Gut microbiome changes associated with chronic pancreatitis and pancreatic cancer: A systematic review and Meta-analysis.

BACKGROUND: The study of changes in the microbiome in chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) holds significant potential for developing noninvasive diagnostic tools as well as innovative interventions to alter the progression of diseases. This systematic review and meta-analysis aimed to analyze in detail the taxonomic and functional characteristics of the gut microbiome in patients with CP and PDAC. METHODS: Two researchers conducted a systematic search across public databases to gather all published research up to June 2023. Diversity and gut microbiota composition are the main outcomes we focus on. RESULTS: This meta-analysis included 14 studies, involving a total of 1511 individuals in the PDAC (n=285), CP (n=342), and control (n=649) groups. Our results show a significant difference in the composition of gut microbiota between PDAC/CP patients compared to healthy controls (HC), as evidenced by a slight decrease in α-diversity, including Shannon (SMD=-0.33; P=0.002 and SMD=-0.59; P<0.001, respectively) and a statistically significant ß-diversity (P<0.05). The pooled results showed that at the phylum level, the proportion of Firmicutes was lower in PDAC and CP patients than in HC patients. At the genus level, more than two studies demonstrated that 4 genera were significantly increased in PDAC patients compared to HC (e.g., Escherichia-Shigella and Veillonella). CP patients had an increase in 4 genera (e.g., Escherichia-Shigella and Klebsiella) and a decrease in 8 genera (e.g., Coprococcus and Bifidobacterium) compared to HC. Functional/metabolomics results from various studies also showed differences between PDAC/CP patients and HC. In addition, this study found no significant differences in gut microbiota between PDAC and CP patients. CONCLUSIONS: Current evidence suggests changes in gut microbiota is associated with PDAC/CP, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species. Further studies are needed to confirm these findings and explore therapeutic possibilities.

Performance of 18F-FDG PET/MRI and its parameters in staging and neoadjuvant therapy response evaluation in bladder cancer.

18F-FDG PET/MRI shows potential efficacy in the diagnosis of bladder cancer (BLCA). However, the performance of 18F-FDG PET/MRI in staging and neoadjuvant therapy (NAT) response evaluation for BLCA patients remains elusive. Here, we conduct this study to evaluate the performance of 18F-FDG PET/MRI and its derived parameters for tumor staging and NAT response prediction in BLCA. Forty BLCA patients were retrospectively enrolled to evaluate the performance of 18F-FDG PET/MRI in staging and NAT response prediction in BLCA. The feasibility of using 18F-FDG PET/MRI-related parameters for tumor staging and NAT response evaluation was also analyzed. In conclusion, 18F-FDG PET/MRI is found to show good performance in the BLCA staging and NAT response prediction. Moreover, ΔSUVmean is an efficacious candidate parameter for NAT response prediction. This study highlights that 18F-FDG PET/MRI is a promising imaging approach in the clinical diagnosis and treatment for BLCA.

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

ABSTRACT: Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 µSv h-1 after 13 min of shutdown meets the dose rate limit of 2.5 µSv h-1, at which point it is safe for workers to enter the treatment room area.

The significance of appendectomy in the context of colorectal cancer: impacts on gut microbiota and beyond.

Colorectal cancer (CRC) remains one of the most common malignancies globally, of which the initiative factors are multiple and complex. More recently, the major roles played by gut microbiota in the carcinogenesis of CRC have been uncovered, which indicates that dysbiosis caused by specific bacterial or fungal species may contribute to the malignant progression of CRC. Meanwhile, appendix, classically identified as an evolutionary relict with negligible physiological functions, has been found to play crucial roles in the immune modulation process and microbiome composition of gut by its lymphoid tissue features. In addition, appendectomy, a common surgical operation modality, has also been found to be closely correlated with the clinical outcomes of multiple diseases, including CRC. Naturally, these evidence collectively point to a possibility that the appendectomy may influence the pathological process of CRC through its impacts on gut microbiome.

The significance of appendectomy in the context of colorectal cancer: impacts on gut microbiota and beyond

Colorectal cancer (CRC) remains one of the most common malignancies globally, of which the initiative factors are multiple and complex. More recently, the major roles played by gut microbiota in the carcinogenesis of CRC have been uncovered, which indicates that dysbiosis caused by specific bacterial or fungal species may contribute to the malignant progression of CRC. Meanwhile, appendix, classically identified as an evolutionary relict with negligible physiological functions, has been found to play crucial roles in the immune modulation process and microbiome composition of gut by its lymphoid tissue features. In addition, appendectomy, a common surgical operation modality, has also been found to be closely correlated with the clinical outcomes of multiple diseases, including CRC. Naturally, these evidence collectively point to a possibility that the appendectomy may influence the pathological process of CRC through its impacts on gut microbiome. (AU)

Targeting MHC-I molecules for cancer: function, mechanism, and therapeutic prospects.

The molecules of Major histocompatibility class I (MHC-I) load peptides and present them on the cell surface, which provided the immune system with the signal to detect and eliminate the infected or cancerous cells. In the context of cancer, owing to the crucial immune-regulatory roles played by MHC-I molecules, the abnormal modulation of MHC-I expression and function could be hijacked by tumor cells to escape the immune surveillance and attack, thereby promoting tumoral progression and impairing the efficacy of cancer immunotherapy. Here we reviewed and discussed the recent studies and discoveries related to the MHC-I molecules and their multidirectional functions in the development of cancer, mainly focusing on the interactions between MHC-I and the multiple participators in the tumor microenvironment and highlighting the significance of targeting MHC-I for optimizing the efficacy of cancer immunotherapy and a deeper understanding of the dynamic nature and functioning mechanism of MHC-I in cancer.

ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape.

Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

Prognostic and immunological role of Asporin across cancers and exploration in bladder cancer.

BACKGROUND: Asporin (ASPN) has been identified as a player in tumorigenesis, but its precise roles and modulatory function are largely unknown. METHODS: In the present study, ASPN expression was first explored, followed by a prognostic evaluation of ASPN and a comprehensive investigation of the connections between ASPN and immunomodulation, immune cell infiltration and potential compounds on a pancancer level. Finally, ASPN expression was validated in bladder urothelial carcinoma (BLCA) tissues, and the potential function of ASPN, including its effects on migration and invasion capabilities, was investigated in tumor cells. RESULTS: The expression of ASPN exhibited significant variation across cancers and was found to be associated with patient prognosis. In addition, the expression level of APSN was markedly correlated with the abundances of infiltrating immune cells and cancer-associated fibroblasts and the expression levels of immunomodulatory genes based on the results of pancancer analysis. Metastasis and immune-associated signaling pathways were identified in enrichment analysis based on ASPN expression. Finally, we confirmed that ASPN expression increased with the degree of malignancy in BLCA tissues and cell lines and that low expression of ASPN hindered the migration and invasion of cells. CONCLUSIONS: ASPN has the potential to be a biomarker of cancer prognosis and a therapeutic target, and it also has predictive capability for the progression of BLCA.

Prediction of immune infiltration and prognosis for patients with urothelial bladder cancer based on the DNA damage repair-related genes signature.

Objectives: To analyze the correlations between the expression and effect of DNA damage repair genes and the immune status and clinical outcomes of urothelial bladder cancer (BLCA) patients. In addition, we evaluate the efficacy and value of utilizing the DNA damage repair genes signature as a prognosis model for BLCA. Methods: Two subtype groups (C1 and C2) were produced based on the varied expression of DNA damage repair genes. Significantly differentiated genes and predicted enriched gene pathways were obtained between the two subtypes. Seven key genes were obtained from the DNA damage repair-related genes and a 7-gene signature prognosis model was established based on the key genes. The efficacy and accuracy of this model in prognosis prediction was evaluated and verified in two independent databases. Also, the difference in biological functions, drug sensitivity, immune infiltration and affinity between the high-risk group and low-risk group was analyzed. Results: The DNA damage repair gene signature could significantly differentiate the BLCA into two molecular subgroups with varied genetic expression and enriched gene pathways. Seven key genes were screened out from the 232 candidate genes for prognosis prediction and a 7-gene signature prognosis model was established based on them. Two independent patient cohorts (TCGA cohort and GEO cohort) were utilized to validate the efficacy of the prognosis model, which demonstrated an effective capability to differentiate and predict the overall survival of BLCA patients. Also, the high-risk group and low-risk group derived from the 7-gene model exhibited significantly differences in drug sensitivity, immune infiltration status and biological pathways enrichment. Conclusions: Our established 7-gene signature model based on the DNA damage repair genes could serve as a novel prognosis predictive tool for BLCA. The differentiation of BLCA patients based on the 7-gene signature model may be of great value for the appropriate selection of specific chemotherapy agents and immune-checkpoint blockade therapy administration.

The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer.

Introduction: Bladder cancer (BLCA) is a highly malignant tumor of the urinary system, but the prognosis and survival rates have little improvement based on current therapeutic strategy. Immune checkpoint inhibitors (ICIs) therapy revolutionized the treatment of BLCA, but the clinical application of ICIs is limited by low response rate. Oxaliplatin (OXP), a second line chemotherapy drug for BLCA, may reshape the tumor immune microenvironment (TIME) via recruiting immune cells. Here, we conducted the study of oxaliplatin combined with anti-PD-1 inhibitor in BLCA mice models. Methods: The 6-8 weeks old female C57BL/6J mice were used to establish subcutaneous model of bladder tumor. After tumors developed, mice were given tail vein injections of PBS or oxaliplatin (2.5 mg/kg) and/or anti-PD-1 antibody (10 mg/kg). Tumor tissue samples and peripheral blood mononuclear cell (PBMC) were collected to systemically evaluate the efficiency and safety of combination OXP and anti-PD-1 inhibitor. The change of immune cells populations and the corresponding phenotypic diversity in TIME and PBMC were analysed by flow cytometry. Results: Tumor growth experiments clarified that the combination therapy was more efficient than medication alone. Flow cytometry analysis of tumor samples showed significant differences between untreated and treated mice. Oxaliplatin influences the TIME by increasing immune cells infiltration, including CD3+ T cells, CD4+ T cells, CD8+ T cells, dendritic cells (DC cells) and natural killer cells (NK cells). As for infiltrating cells, oxaliplatin upregulated the expression of CD134 and downregulated TIM-3 of CD4+ T cells, downregulated the PD-L1 expression of DC cells, which contributed to improve the anti-tumor effect and the treatment response of ICIs. Additionally, the evaluation of PBMC found that there were no significant changes in immune cell subsets and phenotypes, which validated the safety of the combination therapy. These results show the therapeutic potential for the combination of OXP and anti-PD-1 inhibitor in BLCA. Conclusion: OXP could increase the infiltration of immune cells in TIME to promote the anti-tumor activity of anti-PD-1 inhibitor. The present research provided an appropriate rationale of combination chemotherapy and immunotherapy therapy for BLCA.

Analysis and identification of the necroptosis landscape on therapy and prognosis in bladder cancer.

Bladder cancer (BLCA) is one of the most common malignant tumors of the urinary system, but the current therapeutic strategy based on chemotherapy and immune checkpoint inhibitor (ICI) therapy cannot meet the treatment needs, mainly owing to the endogenous or acquired apoptotic resistance of cancer cells. Targeting necroptosis provides a novel strategy for chemotherapy and targeted drugs and improves the efficacy of ICIs because of strong immunogenicity of necroptosis. Therefore, we systemically analyzed the necroptosis landscape on therapy and prognosis in BLCA. We first divided BLCA patients from The Cancer Genome Atlas (TCGA) database into two necroptosis-related clusters (C1 and C2). Necroptosis C2 showed a significantly better prognosis than C1, and the differential genes of C2 and C1 were mainly related to the immune response according to GO and KEGG analyses. Next, we constructed a novel necroptosis-related gene (NRG) signature consisting of SIRT6, FASN, GNLY, FNDC4, SRC, ANXA1, AIM2, and IKBKB to predict the survival of TCGA-BLCA cohort, and the accuracy of the NRG score was also verified by external datasets. In addition, a nomogram combining NRG score and several clinicopathological features was established to more accurately and conveniently predict the BLCA patient's survival. We also found that the NRG score was significantly related to the infiltration levels of CD8 T cells, NK cells, and iDC cells, the gene expression of CTLA4, PD-1, TIGIT, and LAG3 of TME, and the sensitivity to chemotherapy and targeted agents in BLCA patients. In conclusion, the NRG score has an excellent performance in evaluating the prognosis, clinicopathologic features, tumor microenvironment (TME), and therapeutic sensitivity of BLCA patients, which could be utilized as a guide for chemotherapy, ICI therapy, and combination therapy.

PLOD2 high expression associates with immune infiltration and facilitates cancer progression in osteosarcoma.

Background: Osteosarcoma (OS) is the most common primary malignant bone tumors in children and adolescents. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a key gene in mediating the formation of the stabilized collagen cross-link, playing an important role in the progression of cancer. However, the interaction between OS and PLOD2 has not been clarified so far. Methods: The target gene PLOD2 was screened through our own RNA-seq results and other two RNA-seq results from GEO database. The expression of PLOD2 in OS was detected by RT-qPCR, Western blot and immunohistochemistry. Functional experiments were performed to investigate the role of PLOD2 in OS cell invasion, migration and angiogenesis in vitro. An OS lung metastasis model was established to investigate the function of PLOD2 in OS metastasis and angiogenesis in vivo. The role of PLOD2 in immune infiltration in OS was explored by KEGG/GO analysis and immune infiltration analysis with TARGET, TCGA and TIMER. Results: PLOD2 was high-expressed in OS, which was related to poor prognosis of OS patients. PLOD2 promoted OS cell migration, invasion and angiogenesis in vitro and aggravated OS metastasis and angiogenesis in vivo. Bioinformatic analysis showed that PLOD2 played an important role in immune cell infiltration in OS, including CD8 positive T cells, macrophages M0 cells, DC cells, endothelial cells, iDC cells, ly endothelial cells, MEP cells, mv endothelial cells, native B cells, smooth muscle cells and Th1 cells. Immunohistochemical results showed that the expression of CD4 and CD8A was negatively correlated with the expression of PLOD2 in OS. Conclusion: PLOD2 was high-expressed in OS and promoted OS migration, invasion and angiogenesis in vitro and facilitated OS metastasis and angiogenesis in vivo. PLOD2 was associated with immune cell infiltration in OS, which could be a promising target to treat OS patients with metastasis and utilized to guide clinical immunotherapy in the future.

Antifungal immunity mediated by C-type lectin receptors may be a novel target in immunotherapy for urothelial bladder cancer.

Immunotherapies, such as immune-checkpoint blockade and adoptive T-cell therapy, offer novel treatment options with good efficacy for patients with urothelial bladder cancer. However, heterogeneity and therapeutic resistance have limited the use of immunotherapy. Further research into immune-regulatory mechanisms in bladder cancer is urgently required. Emerging evidence demonstrates that the commensal microbiota and its interactions with host immunity play pivotal roles in a variety of physiological and pathological processes, including in cancer. The gut microbiota has been identified as a potentially effective target of treatment that can be synergized with immunotherapy. The urothelial tract is also a key site for multiple microbes, although the immune-regulatory role of the urinary microbiome in the process of carcinogenesis of bladder cancer remains to be elucidated. We performed a comprehensive analysis of the expression and biological functions of C-type lectin receptors (CLRs), which have been recognized as innate pathogen-associated receptors for fungal microbiota, in bladder cancer. In line with previous research on fungal colonization of the urothelial tract, we found that CLRs, including Dectin-1, Dectin-2, Dectin-3, and macrophage-inducible Ca2+-dependent lectin receptor (Mincle), had a significant association with immune infiltration in bladder cancer. Multiple innate and adaptive pathways are positively correlated with the upregulation of CLRs. In addition, we found a significant correlation between the expression of CLRs and a range of immune-checkpoint proteins in bladder cancer. Based on previous studies and our findings, we hypothesize that the urinary mycobiome plays a key role in the pathogenesis of bladder cancer and call for more research on CLR-mediated anti-fungal immunity against bladder cancer as a novel target for immunotherapy in urothelial bladder cancer.

Spatial-temporal variations and pollution risks of mercury in water and sediments of urban lakes in Guangzhou City, South China.

This study aims to investigate the spatial and temporal characteristics, pollution degrees, and potential ecological risks of mercury (Hg) in urban lake waters and sediments in Guangzhou, where is a typical area of Hg emission and population-economic-industrial concentration in South China. In different districts of this city, the water from 15 lakes were collected continuously from June 2020 to May 2021, and the sediments from 9 lakes were collected in 2015 and 2021. The seasonal changes of Hg concentration (Hg-C) in the water were found to be high in winter and low in summer. The spatial distribution of Hg-C in sediments showed that it was high in urban central areas and low in suburbs. The Nemero index and geological accumulation index showed that there were uncontaminated of Hg in the collected lake water, and above moderately contaminated in the lake sediments in urban center, respectively. The Hg pollution potential ecological risk index showed that there was low risk in the collected water, high and extremely high risk in the lake sediments in urban center, respectively. The principal component analysis (PCA) and correlation analysis (CA) of Hg and meteorological factors showed that precipitation, temperature, and vapor pressure had negative effects on the seasonal changes of Hg-C in water, and air pressure and wind direction had positive effects. The PCA and CA of Hg and other geochemical elements showed that anthropogenic emissions may be the main sources of Hg in sediments, which was also supported by the data of population density, road density, and motor vehicles per 1000 people. This study provided a reference for urban lake pollution treatment, resident health, and ecological environment protection.

Evaluating adipose-derived stem cell exosomes as miRNA drug delivery systems for the treatment of bladder cancer.

OBJECTIVES: Exosomes are essential mediators of intercellular communication as they transport proteins and RNAs between cells. Owing to their tumor-targeting capacity, immune compatibility, low toxicity, and long half-life, mesenchymal stem cell-derived exosomes have great potential for the development of novel antitumor strategies. In this context, the role of exosomes produced by adipose-derived mesenchymal stem cells (ADSCs) for the treatment of bladder cancer (BC) remains unclear. Here, we investigated the use of ADSCs as a source of therapeutic exosomes, as well as their efficacy in delivering the tumor suppressor miR-138-5p in BC. METHODS: ADSCs stably expressing miR-138-5p were established using Lentivirus infection, and ADSC-derived miR-138-5p exosomes (Exo-miR-138-5p) were isolated from the cell culture medium. The effect of Exo-miR-138-5p on BC cell migration, invasion, and proliferation was evaluated in vitro using wound healing, transwell invasion, and proliferation assays. The in vivo effect of Exo-miR-138-5p was investigated using a subcutaneous xenograft mouse model. RESULTS: Exo-miR-138-5p prevented the migration, invasion, and proliferation of BC cells in vitro. Moreover, ADSC-derived exosomes could penetrate tumor tissues and successfully deliver miR-138-5p to suppress the growth of xenograft tumors in vivo. CONCLUSIONS: The present results reveal that ADSC-derived exosomes are an effective delivery vehicle for small molecule drugs in vivo, and exosome-delivered miR-138-5p is a promising therapeutic agent for BC treatment.

5-aminolevulinic acid-photodynamic therapy ameliorates cutaneous granuloma by killing drug-resistant Mycobacterium marinum.

BACKGROUND: Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) has been extensively used to treat various skin diseases, application for the treatment of cutaneous infection caused by Mycobacterium marinum (M. marinum), especially drug-resistant M. marinum, is unclear. OBJECTIVES: We evaluated the efficacy of ALA-PDT on M. marinum in a mouse infection model and tested its killing effect on M. marinum in vitro. We also investigated the clinical effect of ALA-PDT on cutaneous granuloma caused by drug-resistant M. marinum. MATERIALS AND METHODS: A total of 9 M. marinum strains isolated from patients were tested for anti-mycobacterial susceptibility. The effects of ALA-PDT on M. marinum in vitro and in mice model were investigated. Therapeutic efficacy was further assessed in two patients with cutaneous granuloma caused by drug- resistant M. marinum. RESULTS: We demonstrated that ALA-PDT directly killed M. marinum in vitro. The cutaneous lesions on mouse paws caused by M. marinum were fully recovered 4 weeks after the ALA-PDT treatment. ALA-PDT was also effective in two patients with cutaneous infection caused by drug-resistant M. marinum. The level of intracellular ROS in M. marinum treated with ALA-PDT was significantly higher than that of M. marinum alone. CONCLUSIONS: The results suggest that ALA-PDT is effective in treating M. marinum cutaneous infections by releasing more reactive oxygen species to kill M. marinum directly, and these effects are independent of systemic immune responses. The data highlights that ALA-PDT is a promising therapeutic choice for treatment of M. marinum cutaneous infections, especially drug-resistant M. marinum infections.

The Lymph Node Microenvironment May Invigorate Cancer Cells With Enhanced Metastatic Capacities.

Cancer metastasis, a typical malignant biological behavior involving the distant migration of tumor cells from the primary site to other organs, contributed majorly to cancer-related deaths of patients. Although constant efforts have been paid by researchers to elucidate the mechanisms of cancer metastasis, we are still far away from the definite answer. Recently, emerging evidence demonstrated that cancer metastasis is a continuous coevolutionary process mediated by the interactions between tumor cells and the host organ microenvironment, and epigenetic reprogramming of metastatic cancer cells may confer them with stronger metastatic capacities. The lymph node served as the first metastatic niche for many types of cancer, and the appearance of lymph node metastasis predicted poor prognosis. Importantly, multiple immune cells and stromal cells station and linger in the lymph nodes, which constitutes the complexity of the lymph node microenvironment. The active cross talk between cancer cells and immune cells could happen unceasingly within the metastatic environment of lymph nodes. Of note, diverse immune cells have been found to participate in the formation of malignant properties of tumor, including stemness and immune escape. Based on these available evidence and data, we hypothesize that the metastatic microenvironment of lymph nodes could drive cancer cells to metastasize to further organs through epigenetic mechanisms.

Quantifying the human disturbance intensity of ecosystems and its natural and socioeconomic driving factors in urban agglomeration in South China.

The impact of human activities on terrestrial ecosystems is becoming more intense than ever in history. Human disturbance analyses play important roles in appropriately managing the human-environment relationship. In this study, a human disturbance index (HDI) that uses land use and land cover data from 1980, 2000, 2010, and 2018 is proposed to assess the human disturbance of ecosystems in the Guangdong-Hong Kong-Macao Greater Bay Area. The HDI is first calculated by classifying the human disturbance intensity into seven levels and 13 categories from weak to strong in ecosystems. Then the driving factors of the HDI spatial pattern change are explored using a geographically weighted regression (GWR) model. The results showed that the spatial pattern of the HDI was high in the middle and low in the surrounding areas. The intensity of human disturbance increased, and the medium and high disturbance areas expanded during 1980-2018, especially in Guangzhou, Foshan, Shenzhen, and Dongguan. Human disturbance displayed an obvious spatial heterogeneity. The GWR model had a better explanation effect of the analysis of the HDI change drivers. The driving effect of the socioeconomic conditions was significantly stronger than that of the natural environmental. This study assists in understanding the distribution and change characteristics of the ecological environment in areas with strong human activities and provides a reference for related studies.