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Background: Tyrosine Kinase Inhibitors (TKIs) is an important therapy for patients with oncogene-mutated Non-Small Cell Lung Cancer (NSCLC). However, acquired resistance remains a major challenge. The efficacy of TKIs plus thoracic radiotherapy (RT) in oncogene-mutated NSCLC patients is uncertain. Therefore, we performed a meta-analysis to comprehensively evaluate the efficacy and safety of thoracic RT plus TKIs in oncogene-mutated NSCLC patients., Methods: The following databases were searched for relevant studies: PubMed, EMBASE, and Cochrane Library. Studies comparing the efficacy and safety of TKIs plus RT with TKIs alone in oncogene-mutated NSCLC patients were included in this analysis. Outcomes were median progression-free survival (mPFS), median overall survival (mOS), and incidence of adverse events (AEs). This analysis performed a subgroup analysis of the efficacy of first-line TKIs in combination with RT., Results: This meta-analysis included 12 studies with 2936 patients (n = 823 patients with TKIs plus thoracic RT, n = 2113 patients with TKIs alone). The results showed that patients who received treatment with TKIs plus thoracic RT were associated with superior mPFS and mOS than those who were treated with TKIs alone (hazard ratio [HR]: 0.42, 95% CI 0.30-0.59, p < 0.00001; HR: 0.56, 95% CI 0.41-0.70, p < 0.00001, respectively). Subgroup analyses showed that TKIs plus thoracic RT as first-line treatment was associated with better mPFS and OS (HR: 0.37, 95% CI 0.26-0.52, p < 0.00001; HR: 0.47, 95% CI 0.31-0.70, p = 0.0002, respectively). Although the combination of TKIs with thoracic RT was associated with an increased risk of total AEs (odds ratio [OR]: 1.17, 95% CI 1.06-1.29, P = 0.002), there was no significant difference in serious AEs (grade ≥ 3) (OR: 1.06, 95% CI 0.58-1.92, P = 0.86). The most frequently occurring radiation-related AEs were radiation pneumonitis, radiation esophagitis, and radiation dermatitis, with overall rates of 41.3%, 15.4%, and 11.1%, respectively. The incidence of severe radiation pneumonitis and radiation esophagitis was 4.5% and 6.2%, respectively., Conclusions: In comparison to TKIs alone, TKIs plus thoracic RT are associated with survival benefits, especially as a first-line treatment option. Although TKIs plus thoracic RT may increase the risk of total AEs, it did not increase the risk of severe AEs. Therefore, TKIs plus thoracic RT may be a promising therapeutic regimen for oncogene-mutated NSCLC patients., (© 2024. The Author(s).)

Background: Trihliex transcription factors (TFs) play crucial roles in plant growth and development, stress response, and plant hormone signaling network transmission. In order to comprehensively investigate the functions of trihliex genes in eggplant development and the abiotic stress response, we conducted an extensive analysis of the trihliex gene family in the eggplant genome., Results: In this study, 30 trihelix gene family members were unevenly distributed on 12 chromosomes. On the basis of their phylogenetic relationships, these genes were conserved in different plant species and could be divided into six subfamilies, with trihelix genes within the same subfamily sharing similar structures. The promoter regions of trihelix genes contained cis-acting elements related to plant growth and development, plant hormones, and abiotic stress responses, suggesting potential applications in the development of more resistant crops. Selective pressure assessments indicated that trihliex genes have undergone purifying selection pressure. Expression analysis on the basis of transcriptomic profiles revealed that SmGT18, SmGT29, SmGT6, and SmGT28 are highly expressed in roots, leaves, flowers, and fruits, respectively. Expression analysis via quantitative real-time PCR (qRT‒PCR) revealed that most trihelix genes respond to low temperature, abscisic acid (ABA), and salicylic acid (SA), with SmGT29 exhibiting significant upregulation under cold stress conditions. The SmGT29 gene was subsequently successfully cloned from eggplant, which was located in the nucleus, robust transcriptional activity, and a protein molecular weight of 74.59 kDa. On the basis of these findings, SmGT29 was postulated to be a pivotal candidate gene that actively responds to biotic stress stimuli, thereby supporting the plant's innate stress resistance mechanisms., Conclusion: In summary, this study was the first report on trihelix genes and their potential roles in eggplant plants. These results provided valuable insights for enhancing stress resistance and quality traits in eggplant breeding, thereby serving as a crucial reference for future improvement efforts., (© 2024. The Author(s).)

Background: Gram-negative bacteria are the main bacterial pathogens infecting Chinese giant salamanders (Andrias davidianus; CGS) in captivity and the wild, causing substantial economic losses in the CGS industry. However, the molecular mechanisms underlying pathogenesis following infection remain unclear., Results: Spleen-derived macrophages from healthy CGS were isolated, cultured, and identified using density gradient centrifugation and immunofluorescence. A macrophage transcriptome database was established 0, 6, and 12 h post lipopolysaccharide stimulation using RNA-sequencing. In the final database 76,743 unigenes and 4,698 differentially expressed genes (DEGs) were functionally annotated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results showed that DEGs were concentrated in toll-like receptor-nuclear factor kappa B-related immune pathways. Ten DEGs were validated 12 h after lipopolysaccharide (LPS) stimulation. Although the common LPS recognition receptor toll-like receptor 4 was not activated and the key adaptor protein MyD88 showed no significant response, we observed significant up-regulation of the following adaptors: toll/interleukin-1 receptor domain-containing adaptor inducing interferon-β, tumour necrosis factor receptor-associated factor 6, and transforming growth factor-β activated kinase 1, which are located downstream of the non-classical MyD88 pathway., Conclusions: In contrast to that in other species, macrophage activation in CGS could depend on the non-classical MyD88 pathway in response to bacterial infection. Our study provides insights into the molecular mechanisms regulating CGS antibacterial responses, with implications for disease prevention and understanding immune evolution in amphibians., (© 2024. The Author(s).)

The blood-brain barrier (BBB) is a critical interface that maintains the central nervous system homeostasis by controlling the exchange of substances between the blood and the brain. Disruption of the BBB plays a vital role in the development of neuroinflammation and neurological dysfunction in sepsis, but the mechanisms by which the BBB becomes disrupted during sepsis are not well understood. Here, we induced endotoxemia, a major type of sepsis, in mice by intraperitoneal injection of lipopolysaccharide (LPS). LPS acutely increased BBB permeability, activated microglia, and heightened inflammatory responses in brain endothelium and parenchyma. Concurrently, LPS or proinflammatory cytokines activated the NF-κB pathway, inhibiting Wnt/β-catenin signaling in brain endothelial cells in vitro and in vivo. Cell culture study revealed that NF-κB p65 directly interacted with β-catenin to suppress Wnt/β-catenin signaling. Pharmacological NF-κB pathway inhibition restored brain endothelial Wnt/β-catenin signaling activity and mitigated BBB disruption and neuroinflammation in septic mice. Furthermore, genetic or pharmacological activation of brain endothelial Wnt/β-catenin signaling substantially alleviated LPS-induced BBB leakage and neuroinflammation, while endothelial conditional ablation of the Wnt7a/7b co-receptor Gpr124 exacerbated the BBB leakage caused by LPS. Mechanistically, Wnt/β-catenin signaling activation rectified the reduced expression levels of tight junction protein ZO-1 and transcytosis suppressor Mfsd2a in brain endothelial cells of mice with endotoxemia, inhibiting both paracellular and transcellular permeability of the BBB. Our findings demonstrate that endotoxemia-associated systemic inflammation decreases endothelial Wnt/β-catenin signaling through activating NF-κB pathway, resulting in acute BBB disruption and neuroinflammation. Targeting the endothelial Wnt/β-catenin signaling may offer a promising therapeutic strategy for preserving BBB integrity and treating neurological dysfunction in sepsis., (© 2024. The Author(s).)

Background: Cervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids., Methods: The oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro., Results: CVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication., Conclusions: CVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens., (© 2024. The Author(s).)

Background: Mitochondria play a crucial role in shaping the macrophage inflammatory response during bacterial infections. Spinster homolog 2 (Spns2), responsible for sphingosine-1-phosphate (S1P) secretion, acts as a key regulator of mitochondrial dynamics in macrophages. However, the link between Spns2/S1P signaling and mitochondrial functions remains unclear., Methods: Peritoneal macrophages were isolated from both wild-type and Spns2 knockout rats, followed by non-targeted metabolomics and RNA sequencing analysis to identify the potential mediators through which Spns2/S1P signaling influences the mitochondrial functions in macrophages. Various agonists and antagonists were used to modulate the activation of Spns2/S1P signaling and its downstream pathways, with the underlying mechanisms elucidated through western blotting. Mitochondrial functions were assessed using flow cytometry and oxygen consumption assays, as well as morphological analysis. The impact on inflammatory response was validated through both in vitro and in vivo sepsis models, with the specific role of macrophage-expressed Spns2 in sepsis evaluated using Spns2 flox/flox Lyz2-Cre mice. Additionally, the regulation of mitochondrial functions by Spns2/S1P signaling was confirmed using THP-1 cells, a human monocyte-derived macrophage model., Results: In this study, we unveil prostaglandin E 2 (PGE 2 ) as a pivotal mediator involved in Spns2/S1P-mitochondrial communication. Spns2/S1P signaling suppresses PGE 2 production to support malate-aspartate shuttle activity. Conversely, excessive PGE 2 resulting from Spns2 deficiency impairs mitochondrial respiration, leading to intracellular lactate accumulation and increased reactive oxygen species (ROS) generation through E-type prostanoid receptor 4 activation. The overactive lactate-ROS axis contributes to the early-phase hyperinflammation during infections. Prolonged exposure to elevated PGE 2 due to Spns2 deficiency culminates in subsequent immunosuppression, underscoring the dual roles of PGE 2 in inflammation throughout infections. The regulation of PGE 2 production by Spns2/S1P signaling appears to depend on the coordinated activation of multiple S1P receptors rather than any single one., Conclusions: These findings emphasize PGE 2 as a key effector of Spns2/S1P signaling on mitochondrial dynamics in macrophages, elucidating the mechanisms through which Spns2/S1P signaling balances both early hyperinflammation and subsequent immunosuppression during bacterial infections., (© 2024. The Author(s).)

Objective: To retrospectively explore the clinical significance of radiotherapy to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.) in metastatic cervical cancer. Hereinto, these cervicothoracic lymph nodes were metastasized from IB1-IVA (initial stage at first treatment), and IVB initially had metastatic disease in these areas at diagnosis., Methods: Metastatic cervical cancer only with the distant cervicothoracic metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), without distant parenchymal organs metastasis such as lung, liver, bone, and peritoneum, were enrolled in the analysis. These patients were classified into IB1-IVA and IVB based on their initial stage of first treatment. All patients received IMRT for the distant metastatic lymph nodes. The progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method., Results: Overall, the median PFS was 9 months, and the median OS was 27 months. The subgroup analysis showed that for IB1-IVA, the median PFS was 11 months, and the median OS was 30.5 months. For IVB, the median PFS was 8 months, and the median OS was 16 months., Conclusion: Radiotherapy is beneficial to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), and could effectively bring the longer PFS and OS for metastatic cervical cancer., (© 2024. The Author(s).)

Background: Phosphofructokinase P (PFKP) is a key rate-limiting enzyme in glycolysis, playing a crucial role in various pathophysiological processes. However, its specific function in tumors remains unclear. This study aims to evaluate the expression and specific role of PFKP across multiple tumor types (Pan-cancer) and to explore its potential clinical significance as a therapeutic target in cancer treatment., Methods: We analyzed the expression of PFKP, immune cell infiltration, and patient prognosis across various cancers using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we conducted a series of experiments in lung cancer cells, including Western blot, CCK-8 assay, colony formation assay, transwell migration assay, scratch wound healing assay, LDH release assay, and flow cytometry, to evaluate the impact of PFKP on tumor cells., Results: PFKP was found to be highly expressed in most cancers and identified as a prognostic risk factor. Elevated PFKP expression is associated with poorer clinical outcomes, particularly in lung adenocarcinoma (LUAD). Receiver operating characteristic (ROC) curve analysis indicated that PFKP can effectively differentiate between cancerous and normal tissues. The expression of PFKP in most tumors showed significant correlations with tumor mutational burden (TMB), microsatellite instability (MSI), immune score, and immune cell infiltration. In vitro experiments demonstrated that PFKP overexpression promotes lung cancer cell proliferation and migration while inhibiting apoptosis, whereas PFKP deficiency results in the opposite effects., Conclusion: PFKP acts as an oncogene involved in tumorigenesis and may influence the immune microenvironment within the tumor. Our findings suggest that PFKP could serve as a potential biomarker for predicting prognosis and the efficacy of immunotherapy in tumors., (© 2024. The Author(s).)

Background: Klebsiella pneumoniae (KP), responsible for acute lung injury (ALI) and inflammation of the gastrointestinal tract, is a zoonotic pathogen that poses a threat to livestock farming worldwide. Nevertheless, there is currently no validated vaccine to prevent KP infection. The development of mucosal vaccines against KP using Lactobacillus plantarum (L. plantarum) is an effective strategy., Results: Firstly, the L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c were constructed via homologous recombination to express the aCD11c protein either inducibly or constitutively. Both NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c strains could enhance the adhesion and invasion of L. plantarum on bone marrow-derived dendritic cells (BMDCs), and stimulate the activation of BMDCs compared to the control strain NC8-pSIP409 in vitro. Following oral immunization of mice with NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c, the cellular, humoral, and mucosal immunity were significantly improved, as evidenced by the increased expression of CD4 + IL-4 + T cells in the spleen, IgG in serum, and secretory IgA (sIgA) in the intestinal lavage fluid (ILF). Furthermore, the protective effects of L. plantarum against inflammatory damage caused by KP infection were confirmed by assessing the bacterial loads in various tissues, lung wet/dry ratio (W/D), levels of inflammatory cytokines, and histological evaluation, which influenced T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood and lung., Conclusions: Both the inducible and constitutive L. plantarum strains NC8-pSIP409-aCD11c' and NC8-pLc23-aCD11c have been found to stimulate cellular and humoral immunity levels and alleviate the inflammatory response caused by KP infection. These findings have provided a basis for the development of a novel vaccine against KP., (© 2024. The Author(s).)

Background: The increased resistance rate of Salmonella to third-generation cephalosporins represented by ceftriaxone (CRO) may result in the failure of the empirical use of third-generation cephalosporins for the treatment of Salmonella infection in children. The present study was conducted to evaluate a novel method for the rapid detection of CRO-resistant Salmonella (CRS)., Methods: We introduced the concept of the ratio of optical density (ROD) with and without CRO and combined it with matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) to establish a new protocol for the rapid detection of CRS., Results: The optimal incubation time and CRO concentration determined by the model strain test were 2 h and 8 µg/ml, respectively. We then conducted confirmatory tests on 120 clinical strains. According to the receiver operating characteristic curve analysis, the ROD cutoff value for distinguishing CRS and non-CRS strains was 0.818 [area under the curve: 1.000; 95% confidence interval: 0.970-1.000; sensitivity: 100.00%; specificity: 100%; P < 10 - 3 ]., Conclusions: In conclusion, the protocol for the combined ROD and MALDI-TOF MS represents a rapid, accurate, and economical method for the detection of CRS., (© 2024. The Author(s).)

Accurate survival prediction for Non-Small Cell Lung Cancer (NSCLC) patients remains a significant challenge for the scientific and clinical community despite decades of advanced analytics. Addressing this challenge not only helps inform the critical aspects of clinical study design and biomarker discovery but also ensures that the 'right patient' receives the 'right treatment'. However, survival prediction is a highly complex task, given the large number of 'omics; and clinical features, as well as the high degree of freedom that drive patient survival. Prior knowledge could play a critical role in uncovering the complexity of a disease and understanding the driving factors affecting a patient's survival. We introduce a methodology for incorporating prior knowledge into machine learning-based models for prediction of patient survival through Knowledge Graphs, demonstrating the advantage of such an approach for NSCLC patients. Using data from patients treated with immuno-oncologic therapies in the POPLAR (NCT01903993) and OAK (NCT02008227) clinical trials, we found that the use of knowledge graphs yielded significantly improved hazard ratios, including in the POPLAR cohort, for models based on biomarker tumor mutation burden compared with those based on knowledge graphs. Use of a model-defined mutational 10-gene signature led to significant overall survival differentiation for both trials. We provide parameterized code for incorporating knowledge graphs into survival analyses for use by the wider scientific community., (© 2024. The Author(s).)

Chronic obstructive pulmonary disease (COPD) has been associated with alterations in the brain cortical structure. Nonetheless, the causality between COPD and brain cortical structure has not been determined. In the present study, we used Mendelian randomization (MR) analysis to explore the causal effects of genetic predicated COPD on brain cortical structure, namely cortical surface area (SA) and cortical thickness (TH). Genetic association summary data for COPD were obtained from the FinnGen consortium (N = 358,369; Ncase = 20,066). PRISm summary genetic data were retrieved from a case-control GWAS conducted in the UK Biobank (N = 296,282). Lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC, were extracted from a meta-analysis of the UK Biobank and SpiroMeta consortium (N = 400,102). Brain cortical structure data were obtained from the ENIGMA consortium (N = 51,665). Inverse-variance weighted (IVW) method was used as the primary analysis, and a series of sensitivity tests were exploited to evaluate the heterogeneity and pleiotropy of our results. The results identified potential causal effects of COPD on several brain cortical specifications, including pars orbitalis, cuneus and inferior parietal gyrus. Furthermore, genetic predicated lung function index (FEV1, FVC and FEV1/FVC), as well as PRISm, also has causal effects on brain cortical structure. According to our results, a total of 15 functional specifications were influenced by lung function index and PRISm. These findings contribute to understanding the causal effects of COPD and lung function to brain cortical structure., (© 2024. The Author(s).)

Background: Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain., Methods: Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures., Results: We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08)., Conclusions: This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques., (© 2024. The Author(s).)

Background: Post-ERCP pancreatitis is one of the most common adverse events in ERCP-related procedures. The purpose of this study is to construct an online model to predict the risk of post-ERCP pancreatitis in non-elderly patients with common bile duct stones through screening of relevant clinical parameters., Methods: A total of 919 cases were selected from 7154 cases from a major Chinese tertiary hospital. Multivariable logistic regression model was fitted using the variables selected by the LASSO regression from 28 potential predictor variables. The internal and external validation was assessed by evaluating the receiver operating characteristic curve and the area under curve. Restricted cubic spline modelling was used to explore non-linear associations. The interactive Web application developed for risk prediction was built using the R "shiny" package., Results: The incidence of post-ERCP pancreatitis was 5.22% (48/919) and significantly higher in non-elderly patients with female, high blood pressure, the history of pancreatitis, difficult intubation, endoscopic sphincterotomy, lower alkaline phosphatase and smaller diameter of common bile duct. The predictive performance in the test and external validation set was 0.915 (95% CI, 0.858-0.972) and 0.838 (95% CI, 0.689-0.986), respectively. The multivariate restricted cubic spline results showed that the incidence of pancreatitis was increased at 33-50 years old, neutrophil percentage > 58.90%, hemoglobin > 131 g/L, platelet < 203.04 or > 241.40 × 109/L, total bilirubin > 18.39 umol / L, aspartate amino transferase < 36.56 IU / L, alkaline phosphatase < 124.92 IU / L, Albumin < 42.21 g / L and common bile duct diameter between 7.25 and 10.02 mm. In addition, a web server was developed that supports query for immediate PEP risk., Conclusion: The visualized networked version of the above model is able to most accurately predict the risk of PEP in non-elderly patients with choledocholithiasis and allows clinicians to assess the risk of PEP in real time and provide preventive treatment measures as early as possible., (© 2024. The Author(s).)

Background: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH., Methods: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration., Results: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH., Conclusion: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway., (© 2024. The Author(s).)

Background: Febrile seizures (FS) are the most common seizure disorder in children and a common neurologic complication in children with coronavirus disease 2019 (COVID-19). This study aimed to identify differences in clinical characteristics and disease burden between FS with and without COVID-19., Materials and Methods: We conducted a retrospective analysis of medical data at our hospital from December 2019 to July 2023, focusing on hospitalized patients under the age of 14 diagnosed with FS who underwent COVID-19 polymerase chain reaction (PCR) testing. Descriptive statistics and analysis of variance were employed to compare the COVID-19 and non-COVID-19 groups in terms of clinical characteristics and disease burden., Results: A total of 514 patients were included, with 106 testing positive for COVID-19 and 408 testing negative. Patients with COVID-19 were older (34.87 ± 6.16 vs. 28.61 ± 11.35 months, P < 0.001) and had a higher proportion of males (79.2% vs. 62.3%, P = 0.001). The COVID-19 group had longer seizure durations (4.57 ± 4.38 vs. 3.22 ± 2.91 min, P = 0.006) and more complex FS (25.5% vs. 15.9%, P = 0.022). Laboratory tests showed lower lymphocyte counts in the COVID-19 group (1.87 ± 1.48 vs. 2.75 ± 1.51 × 103/µL, P < 0.001) and higher creatine kinase levels (158.49 ± 82.89 vs. 110.89 ± 56.11 U/L, P < 0.001). No significant differences were found in hospital costs, length of hospitalization, and intensive care unit admissions., Conclusion: Clinicians should be knowledgeable about the distinct clinical characteristics of FS in children with COVID-19. Despite distinct features, the prognosis remains favorable and does not require excessive intervention. Ongoing monitoring and research are needed to fully understand the impact of COVID-19 on FS and optimize management strategies., (© 2024. The Author(s).)

Background: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease characterized by the inability of all pulmonary veins to connect to the left atrium. Our previous bibliometric article summarized the characteristics of only the 100 most cited papers in TAPVC research. The purpose of this study was to use comprehensive bibliometric analysis to examine the development history, current status, and future trends in the field of TAPVC., Methods: All publications on TAPVC published between 2000 and 2023 were collected from the Web of Science Core Collection. The publication and citation data were quantitatively analyzed by publication year, country, institution, author, and journal. Co-authorship and co-occurrence analyses were performed using VOSviewer, and keyword and reference bursts were identified using CiteSpace. Pearson's test was used to examine the correlations between two continuous variables., Results: As of July 20, 2023, we identified 368 publications with 3320 citations. These publications were published in 132 journals and authored by 1835 researchers from 457 institutions in 47 countries. For the number of publications, the top country, top institution, top author, and top journals were the United States (n = 82), Shanghai Jiao Tong University (n = 13), Huiwen Chen (n = 9), and Annals of Thoracic Surgery and Pediatric Cardiology (n = 29 each), respectively. For the number of citations, the top country, top affiliation, top author, and top journal were the United States (n = 1348), University of Toronto (n = 250), Christopher A. Caldarone (n = 315), and Annals of Thoracic Surgery (n = 746), respectively. The number of national publications significantly correlated with GDP (R = 0.887, P < 0.001), research & development (R&D) expenditure (R = 0.375, P = 0.013), population (R = 0.694, P < 0.001), and journals (R = 0.751, P < 0.001). The number of national citations significantly correlated with GDP (R = 0.881, P < 0.001), R&D expenditure (R = 0.446, P = 0.003), population (R = 0.305, P = 0.037), and journals (R = 0.917, P < 0.001). International collaboration in the field of TAPVC was not well developed. The most commonly cited publication discussed era changes in mortality and reoperation rate in TAPVC patients. The most common keywords were "total anomalous pulmonary venous connection" and "congenital heart disease". The keyword "case report" appeared most recently, with an average occurrence year of 2021.8. The co-occurrence analysis grouped 26 keywords into six themes: surgical repair of TAPVC, postoperative pulmonary vein stenosis, surgical repair of TAPVC patients with heterotaxy, application of echocardiography in diagnosing TAPVC, application of echocardiography in the prenatal diagnosis of TAPVC, and application of the sutureless technique in the surgical repair of TAPVC patients with right atrial isomerism or a single ventricle. Citation burst detection identified 32 references with citation bursts, seven of which had ongoing citation bursts until 2023., Conclusions: This study conducted a bibliometric analysis to provide a comprehensive overview of TAPVC research. We hope to offer new ideas for promoting development in the field of TAPVC., (© 2024. The Author(s).)

Obesity, a burgeoning global health issue, is increasingly recognized for its detrimental effects on the central nervous system, particularly concerning the integrity of the blood-brain barrier (BBB). This manuscript delves into the intricate relationship between obesity and BBB dysfunction, elucidating the underlying phenotypes and molecular mechanisms. We commence with an overview of the BBB's critical role in maintaining cerebral homeostasis and the pathological alterations induced by obesity. By employing a comprehensive literature review, we examine the structural and functional modifications of the BBB in the context of obesity, including increased permeability, altered transport mechanisms, and inflammatory responses. The manuscript highlights how obesity-induced systemic inflammation and metabolic dysregulation contribute to BBB disruption, thereby predisposing individuals to various neurological disorders. We further explore the potential pathways, such as oxidative stress and endothelial cell dysfunction, that mediate these changes. Our discussion culminates in the summary of current findings and the identification of knowledge gaps, paving the way for future research directions. This review underscores the significance of understanding BBB dysfunction in obesity, not only for its implications in neurodegenerative diseases but also for developing targeted therapeutic strategies to mitigate these effects., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients., Methods: Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively., Results: Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43-NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro., Conclusions: Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation., (© 2024. The Author(s).)

Background: Climate change has led to severe cold events, adversely impacting global crop production. Eggplant (Solanum melongena L.), a significant economic crop, is highly susceptible to cold damage, affecting both yield and quality. Unraveling the molecular mechanisms governing cold resistance, including the identification of key genes and comprehensive transcriptional regulatory pathways, is crucial for developing new varieties with enhanced tolerance., Results: In this study, we conducted a comparative analysis of leaf physiological indices and transcriptome sequencing results. The orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted peroxidase (POD) activity and soluble protein as crucial physiological indicators for both varieties. RNA-seq data analysis revealed that a total of 7024 and 6209 differentially expressed genes (DEGs) were identified from variety "A" and variety "B", respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of DEGs demonstrated that the significant roles of starch and sucrose metabolism, glutathione metabolism, terpenoid synthesis, and energy metabolism (sucrose and starch metabolism) were the key pathways in eggplant. Weighted gene co-expression network analysis (WGCNA) shown that the enrichment of numerous cold-responsive genes, pathways, and soluble proteins in the MEgrep60 modules. Core hub genes identified in the co-expression network included POD, membrane transporter-related gene MDR1, abscisic acid-related genes, growth factor enrichment gene DELLA, core components of the biological clock PRR7, and five transcription factors. Among these, the core transcription factor MYB demonstrated co-expression with signal transduction, plant hormone, biosynthesis, and metabolism-related genes, suggesting a pivotal role in the cold response network., Conclusion: This study integrates physiological indicators and transcriptomics to unveil the molecular mechanisms responsible for the differences in cold tolerance between the eggplant cold-tolerant variety "A" and the cold-sensitive variety "B". These mechanisms include modulation of reactive oxygen species (ROS), elevation in osmotic carbohydrate and free proline content, and the expression of terpenoid synthesis genes. This comprehensive understanding contributes valuable insights into the molecular underpinnings of cold stress tolerance, ultimately aiding in the improvement of crop cold tolerance., (© 2024. The Author(s).)

Aims: Sodium tanshinone IIA sulfonate (STS) injection has been widely used as adjunctive therapy for pulmonary heart disease (PHD) in China. Nevertheless, the efficacy of STS injection has not been systematically evaluated so far. Hence, the efficacy of STS injection as adjunctive therapy for PHD was explored in this study., Methods: Randomized controlled trials (RCTs) were screened from China Science and Technology Journal Database, China National Knowledge Infrastructure, Wanfang Database, PubMed, Sino-Med, Google Scholar, Medline, Chinese Biomedical Literature Database, Cochrane Library, Embase and Chinese Science Citation Database until 20 January 2024. Literature searching, data collection and quality assessment were independently performed by two investigators. The extracted data was analyzed with RevMan 5.4 and STATA 14.0. Basing on the methodological quality, dosage of STS injection, control group measures and intervention time, sensitivity analysis and subgroup analysis were performed., Results: 19 RCTs with 1739 patients were included in this study. Results showed that as adjunctive therapy, STS injection combined with Western medicine showed better therapeutic efficacy than Western medicine alone for PHD by increasing the clinical effective rate (RR = 1.22; 95% CI, 1.17 to 1.27; p < 0.001), partial pressure of oxygen (MD = 10.16; 95% CI, 5.07 to 15.24; p < 0.001), left ventricular ejection fraction (MD = 8.66; 95% CI, 6.14 to 11.18; p < 0.001) and stroke volume (MD = 13.10; 95% CI, 11.83 to 14.38; p < 0.001), meanwhile decreasing the low shear blood viscosity (MD = -1.16; 95% CI, -1.57 to -0.74; p < 0.001), high shear blood viscosity (MD = -0.64; 95% CI, -0.86 to -0.42; p < 0.001), plasma viscosity (MD = -0.23; 95% CI, -0.30 to -0.17; p < 0.001), hematokrit (MD = -8.52; 95% CI, -11.06 to -5.98; p < 0.001), fibrinogen (MD = -0.62; 95% CI, -0.87 to -0.37; p < 0.001) and partial pressure of carbon dioxide (MD = -8.56; 95% CI, -12.09 to -5.02; p < 0.001)., Conclusion: STS injection as adjunctive therapy seemed to be more effective than Western medicine alone for PHD. However, due to low quality of the included RCTs, more well-designed RCTs were necessary to verify the efficacy of STS injection., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has presented significant challenges to the already over-stretched healthcare system in the United Kingdom (UK). These challenges are particularly pronounced for people living with the novel condition of Long COVID (LC) as they often face persistent and fluctuating symptoms, encountering prolonged uncertainty when seeking medical support. Despite a growing understanding of the healthcare challenges associated with LC, existing qualitative studies have predominantly focused on individual experiences rather than examining the structural aspects of healthcare., Methods: A longitudinal qualitative study with 80 participants and 12 healthcare practitioners was conducted in the UK to explore the healthcare experiences of those with LC. In total, 178 interviews (with attrition) were collected across two rounds, from November 2021 to March 2022, and from June to October 2022., Results: Embracing a person-centred framework that recognises and nurtures interconnected individual, relational, and existential needs, we investigated healthcare experiences related to LC across primary, secondary, and specialist integrated care. Using this perspective, we identified three overarching themes. Theme 1 addresses the persistent hurdle of accessing primary care as the initial point of contact for LC healthcare; Theme 2 underscores the complexity of navigating secondary care; and Theme 3 encapsulates the distinctive challenges of developing LC integrated care. These themes are interlinked, as people with LC often had to navigate or struggle between the various systems, with practitioners seeking to collaborate across the breadth of their professional responsibilities., Conclusion: From a person-centred approach, we were able to identify the needs of those affected by lasting LC symptoms and comprehend how health services intricately influence these needs. The focus on healthcare systems also captures the nuanced impact that continuing healthcare struggles can have on people's identity. As such, our findings provide evidence to inform a more effective and sustainable delivery of person-centred care for people with LC across various healthcare settings and over time., (© 2024. The Author(s).)

Background: Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis., Methods: Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB., Results: The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway., Conclusions: The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage., (© 2024. The Author(s).)

Objective: To evaluate the dynamics of basic activity of daily living (BADL) in older patients with acute lower respiratory tract infections (LRTIs) during acute phase and to investigate risk factors associated with decreased physical function at discharge., Methods: We conducted a prospective cohort study of patients aged 65 years and older who were hospitalized for acute LRTIs between April 15, 2020 and January 15, 2023. All patients received geriatric assessment at admission, including emotion, cognition, frailty, physical function status and so on. The BADL was also evaluated by the Barthel Index (BI) at two weeks before admission by recall (baseline status), at admission and at discharge. Based on the BI grades at baseline and at discharge, patients were classified into two groups: ADL decline and no ADL decline. Multivariable adjusted logistic regression models were used to evaluate the risk factors of decreased physical function., Results: A total of 364 older survivors with LRTIs were included in the analysis. The median age was 74 years (IQR 61.0-82.0), 231 (62.6%) were male, the median length of stay was 10 days. In the geriatric assessment, 139 patients (38.2%) were classified as frailty, 137 patients (37.6%) experienced insomnia, 60 patients (16.5%) exhibited cognitive impairments, and 37 patients (10.2%) were defined as malnutrition. Additionally, 30 patients (8.2%) dealt with emotional disorders. On average, patients were taking 3 medications, and Charlson Comorbidity Index score was 4. 72 patients (19.8%) had function decline at discharge. In the multivariable analysis, frailty status had an odds ratio of 4.25 (95% CI 1.31-19.26) for decreased physical function and cognitive impairment had an odds ratio of 2.58 (95% CI 1.27-5.19)., Conclusions: About 20% older patients with LRTIs experienced functional decline at discharge. Compared to age, severity of diseases and length of stay, frailty and cognitive impairment performed better at predicting the function decline. The apply of geriatric assessment may contribute to enhance the quality of management and treatment for patients with the older with LRTIs., (© 2024. The Author(s).)

Background: In paddy fields, the noxious weed barnyard grass secretes 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) to interfere with rice growth. Rice is unable to synthesize DIMBOA. Rice cultivars with high or low levels of allelopathy may respond differently to DIMBOA., Results: In this study, we found that low concentrations of DIMBOA (≤ 0.06 mM) promoted seedling growth in allelopathic rice PI312777, while DIMBOA (≤ 0.08 mM) had no significant influence on the nonallelopathic rice Lemont. DIMBOA treatment caused changes in the expression of a large number of glutathione S-transferase (GST) proteins, which resulting in enrichment of the glutathione metabolic pathway. This pathway facilitates plant detoxification of heterologous substances. The basal levels of GST activity in Lemont were significantly higher than those in PI312777, while GST activity in PI312777 was slightly induced by increasing DIMBOA concentrations. Overexpression of GST genes (Os09g0367700 and Os01g0949800) in these two cultivars enhanced rice resistance to DIMBOA., Conclusions: Taken together, our results indicated that different rice accessions with different levels of allelopathy have variable tolerance to DIMBOA. Lemont had higher GST activity, which helped it tolerate DIMBOA, while PI312777 had lower GST activity that was more inducible. The enhancement of GST expression facilitates rice tolerance to DIMBOA toxins from barnyard grass root exudates., (© 2024. The Author(s).)

Tumor cells primarily employ the PD-1/PD-L1 pathway to thwart the anti-tumor capabilities of T lymphocytes, inducing immunosuppression. This occurs through the direct interaction of PD-L1 with PD-1 on T lymphocyte surfaces. Recent research focusing on the tumor microenvironment has illuminated the pivotal role of immune cells, particularly tumor-associated macrophages (TAMs), in facilitating PD-L1-mediated immunosuppression. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. Exosomes, characterized by their ability to convey information and be engulfed by cells, significantly contribute to promoting TAM involvement in establishing PD-L1-mediated immunosuppression within the tumor microenvironment. In addition to receiving signals from tumor-derived exosomes that promote PD-L1 expression, TAMs also exert control over PD-L1 expression in tumor cells through the release of exosomes. This paper aims to summarize the mechanisms by which exosomes participate in this process, identify crucial factors that influence these mechanisms, and explore innovative strategies for inhibiting or reversing the tumor-promoting effects of TAMs by targeting exosomes., (© 2024. The Author(s).)

Background: Cholangiocarcinoma (CCA) is a highly malignant and easily metastatic bile duct tumor with poor prognosis. We aimed at studying the associated risk factors affecting distal metastasis of CCA and using nomogram to guide clinicians in predicting distal metastasis of CCA., Methods: Based on inclusion and exclusion criteria, 345 patients with CCA were selected from the Fifth Medical Center of Chinese PLA General Hospital and were divided into distal metastases (N = 21) and non-distal metastases (N = 324). LASSO regression models were used to screen for relevant parameters and to compare basic clinical information between the two groups of patients. Risk factors for distal metastasis were identified based on the results of univariate and multivariate logistic regression analyses. The nomogram was established based on the results of multivariate logistic regression, and we drawn the corresponding correlation heat map. The predictive accuracy of the nomogram was evaluated by receiver operating characteristic (ROC) curves and calibration plots. The utility of the model in clinical applications was illustrated by applying decision curve analysis (DCA), and overall survival(OS) analysis was performed using the method of Kaplan-meier., Results: This study identified 4 independent risk factors for distal metastasis of CCA, including CA199, cholesterol, hypertension and margin invasion, and developed the nomogram based on this. The result of validation showed that the model had significant accuracy for diagnosis with the area under ROC (AUC) of 0.882 (95% CI: 0.843-0.914). Calibration plots and DCA showed that the model had high clinical utility., Conclusions: This study established and validated a model of nomogram for predicting distal metastasis in patients with CCA. Based on this, it could guide clinicians to make better decisions and provide more accurate prognosis and treatment for patients with CCA., (© 2023. The Author(s).)

Background: Several studies have demonstrated that secondary cytoreductive surgery (SCS) for patients with recurrent uterine malignancies may improve the survival. However, the selection criteria for SCS remain to be defined. This study aimed to assess the outcome of SCS and to explore factors that may influence the prognosis., Methods: Data of patients with recurrent uterine malignancies who received SCS in our hospital between January 2005 and January 2015 were retrospectively analyzed. Patients were assigned into endometrial carcinoma (EC) group and uterine sarcoma (US) group., Results: 84 cases in total were involved in the study, including 47 cases with recurrent EC and 37 cases with recurrent US. The 5-year survival of cases with recurrent EC and recurrent US was 59.6% and 33.3%, respectively. Recurrent EC cases with a lower tumor grade (G1/G1-G2/G2), size of the largest tumor ≤ 6 cm, single recurrent tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer disease-free interval (DFI) before SCS (≥ 12 months), no peritoneal dissemination, and a history of complete cytoreduction were associated with a longer survival. The number of recurrent tumors was found as an independent prognostic factor of SCS., Conclusion: Recurrent EC cases with a lower tumor grade, smaller tumor size, single tumor, a history of adjuvant therapy, as well as recurrent US cases with younger age, a longer DFI before SCS, no peritoneal dissemination, and a history of complete cytoreduction were more likely to benefit from SCS., (© 2023. The Author(s).)

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients., (© 2023. The Author(s).)

Noise exposure is an important cause of acquired hearing loss. Studies have found that noise exposure causes dysregulated redox homeostasis in cochlear tissue, which has been recognized as a signature feature of hearing loss. Oxidative stress plays a pivotal role in many diseases via very complex and diverse mechanisms and targets. Reactive oxygen species are products of oxidative stress that exert toxic effects on a variety of physiological activities and are considered significant in noise-induced hearing loss (NIHL). Endogenous cellular antioxidants can directly or indirectly counteract oxidative stress and regulate intracellular redox homeostasis, and exogenous antioxidants can complement and enhance this effect. Therefore, antioxidant therapy is considered a promising direction for NIHL treatment. However, drug experiments have been limited to animal models of NIHL, and these experiments and related observations are difficult to translate in humans; therefore, the mechanisms and true effects of these drugs need to be further analyzed. This review outlines the effects of oxidative stress in NIHL and discusses the main mechanisms and strategies of antioxidant treatment for NIHL., (© 2023. The Author(s).)

Background: Berberine (BBR) is a commonly used anti-intestinal inflammation drug, and its anti-cancer activity has been found recently. BBR can intervene and control malignant colorectal cancer (CRC) through intestinal microbes, but the direct molecular target and related mechanism are unclear. This study aimed to identify the target of BBR and dissect related mechanisms against the occurrence and development of CRC from the perspective of intestinal microorganisms., Results: Here, we found that BBR inhibits the growth of several CRC-driving bacteria, especially Peptostreptococcus anaerobius. By using a biotin-conjugated BBR derivative, we identified the protein FtfL (formate tetrahydrofolate ligase), a key enzyme in C1 metabolism, is the molecular target of BBR in P. anaerobius. BBR exhibits strong binding affinity and potent inhibition on FtfL. Based on this, we determined the crystal structure of PaFtfL (P. anaerobius FtfL)-BBR complex and found that BBR can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active center. In addition, the enzymatic activities of FtfL homologous proteins in human tumor cells can also be inhibited by BBR., Conclusions: In summary, our study has identified FtfL as a direct target of BBR and uncovered molecular mechanisms involved in the anti-CRC of BBR. BBR interferes with intestinal pathogenic bacteria by targeting FtfLs, suggesting a new means for controlling the occurrence and development of CRC., (© 2023. The Author(s).)

Background: Current research on autophagy is mainly focused on intervertebral disc tissues and cells, while there is few on human peripheral blood sample. therefore, this study constructed a diagnostic model to identify autophagy-related markers of intervertebral disc degeneration (IVDD)., Methods: GSE150408 and GSE124272 datasets were acquired from the Gene Expression Omnibus database, and differential expression analysis was performed. The IVDD-autophagy genes were obtained using Weighted Gene Coexpression Network Analysis, and a diagnostic model was constructed and validated, followed by Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Meanwhile, miRNA-gene and transcription factor-gene interaction networks were constructed. In addition, drug-gene interactions and target genes of methylprednisolone and glucosamine were analyzed., Results: A total of 1,776 differentially expressed genes were identified between IVDD and control samples, and the composition of the four immune cell types was significantly different between the IVDD and control samples. The Meturquoise and Mebrown modules were significantly related to immune cells, with significant differences between the control and IVDD samples. A diagnostic model was constructed using five key IVDD-autophagy genes. The area under the curve values of the model in the training and validation datasets were 0.907 and 0.984, respectively. The enrichment scores of the two pathways were significantly different between the IVDD and healthy groups. Eight pathways in the IVDD and healthy groups had significant differences. A total of 16 miRNAs and 3 transcription factors were predicted to be of great value. In total, 84 significantly related drugs were screened for five key IVDD-autophagy genes in the diagnostic model, and three common autophagy-related target genes of methylprednisolone and glucosamine were predicted., Conclusion: This study constructs a reliable autophagy-related diagnostic model that is strongly related to the immune microenvironment of IVD. Autophagy-related genes, including PHF23, RAB24, STAT3, TOMM5, and DNAJB9, may participate in IVDD pathogenesis. In addition, methylprednisolone and glucosamine may exert therapeutic effects on IVDD by targeting CTSD, VEGFA, and BAX genes through apoptosis, as well as the sphingolipid and AGE-RAGE signaling pathways in diabetic complications., (© 2023. The Author(s).)

Background: Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated., Objective: This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality., Methods: This study included participants from the National Health and Nutrition Examination Survey 2011-2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied., Results: This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p < 0.05). Compared with the participant in tertile 1 of serum Cu (< 16.31 mol/L), those in tertile 3 (≥ 19.84 mol/L) were significantly associated with CVD mortality (HR: 7.06, 95%CI: 1.85,26.96), and all-cause mortality (HR: 2.84, 95% CI: 1.66,4.87). The dose-response curve indicated a linear relationship between serum Cu and CVD mortality (p -nonlinear = 0.48) and all-cause (p -nonlinear = 0.62). A meta-analysis included additional three prospective cohorts with 13,189 patients confirmed the association between higher serum Cu and CVD (HR: 2.08, 95% CI: 1.63,2.65) and all-cause mortality (HR: 1.89, 95%CI: 1.58,2.25)., Conclusion: The present study suggests excessive serum Cu concentrations are associated with the risk of CVD and all-cause mortality in American adults. Our findings and the causal relationships require further investigation., (© 2023. The Author(s).)

Background: Endovascular recanalization in patients with symptomatic nonacute intracranial large artery occlusion (ILAO) has been reported to be feasible, but technically challenging. This study aimed to determine the predictors of successful endovascular recanalization in patients with symptomatic nonacute ILAO., Methods: The outcomes of endovascular recanalization attempts performed in 70 consecutive patients showing symptomatic nonacute ILAO with hemodynamic cerebral ischemia between January 2016 to December 2022 were reviewed. Potential variables, including clinical and radiological characteristics related to technical success, were collected. Univariate analysis and multivariate logistic regression were performed to identify predictors of successful recanalization for nonacute ILAO., Results: Technically successful recanalization was achieved in 57 patients (81.4%). The periprocedural complication rate was 21.4% (15 of 70), and the overall 30-day morbidity and mortality rates were 7.1% (5 of 70) and 2.9% (2 of 70), respectively. Univariate analysis showed that successful recanalization was associated with occlusion duration, stump morphology, occlusion length, slow distal antegrade flow sign, and the presence of bridging collateral vessels. Multivariate analysis showed that occlusion duration ≤ 3 months (odds ratio [OR]: 22.529; 95% confidence interval [CI]: 1.636-310.141), tapered stump (OR: 7.498; 95% CI: 1.533-36.671), and occlusion length < 10 mm (OR: 7.049; 95% CI: 1.402-35.441) were independent predictive factors for technical success of recanalization., Conclusions: Occlusion duration ≤ 3 months, tapered stump, and occlusion length < 10 mm were independent positive predictors of technical success of endovascular recanalization for symptomatic nonacute ILAO. These findings may help predict the likelihood of successful recanalization in patients with symptomatic nonacute ILAO and also provide a reference for the selection of appropriate patients. Further prospective and multicenter studies are required to validate our findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The prognostic significance of serum uric acid (SUA) in individuals who have experienced myocardial infarction (MI) remains a subject of academic debate. Thus, the aim of this study was to examine the occurrence of immediate and long-term adverse outcomes in individuals with elevated levels of uric acid (UA) following a diagnosis of MI., Method: This study conducted a literature search from PubMed, Embase, Web of Science, Medline, Cochrane Library, Emcrae, and Scopus to perform a systematic review and meta-analysis of the prognostic impact of MI with a hyper SUA to assess short-term (30-day or in-hospital) and long-term mortality, the incidence of major adverse cardiovascular events (MACE), and its adverse event rate in relation to SUA. The literature search was conducted up until April 2023. A random effects model and risk ratio (RR) were used as epidemiological indicators. For indicators with low disease rates, treatment intensity was reduced and RR was considered equivalent to odds ratio (OR). Hazard Ratio (HR), RR, and OR extracted from the data were simultaneously subjected to multivariable adjustment for confounding factors. In addition, P values for all original hypotheses were extracted and a meta-analysis was conducted. High SUA was defined as SUA levels equal to or greater than 420 μmol/L (7.0 mg/dL) for males and equal to or greater than 357 μmol/L (6.0 mg/dL) for females. The quality of the literature was evaluated using the Newcastle-Ottawa Scale (NOS)., Results: This comprehensive study included a total of 41 investigations, involving a large sample size of 225,600 individuals who had experienced MI. The findings from the meta-analysis reveal that patients diagnosed with hyperuricemia have significantly increased rates of short-term mortality (RR = 2.14, 95% CI = 1.86, 2.48) and short-term incidence of MACE (RR = 1.94, 95% CI = 1.65-2.11). Furthermore, long-term adverse outcomes, including all-cause mortality (RR = 1.46, 95% CI = 1.40-1.51) and incidence of MACE (RR = 1.43, 95% CI = 1.35-1.52), were also found to be higher in this specific patient population., Conclusion: Patients diagnosed with MI and elevated SUA levels exhibit a heightened incidence of MACE during their hospital stay. Furthermore, these individuals also experience elevated rates of in-hospital mortality and mortality within one year of hospitalization. However, it is important to note that further randomized controlled trials are necessary to validate and authenticate these findings., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Assisted reproductive technologies (ART) have increased the incidence of multiple births, which can have a negative impact on maternal and offspring health. The study aimed to investigate the association between genetically predicted multiple birth and the risk of 42 common diseases of the nervous, psychiatric, cardiovascular, respiratory, digestive, and endocrine systems., Methods: The study utilized two-sample Mendelian randomization (MR) analysis to explore the potential causal relationship between genetically predicted multiple birth and the genetically predicted risk of diseases. The study used the FinnGen and UK Biobank datasets for analysis., Results: The study found no significant causal relationship between multiple birth and psychiatric disorders. However, the lower limits of the 95% confidence intervals for bipolar affective disorder and anxiety disorders were not robust, indicating a need for further investigation. The study found that multiple birth may be a strong risk factor for infantile cerebral palsy, and caution is necessary in both natural and ART multiple births. The study revealed a potential causal relationship between multiple birth and coronary heart disease, ischemic heart disease, and deep vein thrombosis, which may be related to abnormal intrauterine environments in multiple pregnancies. Surprisingly, multiple birth appears to have a protective effect against some respiratory diseases, such as chronic obstructive pulmonary disease and asthma., Conclusions: The study highlights the need for caution regarding the risk of infantile cerebral palsy, cardiovascular diseases, and psychiatric disorders in multiple birth. Our study can lead to the development of preventive strategies and improved clinical management for affected infants., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Tuberculosis is a high-burden disease and a major health concern in China, especially among children and adolescents. The purpose of this study was to assess risk factors for diagnostic delay in students with pulmonary tuberculosis in Quzhou City in eastern China., Patients and Methods: Cases of PTB in students and relevant information in Quzhou from 2011 to 2021 were collected using the TB Management Information System. The outcome of interest was diagnostic delay (i.e. ≥ 28 days between symptom onset and treatment initiation). Risk factors for diagnostic delay were identified using multivariable logistic regression., Results: A total of 629 students in Quzhou were diagnosed with PTB during the study period, of whom 55.5% were male. The median diagnostic delay was 18 days (Inter Quartile Range, [IQR]: 8-38) and 38.0% of the students had a diagnostic delay. Living in a rural area (adjusted odds ratio, [AOR]: 1.56, 95% confidence interval [CI:] 1.11-2.19), developing PTB symptoms in the first quarter of the year (AOR: 2.18, 95% CI: 1.40-3.40), and no sputum smear result (AOR: 8.73, 95% CI: 1.68-45.30) were significantly associated with a diagnostic delay. Discovery through health examinations (AOR: 0.33, 95% CI: 0.17-0.63) was associated with reduced risk of diagnostic delay., Conclusion: Schools in rural areas should pay special attention to increasing student awareness of the symptoms of tuberculosis and provide health education on tuberculosis prevention and control to students and staff., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The perineural invasion (PNI)-mediated inflammation of the tumor microenvironment (TME) varies among gastric cancer (GC) patients and exhibits a close relationship with prognosis and immunotherapy. Assessing the neuroinflammation of TME is important in predicting the response to immunotherapy in GC patients., Methods: Fifteen independent cohorts were enrolled in this study. An inflammatory score was developed and validated in GC. Based on PNI-related prognostic inflammatory signatures, patients were divided into Clusters A and B using unsupervised clustering. The characteristics of clusters and the potential regulatory mechanism of key genes were verified by RT-PCR, western-blot, immunohistochemistry and immunofluorescence in cell and tumor tissue samples.The neuroinflammation infiltration (NII) scoring system was developed based on principal component analysis (PCA) and visualized in a nomogram together with other clinical characteristics., Results: Inflammatory scores were higher in GC patients with PNI compared with those without PNI (P < 0.001). NII.clusterB patients with PNI had abundant immune cell infiltration in the TME but worse prognosis compared with patients in the NII.clusterA patients with PNI and non-PNI subgroups. Higher immune checkpoint expression was noted in NII.clusterB-PNI. VCAM1 is a specific signature of NII.clusterB-PNI, which regulates PD-L1 expression by affecting the phosphorylation of STAT3 in GC cells. Patients with PNI and high NII scores may benefit from immunotherapy. Patients with low nomogram scores had a better prognosis than those with high nomogram scores., Conclusions: Inflammation mediated by PNI is one of the results of tumor-nerve crosstalk, but its impact on the tumor immune microenvironment is complex. Assessing the inflammation features of PNI is a potential method in predicting the response of immunotherapy effectively., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Background: Rectal colonisation with carbapenem-resistant Gram-negative bacilli (CR-GNB) may cause CR-GNB infection in children with haematological malignancies (HMs) haematological. To date, information on its epidemiology is limited. This study aimed to assess the the risk factors for rectal colonisation with CR-GNB in children with HMs., Methods: A case-control study in a tertiary children's hospital in Hangzhou City, was conducted between July 2019, and September 2021. Based on the hospitalisation date, children in the CR-GNB colonisation group and control groups were matched at a ratio of 1:2. Conditional logistic regression models were used to compute the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the risk factors for CR-GNB rectal colonisation in children with HMs., Results: A total of 85 non-duplicated CR-GNB isolates were collected from rectal swab samples of 69 children with HMs. The 30-day mortality rates were 5.8% in the CR-GNB colonisation group and 0% in the control group (P = 0.020).colonisation In the conditional logistic regression model, the aORs were 6.84 (95% CI 1.86-25.20) for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), 4.16 (95% CI 1.17-14.84) for prior concomitant infections within the last 1 month, 2.33 (95% CI 1.16-4.69) for prior carbapenems usage within the last 1 month and 7.46 (95% CI 1.81-30.67) for prior hematopoietic stem-cell transplantation (HSCT)., Conclusion: AML/ALL, prior concomitant infections within the last 1 month, prior carbapenems usage within the last 1 month, and prior HSCT are associated with an increased risk of rectal colonisation with CR-GNB in children with HMs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Previous studies have shown that Family with sequence similarity 134 member B (FAM134B) was involved in the occurrence and development of malignancy, however, the function and molecular mechanism of FAM134B in Hepatocellular Carcinoma (HCC) radiotherapy resistance remain unclear. Therefore, it may clinical effective to clarify the molecular mechanism and identify novel biomarker to overcome radiotherapy resistance in HCC., Methods: The protein and mRNA expression of FAM134B were determined using Real-time PCR and Western blot, respectively. IHC assay was performed to investigate the association between FAM134B expression and the clinicopathological characteristics of 132 HCC patients. Functional assays, such as in situ model, colon formation, FACS, and Tunel assay were used to determine the oncogenic role of FAM134B in human HCC progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM134B promotes radiation-sensitive in HCC cells., Results: We noted that FAM134B was downregulated in HCC, which was correlated with the radiation resistance in patients with HCC. Overexpression of FAM134B contribute to radiation sensitive in HCC; however, inhibition of FAM134B confers HCC cell lines to radiation resistance both in vitro and in vivo. Moreover, we found that FAM134B interacts with FMS related receptor tyrosine kinase 3 (FLT3) and downregulation of FAM134B activated JAK/Stat3 signaling pathway. Importantly, pharmacological inhibition of JAK/Stat3 signaling pathway significantly counteracted downregulation of FAM134B-induced radiation resistance and enhanced radiation therapeutic efficacy in HCC., Conclusions: Our findings suggest that FAM134B may be a potential therapeutic biomarker for the treatment of HCC patients with radiotherapy tolerance., (© 2023. The Author(s).)

Background: Non-invasive prenatal testing (NIPT) using cell-free DNA has been widely used for prenatal screening to detect the common fetal aneuploidies (such as trisomy 21, 18, and 13). NIPT has been shown to be highly sensitive and specific in previous studies, but false positives (FPs) and false negatives (FNs) occur. Although the prevalence of FN NIPT results for Down syndrome is rare, the impact on families and society is significant., Case Presentation: This article described two cases of foetuses that tested "negative" for trisomy 21 by NIPT technology using the semiconductor sequencing platform. However, the fetal karyotypes of amniotic fluid were 46,XY, + 21 der(21;21)(q10;q10) and 47,XY, + 21 karyotypes, respectively. Placental biopsies confirmed that, in the first case, the chromosome 21 placenta chimerism ratio ranged from 13 to 88% with the 46,XX, + 21,der(21;21)(q10;q10)[86]/46,XX[14] karyotype of placental chorionic cells (middle of fetal-side placental tissue). However, in the second case, of all the placental biopsies, percentage of total chimerism was less than 30%; and placental biopsies taken at the middle of maternal side and middle of fetal side, also had variable trisomy 2 mosaicism levels of 10% and 8%, respectively. Ultimately, the pregnancies were interrupted at 30 gestational age (GA) and 27GA, respectively., Conclusions: In this study, we present two cases of FN NIPT results that might have been caused by biological mechanisms, as opposed to poor quality, technical errors, or negligence. Clinical geneticists and their patients must understand that NIPT is a screening procedure., (© 2023. The Author(s).)

Background: Sheep genomes undergo numerous genes losses, gains and mutation that generates genome variability among breeds of the same species after long time natural and artificial selection. However, the microevolution of native sheep in northwest China remains elusive. Our aim was to compare the genomes and relevant reproductive traits of four sheep breeds from different climatic environments, to unveil the selection challenges that this species cope with, and the microevolutionary differences in sheep genomes. Here, we resequenced the genomes of 4 representative sheep breeds in northwest China, including Kazakh sheep and Duolang sheep of native breeds, and Hu sheep and Suffolk sheep of exotic breeds with different reproductive characteristics., Results: We found that these four breeds had a similar expansion experience from ~ 10,000 to 1,000,000 years ago. In the past 10,000 years, the selection intensity of the four breeds was inconsistent, resulting in differences in reproductive traits. We explored the sheep variome and selection signatures by F ST and θπ. The genomic regions containing genes associated with different reproductive traits that may be potential targets for breeding and selection were detected. Furthermore, non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds with different reproductive characteristics were found. We identified PAK1, CYP19A1 and PER1 as a likely causal gene for seasonal reproduction in native sheep through qPCR, Western blot and ELISA analyses. Also, the haplotype frequencies of 3 tested gene regions related to reproduction were significantly different among four sheep breeds., Conclusions: Our results provide insights into the microevolution of native sheep and valuable genomic information for identifying genes associated with important reproductive traits in sheep., (© 2023. The Author(s).)

Background: Most studies support parafunctions play an important role in temporomandibular disorders (TMD), whereas the association between tooth wear and TMD remains controversial. Betel nut chewing as a parafunction is popular in South and Southeast Asia. We therefore investigated the association of severely worn dentition resulting from betel nut chewing with TMD., Methods: A cross-sectional analysis of 408 control participants (male: 380, female: 28, 43.62 ± 9.54 years) and 408 participants with betel nut chewing related severely worn dentition (male: 380, female: 28, 43.73 ± 8.93 years) who received dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Health Management Center, Xiangya Hospital was performed. Betel nut chewing related severely worn dentition meant all the natural teeth had moderate to severe tooth wear [Tooth Wear Index (TWI) ≥ 2)] including ≥ 2 severe wear teeth (TWI ≥ 3) due to betel nut chewing. Multivariable logistic regression analysis was used., Results: After adjusting for age, gender, betel nut chewing related severely worn dentition, oral submucosal fibrosis, number of missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, variables of age, gender and betel nut chewing related severely worn dentition were significant for overall TMD. Multivariable analysis showed betel nut chewing related severely worn dentition was significantly associated with intra-articular TMD [odds ratio and 95% confidence intervals: 1.689 (1.271-2.244), P = 0.001] in a betel nut chewing dose-dependent manner., Conclusion: Betel nut chewing related severely worn dentition was associated with intra-articular TMD., (© 2023. The Author(s).)

Background: The clinical features of mitochondrial cardiomyopathy (MCM) are diverse. It can present as hypertrophic cardiomyopathy or dilated cardiomyopathy. The diagnosis of MCM is challenging and usually based on biopsy., Case Presentation: The 30-year-old man was admitted to hospital due to dyspnea for 1 month and edema of both lower extremities for 1 week. Echocardiography suggested a whole heart enlargement, a whole heart diminished function. Renal impairment and diabetes were observed. Coronary angiography showed single-vessel disease (90% stenosis in the ostium of a small marginal branch). Left ventricular endomyocardial biopsy was performed., Conclusion: Myocardial histopathology demonstrated a large number of abnormal mitochondrial accumulation, so the diagnosis was considered as mitochondrial cardiomyopathy., (© 2023. The Author(s).)

Background: Growing older is often associated with resilience, contentedness and inner growth. Older people however are also at risk of confronting unique emotional challenges as a result of varied ageing-related experiences. By employing a biographical lens, we aim to introduce storytelling as a methodological tool to more holistically explore older people's emotional challenges and to improve their wellbeing., Methods: Building upon theoretical understandings about the narrative construction of identity across the life span, we draw upon a qualitative study about older people's loneliness as an example to showcase the methodological value and feasibility of biographical storytelling. We aim to better understand the nuanced and sometimes painful emotional experiences that can be encountered alongside ageing., Results: Findings from the qualitative study we showcase, highlight that unique emotional pains and the (in)ability to deal with such in old age could be deeply rooted in older people's earlier lives. These findings contextualise people's emotional challenges and needs within their identity, as a narrative thread that links their past, present and expected future. As such, our example study shows that emotional challenges in old age are not only ageing-related, but can be more fundamentally connected to disruptions to the ongoing flow of narrative identity construction., Conclusion: The highly retrospective and reflexive nature of these findings illustrates the methodological merit of biographical storytelling. We argue that the impact of biographical storytelling can go further than both conventional semi-structured narrative interviews and existing interventional tools. Instead, it is a particularly useful research methodology to explore human experiences and needs in the unique context of ageing. This methodological development thus provides an insightful analytical lens to explore how older people's earlier life experiences may be carried forward and confronted to shape their emotional stability in the present and future stages of their ageing lives. Beyond the methodological significance, we further demonstrate the benefits of empowering older people to reconstruct their ageing lives in the context of their biography., (© 2023. The Author(s).)