Analysis of clinical characteristics of mismatch repair status in colorectal cancer: a multicenter retrospective study.

BACKGROUND: Microsatellite instability (MSI) caused by DNA mismatch repair (MMR) deficiency is of great significance in the occurrence, diagnosis and treatment of colorectal cancer (CRC). AIM: This study aimed to analyze the relationship between mismatch repair status and clinical characteristics of CRC. METHODS: The histopathological results and clinical characteristics of 2029 patients who suffered from CRC and underwent surgery at two centers from 2018 to 2020 were determined. After screening the importance of clinical characteristics through machine learning algorithms, the patients were divided into deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) groups based on the immunohistochemistry results and the clinical feature data between the two groups were observed by statistical methods. RESULTS: The dMMR and pMMR groups had significant differences in histologic type, TNM stage, maximum tumor diameter, lymph node metastasis, differentiation grade, gross appearance, and vascular invasion. There were significant differences between the MLH1 groups in age, histologic type, TNM stage, lymph node metastasis, tumor location, and depth of invasion. The MSH2 groups were significantly different in age. The MSH6 groups had significant differences in age, histologic type, and TNM stage. There were significant differences between the PMS2 groups in lymph node metastasis and tumor location. CRC was dominated by MLH1 and PMS2 combined expression loss (41.77%). There was a positive correlation between MLH1 and MSH2 and between MSH6 and PMS2 as well. CONCLUSIONS: The proportion of mucinous adenocarcinoma, protruding type, and poor differentiation is relatively high in dMMR CRCs, but lymph node metastasis is rare. It is worth noting that the expression of MMR protein has different prognostic significance in different stages of CRC disease.

Estimating lead-attributable mortality burden by socioeconomic status in the USA.

BACKGROUND: This study aimed to estimate population-level and state-level lead-attributable mortality burdens stratified by socioeconomic status (SES) class in the USA. METHODS: Based on the National Health and Nutrition Examination Survey (NHANES), we constructed individual-level SES scores from income, employment, education and insurance data. We assessed the association between the blood lead levels (BLL) and all-cause mortality by Cox regression in the NHANES cohort (n = 31 311, 4467 deaths). With estimated hazard ratios (HR) and prevalences of medium (2-5 µg/dL) and high (≥ 5 µg/dL) BLL, we computed SES-stratified population-attributable fractions (PAFs) of all-cause mortality from lead exposure across 1999-2019. We additionally conducted a systematic review to estimate the lead-attributable mortality burden at state-level. RESULTS: The HR for every 2-fold increase in the BLL decreased from 1.23 (1.10-1.38) for the lowest SES class to 1.05 (0.90-1.23) for the highest SES class. Across all SES quintiles, medium BLL exhibited a greater mortality burden. Individuals with lower SES had higher lead-attributable burdens, and such disparities haver persisted over the past two decades. In 2017-19, annually 67 000 (32 000-112 000) deaths in the USA were attributable to lead exposure, with 18 000 (2000-41 000) of these deaths occurring in the lowest SES class. Substantial disparities in the state-level mortality burden attributable to lead exposure were also highlighted. CONCLUSIONS: These findings suggested that disparities in lead-attributable mortality burden persisted within US adults, due to heterogeneities in the effect sizes of lead exposure as well as in the BLL among different SES classes.

Highly efficient prevention of radiation dermatitis using a PEGylated superoxide dismutase dissolving microneedle patch.

PEGylated superoxide dismutase (PEG-SOD) is commonly used as a cytoprotective agent in radiotherapy. However, its effectiveness in preventing radiation dermatitis is limited owing to its poor skin permeability. To address this issue, a PEG-SOD-loaded dissolving microneedle (PSMN) patch was developed to effectively prevent radiation dermatitis. Initially, PSMN patches were fabricated using a template mold method with polyvinylpyrrolidone K90 as the matrix material. PSMNs exhibited a conical shape with adequate mechanical strength to penetrate the stratum corneum. More than 90 % of PEG-SOD was released from the PSMN patches within 30 min. Notably, the PSMN patches showed a significantly higher drug skin permeation than the PEG-SOD solutions, with a 500-fold increase. In silico simulations and experiments on skin pharmacokinetics confirmed that PSMN patches enhanced drug permeation and skin absorption, in contrast to PEG-SOD solutions. More importantly, PSMN patches efficiently mitigated ionizing radiation-induced skin damage, accelerated the healing process of radiation-affected skin tissues, and exhibited highly effective radioprotective activity for DNA in the skin tissue. Therefore, PSMN patches are promising topical remedy for the prevention of radiation dermatitis.

Bacterial imaging in tumour diagnosis.

Some bacteria, such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), have an inherent ability to locate solid tumours, making them a versatile platform that can be combined with other tools to improve the tumour diagnosis and treatment. In anti-cancer therapy, bacteria function by carrying drugs directly or expressing exogenous therapeutic genes. The application of bacterial imaging in tumour diagnosis, a novel and promising research area, can indeed provide dynamic and real-time monitoring in both pre-treatment assessment and post-treatment detection. Different imaging techniques, including optical technology, acoustic imaging, magnetic resonance imaging (MRI) and nuclear medicine imaging, allow us to observe and track tumour-associated bacteria. Optical imaging, including bioluminescence and fluorescence, provides high-sensitivity and high-resolution imaging. Acoustic imaging is a real-time and non-invasive imaging technique with good penetration depth and spatial resolution. MRI provides high spatial resolution and radiation-free imaging. Nuclear medicine imaging, including positron emission tomography (PET) and single photon emission computed tomography (SPECT) can provide information on the distribution and dynamics of bacterial population. Moreover, strategies of synthetic biology modification and nanomaterial engineering modification can improve the viability and localization ability of bacteria while maintaining their autonomy and vitality, thus aiding the visualization of gut bacteria. However, there are some challenges, such as the relatively low bacterial abundance and heterogeneously distribution within the tumour, the high dimensionality of spatial datasets and the limitations of imaging labeling tools. In summary, with the continuous development of imaging technology and nanotechnology, it is expected to further make in-depth study on tumour-associated bacteria and develop new bacterial imaging methods for tumour diagnosis.

Third-generation PacBio sequencing to explore gut bacteria and gender in colorectal cancer.

BACKGROUND: Gut bacteria have an important influence on colorectal cancer (CRC). The differences of gut bacteria between genders have been the hot spots. OBJECTIVE: To analyze the relationship between gut bacteria and gender differences in patients with CRC. METHODS: A total of 212 patients with CRC and 212 healthy volunteers were recruited. The subjects' fecal samples were obtained, and the fecal microorganisms were analyzed by the third-generation sequencing PacBio. The composition of gut bacteria was analyzed. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the differences in gut bacteria. Pearson coefficient was used to calculate the correlation between differential bacteria. CRC risk prediction models were used to rank the importance of effective differential bacteria. RESULTS: Escherichia flexneri and Phocaeicola vulgatus were the most frequent bacteria in both male and female CRC patients. Bacteroides, Verrucomicrobia and Akkermansiaceae were highly enriched in male CRC group, while Bacteroidetes, Phocaeicola and Tissierellales were highly enriched in female CRC group. Peptostreptococcus anaerobius and Phocaeicola vulgatus were important CRC related bacteria in males and females, respectively. Peptostreptococcus anaerobius was the most important characteristic bacterium of males (AUC = 0.951), and the sensitivity and specificity of the discovery set were 78.74 % and 93.98 %, respectively. Blautia stercoris was the most important characteristic bacterium of females (AUC = 0.966), and the sensitivity and specificity of the discovery set were 90.63 % and 90.63 %, respectively. CONCLUSION: Gut bacteria varied in different genders. Therefore, gender should be considered when gut bacteria are applied in the diagnose and prevention of CRC.

Tislelizumab combined with GT chemotherapy for intimal sarcoma of inferior vena cava: A case report.

RATIONALE: Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods. PATIENT CONCERNS: A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital. DIAGNOSES: The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG. INTERVENTIONS: The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation). OUTCOMES: The disease was stabilized after receiving the treatment. LESSONS: Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.

Aging Gut Microbiome in Healthy and Unhealthy Aging.

The characteristics of human aging manifest in tissue and organ function decline, heightening susceptibility to age-related ailments, thereby presenting novel challenges to fostering and sustaining healthy longevity. In recent years, an abundance of research on human aging has surfaced. Intriguingly, evidence suggests a pervasive correlation among gut microbiota, bodily functions, and chronic diseases. From infancy to later stages of adulthood, healthy individuals witness dynamic shifts in gut microbiota composition. This microbial community is associated with tissue and organ function deterioration (e.g., brain, bones, muscles, immune system, vascular system) and heightened risk of age-related diseases. Thus, we present a narrative review of the aging gut microbiome in both healthy and unhealthy aging contexts. Additionally, we explore the potential for adjustments to physical health based on gut microbiome analysis and how targeting the gut microbiome can potentially slow down the aging process.

Advances in single-cell sequencing technology in microbiome research.

With the rapid development of histological techniques and the widespread application of single-cell sequencing in eukaryotes, researchers desire to explore individual microbial genotypes and functional expression, which deepens our understanding of microorganisms. In this review, the history of the development of microbial detection technologies was revealed and the difficulties in the application of single-cell sequencing in microorganisms were dissected as well. Moreover, the characteristics of the currently emerging microbial single-cell sequencing (Microbe-seq) technology were summarized, and the prospects of the application of Microbe-seq in microorganisms were distilled based on the current development status. Despite its mature development, the Microbe-seq technology was still in the optimization stage. A retrospective study was conducted, aiming to promote the widespread application of single-cell sequencing in microorganisms and facilitate further improvement in the technology.

Transcriptional profile and immune infiltration in colorectal cancer reveal the significance of inducible T-cell costimulator as a crucial immune checkpoint molecule.

BACKGROUND: Emergence of novel immuno-therapeutics has shown promising improvement in the clinical outcome of colorectal cancer (CRC). OBJECTIVE: To identify robust immune checkpoints based on expression and immune infiltration profiles of clinical CRC samples. METHODS: One dataset from The Cancer Genome Atlas database and two from Gene Expression Omnibus were independently employed for the analysis. Genes associated with overall survival were identified, and distribution of each immune checkpoint with respect to different clinical features was determined to explore key immune checkpoints. Multiple staining methods were used to verify the correlation between key immune checkpoint ICOS and clinical pathological features. Differentially expressed mRNA and long non-coding RNA (lncRNA) were then detected for gene set enrichment analysis and gene set variation analysis to investigate the differentially enriched biological processes between low- and high-expression groups. Significant immune-related mRNAs and lncRNA were subjected to competing endogenous RNA (ceRNA) network analysis. Correlation of inducible T-cell costimulator (ICOS) and top 10 genes in ceRNA network were further considered for validation. RESULTS: ICOS was identified from 14 immune checkpoints as the most highly correlated gene with survival and clinical features in CRC. The expression of ICOS protein in the poorly differentiated group was lower than that in the moderately differentiated group, and the expression in different pathological stages was significant. In addition, the expressions of ICOS were negatively correlated with Ki67. A conspicuous number of immune-related pathways were enriched in differentially expressed genes in the ICOS high- and low-expression groups. Integration with immune infiltration data revealed a multitude of differentially expressed immune-related genes enriched for ceRNA network. Furthermore, expression of top 10 genes investigated from ceRNA network showed high correlation with ICOS. CONCLUSION: ICOS might serve as a robust immune checkpoint for prognosis with several genes being potential targets of ICOS-directed immunotherapy in CRC.

CFViSA: A comprehensive and free platform for visualization and statistics in omics-data.

INTRODUCTION: The rapid growth of omics technologies has led to the use of bioinformatics as a powerful tool for unravelling scientific puzzles. However, the obstacles of bioinformatics are compounded by the complexity of data processing and the distinct nature of omics data types, particularly in terms of visualization and statistics. OBJECTIVES: We developed a comprehensive and free platform, CFViSA, to facilitate effortless visualization and statistical analysis of omics data by the scientific community. METHODS: CFViSA was constructed using the Scala programming language and utilizes the AKKA toolkit for the web server and MySQL for the database server. The visualization and statistical analysis were performed with the R program. RESULTS: CFViSA integrates two omics data analysis pipelines (microbiome and transcriptome analysis) and an extensive array of 79 analysis tools spanning simple sequence processing, visualization, and statistics available for various omics data, including microbiome and transcriptome data. CFViSA starts from an analysis interface, paralleling a demonstration full course to help users understand operating principles and scientifically set the analysis parameters. Once analysis is conducted, users can enter the task history interface for figure adjustments, and then a complete series of results, including statistics, feature tables and figures. All the graphic layouts were printed with necessary statistics and a traceback function recording the options for analysis and visualization; these statistics were excluded from the five competing methods. CONCLUSION: CFViSA is a user-friendly bioinformatics cloud platform with detailed guidelines for integrating functions in multi-omics analysis with real-time visualization adjustment and complete series of results provision. CFViSA is available at http://www.cloud.biomicroclass.com/en/CFViSA/.

Classification of Colorectal Cancer Subtypes Based on Endoplasmic Reticulum Stress.

INTRODUCTION: Endoplasmic reticulum stress (ERS) is associated with the occurrence and development of colorectal cancer (CRC). METHODS: One thousand nine CRC samples and 3 ERS gene sets from GEO database were used to screen and validate genes related to stage and prognosis of CRC. Twenty thousand five hundred thirty samples from the TCGA database validated the ERS genes related to prognosis. PPI network construction and coexpression analysis were used to investigate the correlation of genes. ConsensusClusterPlus analysis was used to classify CRC subtypes. Cox regression and the LASSO algorithm were used to screen ERS genes related to prognosis. HE staining, immunohistochemical staining, and RT-qPCR of 50 owner-central samples were used to verify the genes. The ERscore model was constructed based on the ERS genes related to prognosis. The nomogram model was used to verify that different subtypes of CRC patients have different prognosis. RESULTS: Fifty ERS differentially expressed genes related to CRC stage and 8 ERS model genes related to prognosis were screened. Three subtypes of CRC were classified based on the former 50 genes. The clinical characteristics were significantly different among the subtypes. The ERscore model was constructed based on the latter 8 genes, and its accuracy was verified by clinical samples. Finally, the nomogram was constructed based on ERscore, age, and CRC stage, and the accuracy of the nomogram prediction was verified. CONCLUSION: ERS-related genes can be used as classification criteria for CRC, and the related clinical characteristics of different CRC subtypes are different.

STAB2: an updated spatio-temporal cell atlas of the human and mouse brain.

The brain is constituted of heterogeneous types of neuronal and non-neuronal cells, which are organized into distinct anatomical regions, and show precise regulation of gene expression during development, aging and function. In the current database release, STAB2 provides a systematic cellular map of the human and mouse brain by integrating recently published large-scale single-cell and single-nucleus RNA-sequencing datasets from diverse regions and across lifespan. We applied a hierarchical strategy of unsupervised clustering on the integrated single-cell transcriptomic datasets to precisely annotate the cell types and subtypes in the human and mouse brain. Currently, STAB2 includes 71 and 61 different cell subtypes defined in the human and mouse brain, respectively. It covers 63 subregions and 15 developmental stages of human brain, and 38 subregions and 30 developmental stages of mouse brain, generating a comprehensive atlas for exploring spatiotemporal transcriptomic dynamics in the mammalian brain. We also augmented web interfaces for querying and visualizing the gene expression in specific cell types. STAB2 is freely available at https://mai.fudan.edu.cn/stab2.

Application of roadside air purifiers in urban street canyons: A pilot-scale study in Hong Kong.

The implementation of roadside air purifiers has emerged as an effective active control measure to alleviate air pollution in urban street canyons. However, technical questions raised under real conditions remain challenging. In this study, we conducted a pilot-scale investigation involving seven units of self-designed roadside air purifiers in an urban street canyon in Hong Kong. The air cleaning effects were quantified with an air quality sensor network after rigorous quality control. The removal efficiencies of Nitrogen dioxide (NO2), Fine suspended particulates (PM2.5), Carbon monoxide (CO), and Nitric oxide (NO) were determined by comparing with simultaneously measured ambient concentrations, with hourly average efficiencies of 14.0 %-16.9 %, 3.5-10.0 %, 11.9 %-18.7 %, and 19.2 %-44.9 %, respectively. Generally, the purification effects presented variations depending on the ambient pollutants' levels. Higher ambient concentrations of NO2, PM2.5, CO correlated with increased purification effects, while NO presented the opposite trend. The influence of interval distance combined with spatial distribution indicated the operation of purifiers will induce local NO2 attenuation even at an interval distance of four meters. Statistical analysis delivered evidence the air cleaning ability exhibited optimal performance when relative humidity level is ranged from 70 % to 90 %, aligning with the prevailing conditions in Hong Kong. Additionally, improved purification effects were observed at the downwind direction, and their performance was enhanced when the wind speed exceeded 2.5 m/s. Moreover, we estimated the operational lifetime of the air purifiers to be approximately 130 days, offering crucial information regarding the filter replacement cycle. This work serves as a pioneering case study, showcasing the feasibility and deployment considerations of roadside air purifiers in effectively controlling air pollution in urban environments.

Advances in immunotyping of colorectal cancer.

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies.

Single-cell transcriptome analysis reveals T population heterogeneity and functions in tumor microenvironment of colorectal cancer metastases.

Cell mediated immune escape, a microenvironment factor, induces tumorigenesis and metastasis. The purpose of this study was to display the characteristics of T cell populations in immune microenvironments for colorectal cancer (CRC) metastasis. Unsupervised cluster analysis was conducted to identify functionally distinct T cell clusters from 3,003 cells in peripheral blood and 4,656 cells in tissues. Subsequently, a total of 8 and 4 distinct T cell population clusters were identified from tumor tissue and peripheral blood, respectively. High levels of CD8+TEX, CD4+TRM, TH1-like T cells, CD8+TEM, tumor-Treg from tissues, and CD4+TN from peripheral blood are essential components of immune microenvironment for the prediction of CRC metastasis. Moreover, exhausted T cells are characterized by higher expression of multiple inhibitory receptors, including PDCD1 and LAG3. Some genes such as PFKFB3, GNLY, circDCUN1D4, TXNIP and NR4A2 in T cells of cluster were statistically different between CRC metastasis and non-metastasis. The ligand-receptor interactions identified between different cluster cells and metastases-related DEGs identified from each cluster revealed that the communications of cells, alterations of functions, and numbers of T subsets may contribute to the metastasis of CRC. The mutation frequency of KiAA1551, ATP8B4 and LNPEP in T cells from tissues and SOR1 from peripheral blood were higher in metastatic CRC than that in non-metastatic CRC. In conclusion, the discovery of differential genes in T cells may provide potential targets for immunotherapy of CRC metastasis and relevant insights into the clinical prediction and prognosis of CRC metastasis.

Aging characteristics of colorectal cancer based on gut microbiota.

BACKGROUND: Aging is one of the factors leading to cancer. Gut microbiota is related to aging and colorectal cancer (CRC). METHODS: A total of 11 metagenomic data sets related to CRC were collected from the R package curated Metagenomic Data. After batch effect correction, healthy individuals and CRC samples were divided into three age groups. Ggplot2 and Microbiota Process packages were used for visual description of species composition and PCA in healthy individuals and CRC samples. LEfSe analysis was performed for species relative abundance data in healthy/CRC groups according to age. Spearman correlation coefficient of age-differentiated bacteria in healthy individuals and CRC samples was calculated separately. Finally, the age prediction model and CRC risk prediction model were constructed based on the age-differentiated bacteria. RESULTS: The structure and composition of the gut microbiota were significantly different among the three groups. For example, the abundance of Bacteroides vulgatus in the old group was lower than that in the other two groups, the abundance of Bacteroides fragilis increased with aging. In addition, seven species of bacteria whose abundance increases with aging were screened out. Furthermore, the abundance of pathogenic bacteria (Escherichia_coli, Butyricimonas_virosa, Ruminococcus_bicirculans, Bacteroides_fragilis and Streptococcus_vestibularis) increased with aging in CRCs. The abundance of probiotics (Eubacterium_eligens) decreased with aging in CRCs. The age prediction model for healthy individuals based on the 80 age-related differential bacteria and model of CRC patients based on the 58 age-related differential bacteria performed well, with AUC of 0.79 and 0.71, respectively. The AUC of CRC risk prediction model based on 45 disease differential bacteria was 0.83. After removing the intersection between the disease-differentiated bacteria and the age-differentiated bacteria from the healthy samples, the AUC of CRC risk prediction model based on remaining 31 bacteria was 0.8. CRC risk prediction models for each of the three age groups showed no significant difference in accuracy (young: AUC=0.82, middle: AUC=0.83, old: AUC=0.85). CONCLUSION: Age as a factor affecting microbial composition should be considered in the application of gut microbiota to predict the risk of CRC.

Pancreatic follicular dendritic cell sarcoma: a rare case report and systematic literature review of 7 cases.

INTRODUCTION: Pancreatic follicular dendritic cell sarcoma (FDCS) is an exceptionally rare and low-to-moderate malignancy, with only seven reported cases to date. Clinical diagnosis of FDCS is challenging due to the lack of distinct biological and radiographic features. CASE PRESENTATION: A 67-year-old woman presented to the hospital with a 4-day history of severe abdominal pain. Imaging studies (CT and MRI) revealed a large cystic mass located at the tail of the pancreas, which was suspected to be myeloid sarcoma (MS) based on EUS and CT-guided pancreatic puncture. Postoperative pathology and immunohistochemistry confirmed the diagnosis of pancreatic FDCS. After the diagnosis was confirmed, the patient received postoperative chemotherapy with the CHOP regimen. At 11 months of follow-up, there was no evidence of recurrence. Seven published cases have been reviewed to comprehensively summarize the clinical characteristics, diagnosis, and treatment options of FDCS. CONCLUSION: While imaging can be useful in detecting pancreatic FDCS, it should be interpreted with caution as it can be challenging to differentiate from other pancreatic tumors. Pathology and immunohistochemistry are considered the gold standard for diagnosis, with CD21, CD23, and CD35 being specific tumor cell markers. However, preoperative diagnosis of pancreatic FDCS remains difficult, and the pancreatic puncture may further increase the risk of misdiagnosis. The disease is highly prone to recurrence and metastasis, and surgery is the preferred method for both diagnosis and treatment of localized disease.

Comprehensive Assessment of Pollution Sources and Health Impacts in Suburban Area of Shanghai.

Shanghai, one of China's largest metropolises, faces significant environmental pollution challenges due to rapid economic development. Suburban areas of Shanghai are affected by both long-distance transport and local sources of pollutants. This study conducted an integrated analysis that links health-risk assessment of heavy metals and source apportionment of atmospheric constituents to distinguish the contributions of emission sources and the major sources of health risks. Source-apportionment analysis revealed that secondary sources had the greatest contribution to the local pollutants, indicating the significant influence of peripheral and long-distance transport. Health-risk assessment of Cr, Ni, As, and Cd revealed that local residents were exposed to respiratory health risks, in which Cr is the major contributor. This health risk was primarily associated with emissions from nearby industry-related sources. Our study highlights the significant effects of both long-distance transport and local source emissions on atmospheric composition and human health in large urban agglomerations. The findings can inform future efforts to develop more precise emission-reduction strategies and policy improvements to mitigate environmental pollution and protect public health.