Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

Relationship between Dietary Inflammatory Index and Blood Glucose Changes in Patients with Pre-diabetes Mellitus.

Objective: The objective of this study was to assess the association between the dietary inflammatory index (DII) and blood glucose changes in patients diagnosed with pre-diabetes mellitus (Pre-DM). Methods: The study participants were 111 patients diagnosed with Pre-DM at Taizhou People's Hospital of Jiangsu Province Hospital between January 2019 and December 2021. Patients' initial BG data were collected and recorded. A dietary assessment was performed on all Pre-DM patients, and the DII of each participant was calculated to explore the relationship between DII and BG changes. DII was calculated based on the relation between food and interleukin serum IL-1ß, IL-4, IL-6, IL-10 and CRP. Results: The fasting (FBG), 1-hour postprandial (1hPBG) and 2-hour postprandial blood glucose (2hPBG) levels were (5.43±0.88) mmol/L, (10.67±3.05) mmol/L, and (8.65±2.89) mmol/L, respectively, with statistical significance among them (n=111, F=222.987, P < .001). Multivariate linear regression models were established with FBG, 1hPBG, 2hPBG, and BG changes (2hPBG-FBG and 1hPBG-FBG) as dependent variables. In Model 5, the coefficient (B value) of DII and its 95% (CI) were 0.324 (0.018~0.658) (P = .031), indicating a positive correlation between DII and BG concentration that the change of BG concentration increased by 0.456 mmol/L for every 1 unit increase in DII. Conclusions: DII is a risk factor for Pre-DM patients, so attention should be paid to the content of inflammatory components in the diet, and more intake of anti-inflammatory components is helpful to prevent the occurrence of diabetes further.

Spatiotemporal development of the neuronal accumulation of amyloid precursor protein and the amyloid plaque formation in the brain of 3xTg-AD mice.

The amyloid plaque is a hallmark of Alzheimer's disease. The accumulation of the amyloid precursor protein (APP) in the neuronal structure is assumed to lead to amyloid plaque formation through the excessive production of ß-amyloid protein. To study the relationship between the neuronal accumulation of APP and amyloid plaque formation, we histologically analyzed their development in the different brain regions in 3xTg-AD mice, which express Swedish mutated APP (APPSWE) in the neurons. Observation throughout the brain revealed APPSWE-positive somata in the broad regions. Quantitative model analysis showed that the somatic accumulation of APPSWE developed firstly in the hippocampus from a very early age (<1 month) and proceeded slower in the isocortex. In line with this, the hippocampus was the first region to form amyloid plaques at the age of 9-12 months, while amyloid plaques were rarely observed in the isocortex. Females had more APPSWE-positive somata and plaques than males. Furthermore, amyloid plaques were observed in the lateral septum and pontine grey, which did not contain APPSWE-positive somata but only the APPSWE-positive fibers. These results suggested that neuronal accumulation of APPSWE, both in somatodendritic and axonal domains, is closely related to the formation of amyloid plaques.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Composite dietary antioxidant index is associated with reduced prevalence of metabolic syndrome but not mortality in metabolic syndrome: Results from NHANES 2001-2018.

The relationship between the composite dietary antioxidant index (CDAI), a comprehensive measure of individual dietary antioxidants, and the prevalence and mortality of metabolic syndrome (MetS) remains unknown. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). We explored these relationships using two independent cohorts. First, we addressed CDAI and the prevalence of MetS in the general population; second, we explored the association between CDAI and mortality in patients with MetS by following NHANES 2001-2018 participants through December 31, 2019. In addition, restricted cubic spline (RCS), stratified analysis, and sensitivity analysis were used for further interpretation. We included 24,514 participants aged 20-85 years, in which the prevalence of MetS was 27.61 %. CDAI was negatively and dose-responsively associated with the prevalence of MetS, however it was not associated with mortality in patients with MetS. In addition, CDAI was associated with a reduced prevalence of certain components of MetS, including dyslipidemia and central obesity. RCS showed a linear correlation between CDAI and MetS and the above components. Stratified analyses indicated that alcohol consumption was a significant influence of CDAI-MetS and that socioeconomic status and lifestyle specificity existed. Sensitivity analysis confirmed the stability of the results. CDAI was protective against the development of MetS in the general population, but not against mortality in patients with MetS. Clinicians need to develop individualized prevention strategies to reduce the development of MetS by modifying CDAI.

Shanghai Community-Based Schizophrenia Cohort (SCS): a protocol for establishing a longitudinal cohort and research database of patients with schizophrenia receiving community-based mental health treatment.

INTRODUCTION: Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue. METHODS AND ANALYSIS: This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.

FTY720 Suppresses Pathogenic Retinal Müller Cell Activation and Chronic Progression by Inhibiting the mTOR/NF-κB Signaling Pathway and Regulating Autophagy.

PURPOSE: FTY720 is an agonist of the Sphingosine-1-phosphate (S1P) receptor 1, 3, 4, and 5 and a functional antagonist of the S1P1 receptor; it can inhibit the activation of mTOR/NF-κB and has therapeutic potential in inflammatory disease. This study was designed to determine the role of the inflammatory process in diabetic retinopathy and investigate the effect of FTY720 on high glucose (HG)-induced rat retinal Müller cells (rMC-1 cells). METHODS: In the present study, the role of FTY720 in inhibiting inflammation and its underlying mechanism were investigated. rMC-1 cells were treated without or with HG, FTY720, CQ, or RAP. Cell viability was examined by CCK-8 assay; cell activation was assessed by western blot analysis and IF staining; and cell migration was evaluated by a scratch wound healing assay. The expression of inflammation-associated proteins and autophagy-related proteins was evaluated by transmission electron microscopy, AO staining, MDC-labeled autophagic vacuoles, western blot analysis and ELISA. RESULTS: Western blot analysis and IF staining showed that the level of the rMC-1 cell marker GFAP was decreased, while GS was increased in FTY720 groups compared to that in the HG group. The healing assay results showed that compared with HG treatment, FTY720 treatment significantly reduced cell migration. Western blot analysis, ELISA and IF staining showed that compared with HG, FTY720 reduced proinflammatory proteins by inhibiting the mechanistic target of the mTOR/NF-κB signaling pathway and regulating autophagy. CONCLUSIONS: This study suggests that in an HG-induced rMC-1 cell model, FTY720 significantly inhibited the production of inflammatory cytokines by inhibiting mTOR/NF-κB signaling and regulating autophagy. These findings were associated with a decrease in rMC-1 cell injury, suggesting that FTY720 or related compounds may be valuable modulators of HG-induced retinal injury.

Controllable Blue Shift and Enhancement Emission during the Gradually Increasing Molecular Weight of Polyacrylamide.

Nonconventional luminescent polymers have become research hotspots due to their advantages such as persistent room temperature phosphorescence (p-RTP) emission and strong film-forming properties. It is proven that the molecular weight (MW) of such luminescent polymers has a significant impact on their emission over a large range, generally with a red shift as the MW increases. Herein, four controllable MW polyacrylamides are prepared via reversible addition-fragmentation chain transfer polymerization (RAFT), and their photoluminescence quantum yield and p-RTP lifetimes gradually increase with the increasing MW. The emission of p-RTP gradually shifts blue with increasing MW, which is likely due to the gradually changing interactions between the electron-rich portion in RAFT reagent and the increasing acrylamide (AM) units in the molecular chain. These can be reasonably explained through small angle X-ray scattering, the clustering-triggered emission (CTE) mechanism, and supported by theoretical calculations. Powder with controllable p-RTP capability has the potential for strategic anti-counterfeiting encryption. The above results not only promote the development of the CTE mechanism toward more precise explanations but also provide new ideas for the preparation of nonconventional luminescent polymers with controllable p-RTP emission performance.

Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Degradation of Poly(ethylene terephthalate) Catalyzed by Nonmetallic Dibasic Ionic Liquids under UV Radiation.

Nonmetallic ionic liquids (ILs) exhibit unique advantages in catalyzing poly (ethylene terephthalate) (PET) glycolysis, but usually require longer reaction times. We found that exposure to UV radiation can accelerate the glycolysis reaction and significantly reduce the reaction time. In this work, we synthesized five nonmetallic dibasic ILs, and their glycolysis catalytic activity was investigated. 1,8-diazabicyclo [5,4,0] undec-7-ene imidazole ([HDBU]Im) exhibited better catalytic performance. Meanwhile, UV radiation is used as a reinforcement method to improve the PET glycolysis efficiency. Under optimal conditions (5 g PET, 20 g ethylene glycol (EG), 0.25 g [HDBU]Im, 10,000 µW·cm-2 UV radiation reacted for 90 min at 185 °C), the PET conversion and BHET yield were 100% and 88.9%, respectively. Based on the UV-visible spectrum, it was found that UV radiation can activate the C=O in PET. Hence, the incorporation of UV radiation can considerably diminish the activation energy of the reaction, shortening the reaction time of PET degradation. Finally, a possible reaction mechanism of [HDBU]Im-catalyzed PET glycolysis under UV radiation was proposed.

Effects of clarithromycin exposure on the growth of Microcystis aeruginosa and the production of algal dissolved organic matter.

Antibiotics are commonly found in the aquatic environment, which can affect microbial community compositions and activities, and even have potential adverse impacts on human and ecosystem health. The current understanding of the effects of antibiotics on microalgae growth and algal dissolved organic matter (DOM) remains indistinct. To understand the toxic effects of antibiotics on the microalgae, Microcystis aeruginosa was exposed to clarithromycin (CLA) in this study. Cell density determination, chlorophyll content determination, and organic spectrum analysis were conducted to show the effect of CLA exposure on the growth, photosynthetic activity, and organic metabolic processes of Microcystis aeruginosa. The findings revealed that the physiological status of algae could be significantly influenced by CLA exposure in aquatic environments. Specifically, exposure to 1 µg/L CLA stimulated the growth and photosynthetic activity of algal cells. Conversely, CLA above 10 µg/L led to the inhibition of algal cell growth and photosynthesis. Notably, the inhibitory effects intensified with the increasing concentration of CLA. The molecular weight of DOM produced by Microcystis aeruginosa increased when exposed to CLA. Under the exposure of 60 µg/L CLA, a large number of algal cells ruptured and died, and the intracellular organic matter was released into the algal liquid. This resulted in an increase in high molecular weight substances and soluble microbial-like products in the DOM. Exposure to 1 and 10 µg/L CLA stimulated Microcystis aeruginosa to produce more humic acid-like substances, which may be a defense mechanism against CLA. The results were useful for assessing the effects of antibiotic pollution on the stability of the microalgae population and endogenous DOM characteristics in aquatic ecosystems.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Poly-l-lysine modified MOF nanoparticles with pH/ROS sensitive CIP release and CUR triggered photodynamic therapy against drug-resistant bacterial infection.

The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly-l-lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen (1O2) and superoxide anion radical (O2-) for efficient inhibition towards methicillin-resistant Staphylococcus aureus (MRSA). The charge conversion from negative charge (-4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H2O2, which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.

Proteasome-Associated Syndromes: Updates on Genetics, Clinical Manifestations, Pathogenesis, and Treatment.

The ubiquitin-proteasome system (UPS) has a critical role in post-translational protein modification that is essential for the maintenance of all cellular functions, including immune responses. The proteasome complex is ubiquitously expressed and is responsible for degradation of short-lived structurally abnormal, misfolded and not-needed proteins that are targeted for degradation via ubiquitin conjugation. Over the last 14 years, an increasing number of human diseases have been linked to pathogenic variants in proteasome subunits and UPS regulators. Defects of the proteasome complex or its chaperons - which have a regulatory role in the assembly of the proteasome - disrupt protein clearance and cellular homeostasis, leading to immune dysregulation, severe inflammation, and neurodevelopmental disorders in humans. Proteasome-associated diseases have complex inheritance, including monogenic, digenic and oligogenic disorders and can be dominantly or recessively inherited. In this review, we summarize the current known genetic causes of proteasomal disease, and discuss the molecular pathogenesis of these conditions based on the function and cellular expression of mutated proteins in the proteasome complex.

Targeted Ultrasound Nanobubbles Therapy for Prostate Cancer via Immuno-Sonodynamic Effect.

Background: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types. Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs' impact. Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells. Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.

Urinary cadmium levels in China (1982-2021): Regional trends and influential factors.

Despite the significant threat of cadmium exposure in China, a national-level assessment has been conspicuously absent. This study bridges this critical gap by collecting, geospatial analyzing and multivariable regression analyzing published studies on urinary cadmium levels in Chinese from 1982 to 2021. Our research reveals a notable decline trend in cadmium exposure among Chinese populations. However, this trend varies by region, age and gender group, higher levels are seen in the South (1.04 µg/g cr) compared to the North (0.48 µg/g cr), and in adults (1.08 µg/g cr) relative to children (0.33 µg/g cr), with higher levels being more pronounced in females (6.17 µg/g cr). Urinary cadmium is significantly correlated with rice consumption (P < 0.001), while mining activities have been identified as the dominant factor for cadmium exposure in most regions of China, a trend that is evident both in past decades and is expected to continue into the next decade. These findings underscore the need for region-specific environmental and public health strategies, designed to effectively address the distinct cadmium exposure risks in various regions and among different population groups, thus enhancing protection against the adverse effects of cadmium.

Construction of a ferroptosis and hypoxia-related gene signature in cervical cancer to assess tumour immune microenvironment and predict prognosis.

BACKGROUND: This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. METHODS: All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. RESULTS: Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. CONCLUSIONS: We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer.

Ferroptosis, hypoxia and immune regulation play important roles in cervical cancer progression. In this study, we developed a novel prognostic signature combining ferroptosis and hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer patients. The risk score established by ferroptosis and hypoxia-related gene as an independent prognostic factor of cervical cancer has a good survival prediction effect. High and low risk groups showed significant differences in TIME, prognosis, biological metabolic pathway and tumour mutation burden. In addition, we found drugs associated with signature genes. In short, this study has laid a theoretical foundation for exploring the related molecular mechanisms and prognosis of cervical cancer. It also contributes to the exploration of clinical management and treatment.

An Analysis of the Current Situation and Influence Factors of Narrative Competence Among Nurses in VIP Ward.

Objective: This study aimed to explore the proficiency level in medical narrative ability among nurses in VIP wards and identify the influencing factors. The objective was to provide valuable insights for enhancing the training and development of medical narrative skills among nurses in VIP wards, with the ultimate goal of promoting narrative nursing in clinical practice. Methods: A survey was conducted of 94 nurses working in VIP wards at a grade-A tertiary hospital in Zhongshan City, using the Narrative Competence Scale. Results: The findings revealed that nurses' overall medical narrative ability in VIP wards was relatively low, with a total score of (135.31±16.50). The primary factors identified as influential were professional titles and familiarity with narrative medicine or narrative nursing, which played significant roles. Specifically, nurses with higher professional titles demonstrated greater proficiency in medical storytelling. Moreover, nurses more familiar with narrative medicine or narrative nursing tended to exhibit higher levels of medical narrative ability. Conclusion: The results of this study highlight the significant opportunity for enhancing the medical narrative ability of nurses in VIP wards. To address this issue, it is recommended that training programs incorporate knowledge and skills related to narrative medicine and narrative nursing into the core competency development of VIP nurses. Additionally, there is a need to introduce narrative nursing practices gradually into clinical care. These measures will empower nurses to enhance their narrative abilities, providing superior nursing services to patients. Ultimately, such efforts will strengthen nurses' sense of professional value and increase the social benefits of nursing care.