.44%, and 8.17%. Participants without higher education had a higher annual percentage change, but comparable prevalence for long marriage and conception interval with participants with higher education. Participants residing in second- or new first-tier cities, and the northeast of China who had a higher prevalence of parenthood postponement also had higher corresponding annual percentage changes., Conclusions: Structural postponement of parenthood with demographic and regional heterogenicities was observed among Chinese nulliparous couples with planned pregnancies during 2013-2019. Inclusive and comprehensive parenting support should be developed and implemented in mainland China to minimize the negative health effects arising from the postponement, especially for couples without higher education and living in new first/second-tier cities or the northeast China., (© 2023. The Author(s).)

Background: Most studies initiated basal-bolus insulin in a ratio of 1:1 and titrated based on glucose. This study aimed to investigate the effectiveness and safety of a weight-based and ratio of 1:1.5 basal-bolus insulin using an algorithm for both initiation and titration in hospitalized patients with type 2 diabetes (T2D)., Methods: Hospitalized patients with T2D were randomly assigned to two groups in equal numbers to receive 1:1.5 and 1:1 ratios of basal-bolus insulin using a weight-based algorithm for both initiation and titration. The primary outcome was the time taken to reach the fasting blood glucose (FBG) target and 2-h postprandial blood glucose (2hBG) targets after three meals. The secondary outcome included insulin dosage to achieve glycemic control and the incidence of hypoglycemia during hospitalization., Results: 250 patients were screened between October 2021 and June 2022, 220 were randomly grouped, and 182 completed the trial (89 in the 1:1.5 and 93 in the 1:1 groups). The time taken to reach FBG targets was comparable between the two groups (3.4 ± 1.7 vs. 3.0 ± 1.3 days, p = 0.137) within about 3 days. The 2hBG after three meals was shorter in the 1:1.5 group than in the 1:1group (2.9 ± 1.5 vs. 3.4 ± 1.4 days, p = 0.015 for breakfast, 3.0 ± 1.6 vs. 3.6 ± 1.4 days, p = 0.005 for lunch, and 3.1 ± 2.1 vs. 4.0 ± 1.5 days, p = 0.002 for dinner). No significant difference in insulin dosages was found between the two groups at the end of the study. The incidence of hypoglycemia was similar in both groups., Conclusions: We demonstrated that fixed dose-ratio basal-bolus insulin at 1:1.5 calculated using a weight-based initiation and titration algorithm was simple, as effective, and safe as ratio at 1:1 in managing T2D in hospitalized patients. Trial Registration ChiCTR 2,100,050,963. Date of registration: September 8, 2021., (© 2023. The Author(s).)

Background and Aim: Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy., Methods: A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses., Results: In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8 + T (P = 0.003), CD4 + T CM (P = 0.033), CD4 + T EM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4 + T CM (P = 0.010), CD4 + T EM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients., Conclusions: Changes in effector CD8 + T cells, effector and memory CD4 + T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies., (© 2023. The Author(s).)

Background: To develop and validate a conventional MRI-based radiomic model for predicting prognosis in patients with IDH wild-type glioblastoma (GBM) and reveal the biological underpinning of the radiomic phenotypes., Methods: A total of 801 adult patients (training set, N = 471; internal validation set, N = 239; external validation set, N = 91) diagnosed with IDH wild-type GBM were included. A 20-feature radiomic risk score (Radscore) was built for overall survival (OS) prediction by univariate prognostic analysis and least absolute shrinkage and selection operator (LASSO) Cox regression in the training set. GSEA and WGCNA were applied to identify the intersectional pathways underlying the prognostic radiomic features in a radiogenomic analysis set with paired MRI and RNA-seq data (N = 132). The biological meaning of the conventional MRI sequences was revealed using a Mantel test., Results: Radscore was demonstrated to be an independent prognostic factor (P < 0.001). Incorporating the Radscore into a clinical model resulted in a radiomic-clinical nomogram predicting survival better than either the Radscore model or the clinical model alone, with better calibration and classification accuracy (a total net reclassification improvement of 0.403, P < 0.001). Three pathway categories (proliferation, DNA damage response, and immune response) were significantly correlated with the prognostic radiomic phenotypes., Conclusion: Our findings indicated that the prognostic radiomic phenotypes derived from conventional MRI are driven by distinct pathways involved in proliferation, DNA damage response, and immunity of IDH wild-type GBM., (© 2023. The Author(s).)

Background: Multiple studies have indicated an association between red and processed meat consumption and the incidence of ischemic heart disease (IHD). In this study, we aimed to assess the burden of IHD caused by a diet high in red and processed meat in 204 countries and territories between 1990 and 2019, using data from the Global Burden of Disease (GBD) 2019., Methods: We extracted data from the GBD 2019, which included the number of deaths, age-standardized mortality rates (ASMR), disability-adjusted life years (DALYs), and age-standardized DALYs rates (ASDR) attributed to IHD caused by a diet high in red and processed meat. We then calculated the burden of IHD attributable to a high intake of red and processed meat in each country and territory, stratified by age, sex, and socio-demographic index (SDI)., Results: Globally, a high intake of red meat was responsible for 351,200 (95% uncertainty interval (UI): 559,000-642,700) deaths from IHD in 2019, while a high intake of processed meat was associated with 171,700 (95% UI: 30,100-320,000) deaths from IHD. Between 1990 and 2019, while the corresponding age-standardized rates declined, the numbers of deaths and DALYs increased. China had the highest number of deaths [98,386.9 (95% UI: 14,999.3-189,812.7)] caused by a high intake of red meat, while United States of America [33,129.6 (95% UI: 7,150-59,593.8)] was associated with the highest number of deaths caused by high intake of processed meat for IHD in 2019. Males experienced a greater burden of IHD caused by a high intake of red and processed meat than females. The ASMR and ASDR of IHD attributed to a high intake of red meat decreased in countries with high SDI, high-middle SDI and low SDI, while the ASMR and ASDR of IHD attributed to a high intake of processed meat decreased only in countries with high SDI and high-middle SDI., Conclusion: Although there is a decline in the ASMR and ASDR of IHD caused by a high intake of red and processed meat, there is also an increase in deaths and DALYs number globally. Additionally, there is a heterogeneous burden of IHD related to a high intake of red and processed meat across regions and countries, with males experiencing a greater burden than females. Implementing targeted policies and interventions is required to reduce the burden of IHD caused by a high intake of red and processed meat., (© 2023. The Author(s).)

Background: RAD51B plays a significant role in homologous recombination-mediated repair of DNA double-strand breaks. Many enhancer variants are involved in cancer development and progression. However, the significance of enhancer variants of RAD51B in glioma susceptibility and progression remains unclear., Methods: A case-control study consisting of 1056 individuals was conducted to evaluate the associations of enhancer variants of RAD51B with glioma susceptibility and progression. Sequenom MassARRAY technology was used for genotyping. The function of enhancer variants was explored by biochemical assays., Results: A significantly decreased risk of glioma was associated with rs6573816 GC genotype compared with rs6573816 GG genotype (OR = 0.66, 95% CI 0.45-0.97; P = 0.034). Multivariable Cox regression revealed that rs6573816 was significantly associated with glioma progression in a sex-dependent manner. Worse PFS was found in the male patients with high grade glioma carrying rs6573816 GC or CC genotype (HR = 2.28, 95% CI 1.14-4.57; P = 0.020). The rs6573816 C allele repressed enhancer activity by affecting transcription factor POU2F1 binding, which resulted in lower expression of RAD51B. Remarkably attenuated expression of RAD51B was observed following POU2F1 knockdown. Consistently, positive correlation between the expression of POU2F1 and RAD51B was found in lymphoblastic cells and glioma tissues., Conclusions: These results indicate that an enhancer variant of RAD51B rs6573816 influences enhancer activity by changing a POU2F1 binding site and confers susceptibility and progression to glioma., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM., Methods: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded., Results: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group., Conclusions: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM., Trial Registration: ClinicalTrail.gov NCT05782192., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: We aimed to develop machine learning models for prediction of molecular subgroups (low-risk group and intermediate/high-risk group) and molecular marker (KIAA1549-BRAF fusion) of pediatric low-grade gliomas (PLGGs) based on radiomic features extracted from multiparametric MRI., Methods: 61 patients with PLGGs were included in this retrospective study, which were divided into a training set and an internal validation set at a ratio of 2:1 based on the molecular subgroups or the molecular marker. The patients were classified into low-risk and intermediate/high-risk groups, BRAF fusion positive and negative groups, respectively. We extracted 5929 radiomic features from multiparametric MRI. Thereafter, we removed redundant features, trained random forest models on the training set for predicting the molecular subgroups or the molecular marker, and validated their performance on the internal validation set. The performance of the prediction model was verified by 3-fold cross-validation., Results: We constructed the classification model differentiating low-risk PLGGs from intermediate/high-risk PLGGs using 4 relevant features, with an AUC of 0.833 and an accuracy of 76.2% in the internal validation set. In the prediction model for predicting KIAA1549-BRAF fusion using 4 relevant features, an AUC of 0.818 and an accuracy of 81.0% were achieved in the internal validation set., Conclusions: The current study demonstrates that MRI radiomics is able to predict molecular subgroups of PLGGs and KIAA1549-BRAF fusion with satisfying sensitivity., Trial Registration: This study was retrospectively registered at clinicaltrials.gov (NCT04217018)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The knowledge, attitude, and practice (KAP) of Chinese patients with allergic rhinitis (AR) on AR is poorly known. This study investigated the KAP towards AR in patients with this disease and explored the factors associated with KAP., Methods: This cross-sectional study enrolled patients with AR in Zhangjiagang Hospital of Traditional Chinese Medicine between October 2022 and March 2023., Results: This study included 656 valid questionnaires. Most participants were 26-35 years old (36.13%) and were female (55.18%). The knowledge, attitude, and practice scores were 5.70 ± 2.88 (possible range: 0-12), 29.51 ± 3.52 (possible range: 9-45), and 34.13 ± 7.55 (possible range: 9-45), indicating poor knowledge, unfavorable attitudes, and proactive practice. AR history of 3-5 years (adjusted odds ratio (adjOR) = 1.62, 95% confidence interval (CI): 1.03-2.54, P = 0.037), AR history of > 6 years (adjOR = 1.64, 95%CI: 1.06-2.54, P = 0.027), and know their own allergens (adjOR = 2.34, 95%CI: 1.28-4.25, P = 0.005) were independently associated with the sufficient knowledge. AR history of ≥ 6 years (adjOR = 0.60, 95%CI: 0.37-0.96, P = 0.035), and liking sports (adjOR = 1.58, 95%CI = 1.07-2.33, P = 0.020) were independently associated with the positive attitude. The knowledge scores (adjOR = 1.14, 95%CI: 1.05-1.22, P = 0.001), attitude scores (adjOR = 1.24, 95%CI: 1.17-1.32, P < 0.001), age 36-45 (adjOR = 2.13, 95%CI: 1.19-3.82, P = 0.011), employed (adjOR = 0.59, 95%CI: 0.37-0.94, P = 0.026), and liking sports (adjOR = 2.11, 95%CI: 1.43-3.14, P < 0.001) were independently associated with the proactive practice., Conclusions: Patients with AR have poor knowledge and unfavorable attitudes but good practice toward AR. Continuous quality teaching interventions and education on patients for AR were recommended., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: There are many studies indicating that alterations in the abundance of certain gut microbiota are associated with colorectal cancer (CRC). However, a causal relationship has not been identified due to confounding factors such as lifestyle, environmental, and possible reverse causal associations between the two. Furthermore, certain host gene mutations can also contribute to the development of CRC. However, the association between genes and gut microbes in patients with CRC has not been extensively studied., Methods: We conducted a two-sample Mendelian randomization (MR) study to reveal the causal relationship between gut microbiota and CRC. We obtained SNPs associated with gut microbiome abundance as instrumental variables (IVs) from a large-scale, multi-ethnic GWAS study, and extracted CRC-related datasets from an East Asian Population genetic consortia GWAS (AGWAS) study and FinnGen consortium, respectively. We analyzed a total of 166 bacterial features at four taxonomic levels, including order, family, genus, and species. The inverse-variance-weighted (IVW), weighted median, MR-Egger, and simple median methods were applied to the MR analysis, and the robustness of the results were tested using a series of sensitivity analyses. We extracted IVs of gut microbiota with direct causal association with CRC for SNP annotation to identify the genes in which these genetic variants were located to reveal the possible host gene-microbiome associations in CRC patients., Results: The findings from our MR analysis based on CRC-associated GWAS datasets from AGWAS revealed causal relationships between 6 bacterial taxa and CRC at a locus-wide significance level (P < 1 × 10 -5 ). The IVW method found that family Porphyromonadaceae, genera Anaerotruncus, Intestinibacter, Slackia, and Ruminococcaceae UCG004, and species Eubacterium coprostanoligenes group were positively associated with CRC risk, which was generally consistent with the results of other complementary analyses. The results of a meta-analysis of the MR estimates from the AGWAS and the FinnGen datasets showed that family Porphyromonadaceae and genera Slackia, Anaerotruncus, and Intestinibacter replicated the same causal association. Sensitivity analysis of all causal associations did not indicate significant heterogeneity, horizontal pleiotropy, or reverse causal associations. We annotated the SNPs at a locus-wide significance level of the above intestinal flora and identified 24 host genes that may be related to pathogenic intestinal microflora in CRC patients., Conclusion: This study supported the causal relationship of gut microbiota on CRC and revealed a possible correlation between genes and pathogenic microbiota in CRC. These findings suggested that the study of the gut microbiome and its further multi-omics analysis was important for the prevention and treatment of CRC., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: Pulmonary sarcomatoid carcinoma (PSC) is a rare histological type of non-small cell lung cancer (NSCLC). There are no specific treatment guidelines for PSC. For advanced PSC (stage II-IV), the role of chemotherapy is still controversial. The purpose of this study was to investigate the effect of chemotherapy on the prognosis of advanced PSC., Methods: A total of 960 patients with advanced PSC from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2019 were enrolled in this study. To investigate the prognostic factors, the Cox proportional hazard regression model was conducted. A total of 642 cases were obtained after propensity score matching (PSM). The Kaplan‒Meier method was applied to compare overall survival (OS) and cancer-specific survival (CSS)., Results: For all 960 cases included in this study, the Cox proportional hazard model was applied for prognostic analysis. Univariate and multivariate analyses showed that stage, T stage, N stage, M stage, surgery, and chemotherapy were prognostic factors for OS and CSS (P < 0.05). A total of 642 cases were obtained after PSM, with no significant difference between the two groups for all variables. Kaplan‒Meier curves indicated that for OS and CSS, the prognosis was significantly better in the chemotherapy group than in the no-chemotherapy group., Conclusions: For advanced PSC, chemotherapy can significantly improve the OS and CSS of patients. Chemotherapy should be an important part of PSC treatment., (© 2023. The Author(s).)

Aim: To explore the genetic effects of CYP2C8, CYP2C9, CYP2J2, and EPHX2, the key genes involved in epoxyeicosatrienoic acid processing and degradation pathways in gestational diabetes mellitus (GDM) and metabolic traits in Chinese pregnant women., Methods: A total of 2548 unrelated pregnant women were included, of which 938 had GDM and 1610 were considered as controls. Common variants were genotyped using the Infinium Asian Screening Array. Association studies of single nucleotide polymorphisms (SNPs) with GDM and related traits were performed using logistic regression and multivariable linear regression analyses. A genetic risk score (GRS) model based on 12 independent target SNPs associated with GDM was constructed. Logistic regression was used to estimate odds ratios and 95% confidence intervals, adjusting for potential confounders including age, pre-pregnancy body mass index, history of polycystic ovarian syndrome, history of GDM, and family history of diabetes, with GRS entered both as a continuous variable and categorized groups. The relationship between GRS and quantitative traits was also evaluated., Results: The 12 SNPs in CYP2C8, CYP2C9, CYP2J2, and EPHX2 were significantly associated with GDM after adjusting for covariates (all P < 0.05). The GRS generated from these SNPs significantly correlated with GDM. Furthermore, a significant interaction between CYP2J2 and CYP2C8 in GDM (P Interaction = 0.014, OR Interaction = 0.61, 95%CI 0.41-0.90) was observed., Conclusion: We found significant associations between GDM susceptibility and 12 SNPs of the four genes involved in epoxyeicosatrienoic acid processing and degradation pathways in a Chinese population. Subjects with a higher GRS showed higher GDM susceptibility with higher fasting plasma glucose and area under the curve of glucose and poorer β-cell function., (© 2023. The Author(s).)

By 31 May 2022, original/Alpha, Delta and Omicron strains induced 101 outbreaks of COVID-19 in mainland China. Most outbreaks were cleared by combining non-pharmaceutical interventions (NPIs) with vaccines, but continuous virus variations challenged the dynamic zero-case policy (DZCP), posing questions of what are the prerequisites and threshold levels for success? And what are the independent effects of vaccination in each outbreak? Using a modified classic infectious disease dynamic model and an iterative relationship for new infections per day, the effectiveness of vaccines and NPIs was deduced, from which the independent effectiveness of vaccines was derived. There was a negative correlation between vaccination coverage rates and virus transmission. For the Delta strain, a 61.8% increase in the vaccination rate (VR) reduced the control reproduction number (CRN) by about 27%. For the Omicron strain, a 20.43% increase in VR, including booster shots, reduced the CRN by 42.16%. The implementation speed of NPIs against the original/Alpha strain was faster than the virus's transmission speed, and vaccines significantly accelerated the DZCP against the Delta strain. The CRN ([Formula: see text]) during the exponential growth phase and the peak time and intensity of NPIs were key factors affecting a comprehensive theoretical threshold condition for DZCP success, illustrated by contour diagrams for the CRN under different conditions. The DZCP maintained the [Formula: see text] of 101 outbreaks below the safe threshold level, but the strength of NPIs was close to saturation especially for Omicron, and there was little room for improvement. Only by curbing the rise in the early stage and shortening the exponential growth period could clearing be achieved quickly. Strengthening China's vaccine immune barrier can improve China's ability to prevent and control epidemics and provide greater scope for the selection and adjustment of NPIs. Otherwise, there will be rapid rises in infection rates and an extremely high peak and huge pressure on the healthcare system, and a potential increase in excess mortality., (© 2023. The Author(s).)

Background: The aim of this study was to determine the epidemiological pattern of maxillofacial fractures in northwestern China by retrospectively analysing the demographics, aetiologies, concomitant injuries, fracture sites, and management., Methods: A 10-year retrospective analysis of 2240 patients with maxillofacial fractures admitted to the General Hospital of Ningxia Medical University was conducted. The extracted data included sex, age, aetiology, fracture site, concomitant injuries, time of treatment, therapeutic approaches and complications. Statistical analyses were performed, including descriptive analysis and the chi-square test. Logistic regression was used to determine the impact factors of maxillofacial fractures and concomitant injuries. P values < 0.05 were considered statistically significant., Results: The age of the included patients ranged from 1 to 85 years, and the mean age was 35.88 ± 15.69 years. The male-to-female ratio was 3.9:1. The most frequent aetiology of maxillofacial fractures was road traffic accidents (RTAs) (56.3%), and the most common fracture sites were the anterior wall of the maxillary sinus, arcus zygomaticus and mandibular body. A total of 1147 patients (51.2%) were affected by concomitant injuries, with craniocerebral injury being the most common. Logistic regression analyses revealed increased risks of mid-facial fractures in elderly individuals (odds ratio (OR) = 1.029, P < 0.001) and females (OR = 0.719, P = 0.005). Younger patients had a higher risk of mandibular fractures (OR = 0.973, P < 0.001). RTAs increased the risk for mid-facial fractures and high falls increased the risk for mandibular fractures., Conclusions: The maxillofacial fracture pattern is correlated with sex, age and aetiology. Patients were mainly young and middle-aged males, and the main cause of injury was RTAs, mostly causing compound fractures. Medical staff must be systematically educated to comprehensively examine patients with injuries resulting from RTAs. The management of patients with fractures requires thorough consideration of the patient's age, aetiology, fracture site, and concomitant injuries., (© 2023. The Author(s).)

Diabetic cardiomyopathy (DCM) is a serious cardiovascular complication and the leading cause of death in diabetic patients. Patients typically do not experience any symptoms and have normal systolic and diastolic cardiac functions in the early stages of DCM. Because the majority of cardiac tissue has already been destroyed by the time DCM is detected, research must be conducted on biomarkers for early DCM, early diagnosis of DCM patients, and early symptomatic management to minimize mortality rates among DCM patients. Most of the existing implemented clinical markers are not very specific for DCM, especially in the early stages of DCM. Recent studies have shown that a number of new novel markers, such as galactin-3 (Gal-3), adiponectin (APN), and irisin, have significant changes in the clinical course of the various stages of DCM, suggesting that we may have a positive effect on the identification of DCM. As a summary of the current state of knowledge regarding DCM biomarkers, this review aims to inspire new ideas for identifying clinical markers and related pathophysiologic mechanisms that could be used in the early diagnosis and treatment of DCM., (© 2023. The Author(s).)

Background: Glioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma., Methods: Gene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal-Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan-Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman's rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels., Results: We found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment., Conclusion: These findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma., (© 2023. The Author(s).)

Background: Shortage of health professionals is one of the most important barriers for community health centers to provide quality primary care for chronic disease patients especially after the outbreak of COVID-19. Under such condition, medical students have been well-accepted as a force multiplier for community-based health service. Community service learning (CSL) based on medical student-led community health education service to support chronic disease self-management might be a valuable interactive learning tool in medical education. This study compared the attitudes toward medical student-led community health education service to support chronic disease self-management among three stakeholder roles in CSL, including medical students, faculty and patients., Methods: This cross-sectional comparative survey was conducted using a self-developed questionnaire among the convenience samples of undergraduate students and faculty members from the Medical College, Wuhan University of Science and Technology, as well as patient volunteers with chronic diseases recruited from a free on-site clinic offered by a community health center. Attitudes toward medical student-led community health education service to support chronic disease self-management were compared among students, faculty and patients., Results: A total of 515 valid questionnaires were obtained (342 were collected from medical students, 54 from faculty respondents, and 119 from patients). Overall positive attitudes toward medical student-led community health education service to support chronic disease self-management were positive. Among the three stakeholder roles, faculty and patients were more supportive of the current inadequate level of primary care provision within the community. However, patient respondents showed more negative attitudes towards using resources in higher medical education system to provide support for primary care practice, and participating in the medical student-led community health education service to support chronic disease self-management, and were most skeptical about the medical students' competency in supporting chronic disease self-management with their professional knowledge and skills. The educational value of CSL for medical undergraduates and the role of faculty instructors were most appreciated by faculty respondents. Additionally, > 62 years old and > 2 kinds of chronic diseases per patient exhibited significant correlations with positive patients' attitudes., Conclusions: Medical students, faculty and patients had overall positive attitudes towards CSL based on medical student-led community health education service to support chronic disease self-management. However, more should be done to create higher expectations and enthusiasm of patients about CSL., (© 2023. The Author(s).)