Microenvironment-Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair.

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair.

A Multifunctional Nanoreactor-Induced Dual Inhibition of HSP70 Strategy for Enhancing Mild Photothermal/Chemodynamic Synergistic Tumor Therapy.

Mild photothermal therapy (PTT) is a spatiotemporally controllable method that utilizes the photothermal effect at relatively low temperatures (40-45 °C) to especially eliminate tumor tissues with negligible side effects on the surrounding normal tissues. However, the overexpression of heat shock protein 70 (HSP70) and limited effect of single treatment drastically impede the therapeutic efficacy. Herein, the constructed multifunctional core-shell structured Ag-Cu@SiO2-PDA/GOx nanoreactors (APG NRs) that provide a dual inhibition of HSP70 strategy for the second near-infrared photoacoustic (NIR-II PA) imaging-guided combined mild PTT/chemodynamic therapy (CDT). The Ag-Cu cores can convert endogenous H2O2 to hydroxyl radical (•OH), which can induce lipid peroxidation (LPO) and further degrade HSP70. The polydopamine (PDA)/glucose oxidase (GOx) shells are utilized as the NIR-II photothermal agent to generate low temperature, and the GOx can reduce the energy supplies and inhibit energy-dependent HSP70 expression. Furthermore, both the generation of •OH and GOx-mediated energy shortage can reduce HSP70 expression to sensitize mild PTT under 1064 nm laser, and in turn, GOx and laser self-amplify the catalytic reactions of APG NRs for more production of •OH. The multifunctional nanoreactors will provide more potential possibilities for the clinical employment of mild PTT and the advancement of tumor combination therapies.

PIPET: predicting relevant subpopulations in single-cell data using phenotypic information from bulk data.

Single-cell RNA sequencing has revealed cellular heterogeneity in complex tissues, notably benefiting research on diseases such as cancer. However, the integration of single-cell data from small samples with extensive clinical features in bulk data remains underexplored. In this study, we introduce PIPET, an algorithmic method for predicting relevant subpopulations in single-cell data based on multivariate phenotypic information from bulk data. PIPET generates feature vectors for each phenotype from differentially expressed genes in bulk data and then identifies relevant cellular subpopulations by assessing the similarity between single-cell data and these vectors. Subsequently, phenotype-related cell states can be analyzed based on these subpopulations. In simulated datasets, PIPET showed robust performance in predicting multiclassification cellular subpopulations. Application of PIPET to lung adenocarcinoma single-cell RNA sequencing data revealed cellular subpopulations with poor survival and associations with TP53 mutations. Similarly, in breast cancer single-cell data, PIPET identified cellular subpopulations associated with the PAM50 clinical subtypes and triple-negative breast cancer subtypes. Overall, PIPET effectively identified relevant cellular subpopulations in single-cell data, guided by phenotypic information from bulk data. This approach comprehensively delineates the molecular characteristics of each cellular subpopulation, offering insights into disease-related subpopulations and guiding personalized treatment strategies.

NIR-II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.

Decoding trends in mRNA vaccine research: A comprehensive bibliometric study.

BACKGROUND: In recent years, infectious diseases like COVID-19 have had profound global socio-economic impacts. mRNA vaccines have gained prominence due to their rapid development, industrial adaptability, simplicity, and responsiveness to new variants. Notably, the 2023 Nobel Prize in Physiology or Medicine recognized significant contributions to mRNA vaccine research. METHODS: Our study employed a comprehensive bibliometric analysis using the Web of Science Core Collection (WoSCC) database, encompassing 5,512 papers on mRNA vaccines from 2003 to 2023. We generated cooperation maps, co-citation analyses, and keyword clustering to evaluate the field's developmental history and achievements. RESULTS: The analysis yielded knowledge maps highlighting countries/institutions, influential authors, frequently published and highly cited journals, and seminal references. Ongoing research hotspots encompass immune responses, stability enhancement, applications in cancer prevention and treatment, and combating infectious diseases using mRNA technology. CONCLUSIONS: mRNA vaccines represent a transformative development in infectious disease prevention. This study provides insights into the field's growth and identifies key research priorities, facilitating advancements in vaccine technology and addressing future challenges.

Integrative single-cell analysis of LUAD: elucidating immune cell dynamics and prognostic modeling based on exhausted CD8+ T cells.

Background: The tumor microenvironment (TME) plays a pivotal role in the progression and metastasis of lung adenocarcinoma (LUAD). However, the detailed characteristics of LUAD and its associated microenvironment are yet to be extensively explored. This study aims to delineate a comprehensive profile of the immune cells within the LUAD microenvironment, including CD8+ T cells, CD4+ T cells, and myeloid cells. Subsequently, based on marker genes of exhausted CD8+ T cells, we aim to establish a prognostic model for LUAD. Method: Utilizing the Seurat and Scanpy packages, we successfully constructed an immune microenvironment atlas for LUAD. The Monocle3 and PAGA algorithms were employed for pseudotime analysis, pySCENIC for transcription factor analysis, and CellChat for analyzing intercellular communication. Following this, a prognostic model for LUAD was developed, based on the marker genes of exhausted CD8+ T cells, enabling effective risk stratification in LUAD patients. Our study included a thorough analysis to identify differences in TME, mutation landscape, and enrichment across varying risk groups. Moreover, by integrating risk scores with clinical features, we developed a new nomogram. The expression of model genes was validated via RT-PCR, and a series of cellular experiments were conducted, elucidating the potential oncogenic mechanisms of GALNT2. Results: Our study developed a single-cell atlas for LUAD from scRNA-seq data of 19 patients, examining crucial immune cells in LUAD's microenvironment. We underscored pDCs' role in antigen processing and established a Cox regression model based on CD8_Tex-LAYN genes for risk assessment. Additionally, we contrasted prognosis and tumor environments across risk groups, constructed a new nomogram integrating clinical features, validated the expression of model genes via RT-PCR, and confirmed GALNT2's function in LUAD through cellular experiments, thereby enhancing our understanding and approach to LUAD treatment. Conclusion: The creation of a LUAD single-cell atlas in our study offered new insights into its tumor microenvironment and immune cell interactions, highlighting the importance of key genes associated with exhausted CD8+ T cells. These discoveries have enabled the development of an effective prognostic model for LUAD and identified GALNT2 as a potential therapeutic target, significantly contributing to the improvement of LUAD diagnosis and treatment strategies.

Advances in Engineered Macrophages: A New Frontier in Cancer Immunotherapy.

Macrophages, as pivotal cells within the tumour microenvironment, significantly influence the impact of and reactions to treatments for solid tumours. The rapid evolution of bioengineering technology has revealed the vast potential of engineered macrophages in immunotherapy, disease diagnosis, and tissue engineering. Given this landscape, the goal of harnessing and innovating macrophages as a novel strategy for solid tumour immunotherapy cannot be overstated. The diverse strategies for engineered macrophages in the realm of cancer immunotherapy, encompassing macrophage drug delivery systems, chimeric antigen receptor macrophage therapy, and synergistic treatment approaches involving bacterial outer membrane vesicles and macrophages, are meticulously examined in this review. These methodologies are designed to enhance the therapeutic efficacy of macrophages against solid tumours, particularly those that are drug-resistant and metastatic. Collectively, these immunotherapies are poised to supplement and refine current solid tumour treatment paradigms, thus heralding a new frontier in the fight against malignant tumours.

LRRK2 G2019S Promotes Colon Cancer Potentially via LRRK2-GSDMD Axis-Mediated Gut Inflammation.

Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine protein kinase belonging to the ROCO protein family. Within the kinase domain of LRRK2, a point mutation known as LRRK2 G2019S has emerged as the most prevalent variant associated with Parkinson's disease. Recent clinical studies have indicated that G2019S carriers have an elevated risk of cancers, including colon cancer. Despite this observation, the underlying mechanisms linking LRRK2 G2019S to colon cancer remain elusive. In this study, employing a colitis-associated cancer (CAC) model and LRRK2 G2019S knock-in (KI) mouse model, we demonstrate that LRRK2 G2019S promotes the pathogenesis of colon cancer, characterized by increased tumor number and size in KI mice. Furthermore, LRRK2 G2019S enhances intestinal epithelial cell proliferation and inflammation within the tumor microenvironment. Mechanistically, KI mice exhibit heightened susceptibility to DSS-induced colitis, with inhibition of LRRK2 kinase activity ameliorating colitis severity and CAC progression. Our investigation also reveals that LRRK2 G2019S promotes inflammasome activation and exacerbates gut epithelium necrosis in the colitis model. Notably, GSDMD inhibitors attenuate colitis in LRRK2 G2019S KI mice. Taken together, our findings offer experimental evidence indicating that the gain-of-kinase activity in LRRK2 promotes colorectal tumorigenesis, suggesting LRRK2 as a potential therapeutic target in colon cancer patients exhibiting hyper LRRK2 kinase activity.

Recent advancements in mogrosides: A review on biological activities, synthetic biology, and applications in the food industry.

Mogrosides are low-calorie, biologically active sweeteners that face high production costs due to strict cultivation requirements and the low yield of monk fruit. The rapid advancement in synthetic biology holds the potential to overcome this challenge. This review presents mogrosides exhibiting antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and liver protective activities, with their efficacy in diabetes treatment surpassing that of Xiaoke pills (a Chinese diabetes medication). It also discusses the latest elucidated biosynthesis pathways of mogrosides, highlighting the challenges and research gaps in this field. The critical and most challenging step in this pathway is the transformation of mogrol into a variety of mogrosides by different UDP-glucosyltransferases (UGTs), primarily hindered by the poor substrate selectivity, product specificity, and low catalytic efficiency of current UGTs. Finally, the applications of mogrosides in the current food industry and the challenges they face are discussed.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

BACKGROUND: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. METHODS: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. RESULTS: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. CONCLUSION: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Targeting neutrophils: Mechanism and advances in cancer therapy.

BACKGROUND: Cancer is a thorny problem which cannot be conquered by mankind at present and recent researchers have put their focus on tumor microenviroment. Neutrophils, the prominent leukocytes in peripheral blood that accumulate in tumours, serves as frontline cells in response to tumour progression owing to the rapid development of micro biotechnology. Hence, targeted therapy with these neutrophils has made targeting treatment a promising field in cancer therapy. MAIN BODY: We broadly summarise some studies on the phenotypes and functions of tumour-associated neutrophils as well as the unique web-like products of neutrophils that play a role in cancer progression-neutrophil extracellular traps-and the interactions between neutrophils and the tumour microenvironment. Moreover, several targeted neutrophils therapeutic studies have made some progress and provided potential strategies for the treatment of cancer. CONCLUSION: This review aims to offer a holistic perspective on therapeutic interventions targeting neutrophils to further inspire more researches on cancer therapies.

DFT Study of Metal (Ag, Au, Pt)-Modified SnS2 for Adsorption of SF6 Decomposition Gases in Gas-Insulated Switchgear.

In this study, the gas-sensitive response of metal (Ag, Au, Pt)-modified SnS2 toward SF6 decomposition gases (SOF2, SO2F2, SO2, H2S) in gas-insulated switchgear was studied by analyzing the adsorption structure, band structure, charge transfer, and density of states based on density functional theory. The results show that the adsorption of the four target gases on pristine SnS2 belongs to weak physical adsorption. Compared with the pristine SnS2, the adsorption energy of the transition metal atom-modified SnS2 monolayer has been improved to a certain extent and the adsorption capacity of these four gases on the transition metal atom-modified SnS2 monolayer has obviously improved. Moreover, the recovery time of Ag-SnS2/SOF2, Ag-SnS2/SO2F2, Au-SnS2/SOF2, Au-SnS2/SO2F2, and Pt-SnS2/SO2F2 is too short, indicating that these conditions have poor adsorption capacity and sensitivity to SF6 decomposition gases and are not suitable as detection materials for these gases. According to the different changes in conductivity during adsorption, it provides a feasible solution to detect each SF6 decomposition gas. This theoretical study effectively explained the adsorption and sensing properties between the metal-modified monolayers and gases.

TGF-ß-activated circRYK drives glioblastoma progression by increasing VLDLR mRNA expression and stability in a ceRNA- and RBP-dependent manner.

BACKGROUND: The TGF-ß signalling pathway is intricately associated with the progression of glioblastoma (GBM). The objective of this study was to examine the role of circRNAs in the TGF-ß signalling pathway. METHODS: In our research, we used transcriptome analysis to search for circRNAs that were activated by TGF-ß. After confirming the expression pattern of the selected circRYK, we carried out in vitro and in vivo cell function assays. The underlying mechanisms were analysed via RNA pull-down, luciferase reporter, and RNA immunoprecipitation assays. RESULTS: CircRYK expression was markedly elevated in GBM, and this phenotype was strongly associated with a poor prognosis. Functionally, circRYK promotes epithelial-mesenchymal transition and GSC maintenance in GBM. Mechanistically, circRYK sponges miR-330-5p and promotes the expression of the oncogene VLDLR. In addition, circRYK could enhance the stability of VLDLR mRNA via the RNA-binding protein HuR. CONCLUSION: Our findings show that TGF-ß promotes epithelial-mesenchymal transition and GSC maintenance in GBM through the circRYK-VLDLR axis, which may provide a new therapeutic target for the treatment of GBM.

IFITM3 inhibits severe fever with thrombocytopenia syndrome virus entry and interacts with viral Gc protein.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.

Erdr1 Drives Macrophage Programming via Dynamic Interplay with YAP1 and Mid1.

Erythroid differentiation regulator 1 (Erdr1) is a stress-induced, widely expressed, highly conserved secreted factor found in both humans and mice. Erdr1 is linked with the Hippo-YAP1 signaling. Initially identified as an inducer of hemoglobin synthesis, Erdr1 emerged as a multifunctional protein, especially in immune cells. Although Erdr1 has been implicated in regulating T cells and NK cell function, its role in macrophage remains unclear. This study explored the function and mechanism of Erdr1 in macrophage inflammatory response. The data demonstrated that Erdr1 could promote anti-inflammatory cytokine production, a function that also has been reported by previous research. However, I found Erdr1 also could play a proinflammatory role. The function of Erdr1 in macrophages depends on its dose and cell density. I observed that Erdr1 expression was inhibited in M1 macrophages but was upregulated in M2 macrophages compared with unpolarized macrophages. I hypothesized that Erdr1 balances the inflammatory response by binding with distinct adaptors dependent on varying concentrations. Mechanistically, I demonstrated YAP1 and Mid1 as the two adaptor proteins of Erdr1. The Erdr1-YAP1 interaction promotes anti-inflammatory cytokine production when Erdr1 levels are elevated, whereas the Erdr1-Mid1 interaction induces proinflammatory cytokine production when Erdr1 levels are decreased. This study highlights the effects of Erdr1 on regulating cytokine production from polarized macrophages potentially by regulating YAP1 in the nonclassical Hippo pathway.

Sensitive Materials Used in Surface Acoustic Wave Gas Sensors for Detecting Sulfur-Containing Compounds.

There have been many studies on surface acoustic wave (SAW) sensors for detecting sulfur-containing toxic or harmful gases. This paper aims to give an overview of the current state of polymer films used in SAW sensors for detecting deleterious gases. By covering most of the important polymer materials, the structures and types of polymers are summarized, and a variety of devices with different frequencies, such as delay lines and array sensors for detecting mustard gas, hydrogen sulfide, and sulfur dioxide, are introduced. The preparation method of polymer films, the sensitivity of the SAW gas sensor, the limit of detection, the influence of temperature and humidity, and the anti-interference ability are discussed in detail. The advantages and disadvantages of the films are analyzed, and the potential application of polymer films in the future is also forecasted.

CeO2 and Glucose Oxidase Co-Enriched Ti3C2Tx MXene for Hyperthermia-Augmented Nanocatalytic Cancer Therapy.

Foreseen as foundational in forthcoming oncology interventions are multimodal therapeutic systems. Nevertheless, the tumor microenvironment (TME), marked by heightened glucose levels, hypoxia, and scant concentrations of endogenous hydrogen peroxide could potentially impair their effectiveness. In this research, two-dimensional (2D) Ti3C2 MXene nanosheets are engineered with CeO2 nanozymes and glucose oxidase (GOD), optimizing them for TME, specifically targeting cancer therapy. Following our therapeutic design, CeO2 nanozymes, embodying both peroxidase-like and catalase-like characteristics, enable transformation of H2O2 into hydroxyl radicals for catalytic therapy while also producing oxygen to mitigate hypoxia. Concurrently, GOD metabolizes glucose, thereby augmenting H2O2 levels and disrupting the intracellular energy supply. When subjected to a near-infrared laser, 2D Ti3C2 MXene accomplishes photothermal therapy (PTT) and photodynamic therapy (PDT), additionally amplifying cascade catalytic treatment via thermal enhancement. Empirical evidence demonstrates robust tumor suppression both in vitro and in vivo by the CeO2/Ti3C2-PEG-GOD nanocomposite. Consequently, this integrated approach, which combines PTT/PDT and enzymatic catalysis, could offer a valuable blueprint for the development of advanced oncology therapies.

PTX3 activates POSTN and promotes the progression of glioblastoma via the MAPK/ERK signalling axis.

BACKGROUND: Intrinsic brain tumours such as glioblastoma (GBM) are believed to develop from neuroglial stem or progenitor cells. GBM accounts for approximately half of gliomas. GBM has a poor prognosis and a low 5-year survival rate. Pentraxin 3 (PTX3) is overexpressed in GBM, but the potential mechanism is unclear. METHODS: Glioblastoma data from the TCGA and CGGA databases were used to analyse PTX3 expression. Subsequently, in vivo and in vitro experiments were conducted to verify the effect of PTX3 silencing in glioma cells on EMT like process and GSC maintenance. The JASPAR database was used to predict the downstream genes of PTX3. POSTN is a novel target gene of PTX3 in gliomas, and this finding was validated using a luciferase reporter gene assay. Western blotting and KEGG enrichment analysis were used to predict the downstream pathway of POSTN, and it was found that the MAPK/ERK pathway might be related to the function of POSTN. RESULTS: GBM tissues have higher levels of PTX3 expression than normal brain tissues (NBTs). In functional tests, PTX3 promoted the EMT like process of GBM cells while maintaining the stem cell characteristics of GBM stem cells and enhancing their self-renewal. Moreover, we performed a dual luciferase reporter experiment to confirm that PTX3 binds to the POSTN promoter region. In addition, the expression of key proteins in the MAPK/ERK signalling pathway was increased after PTX3 overexpression. CONCLUSION: POSTN is a direct target of PTX3 that promotes GBM growth via the MAPK/ERK signalling pathway.

Gastrointestinal Surgery and Risk of Parkinson's Disease: A Meta-Analysis.

Several studies have explored gastrointestinal surgery and the risk of Parkinson's disease (PD), but the results of these studies are still controversial. This meta-analysis aimed to evaluate undergoing gastrointestinal surgery and the risk of PD in patients. PubMed, EMbase, the Cochrane Library, CNKI, and WanFang Data databases were electronically searched to collect studies from inception to 1 March 2023. Stata15.1 software was used to perform meta-analysis of the data. Of 260 references screened, 8 studies involving 9,596,121 people were included eventually. Gastrointestinal surgery had no significant effect on the risk of PD (OR = 1.059, 95% CI: 0.915-1.224, I2 = 90.4%, p = 0.443). Several subgroup analyses showed that the patients with different regions, different surgical locations and different sample sizes after gastrointestinal surgery were not associated with the risk of PD. Furthermore, sensitivity analysis confirmed that the patients after gastrointestinal surgery were not associated with the risk of PD. There was no significant effect of gastrointestinal surgery on the risk of PD, but more studies should be included to confirm this observation. Key Words: Gastrointestinal surgery, Risk factor, Parkinson's disease, Meta-analysis.