Real-Time Monitoring of CAR-T Cell Efficiency through a Biorthogonal Cycloaddition Labeling Strategy.

Chimeric antigen receptors (CARs) recognizing tumor-associated antigens (TAAs) effectively target tumor cells without using the major histocompatibility complex (MHC). However, CARs have inaccurate dose determination in clinical practice, and the methods that can solve this problem often produce cytotoxic substances, such as green fluorescent protein (GFP) insertion. Therefore, in this study, we tried to anchor harmless fluorescent labels on CAR-T cell membranes using highly biologically compatible strain-promoted alkyne-azide cycloaddition (SPAAC) without any byproducts. Our conjugated fluorescent label was stable on the CAR-T cell surface for at least two weeks, with excellent light stability and metrology. Also, this method enabled the rapid quantification of the living CAR-T cells without affecting their activity. Thus, this method is a promising reliable strategy for accurately diagnosing and treating cancer.

Study on the expression of c-Met in gastric cancer and its correlation with preoperative serum tumor markers and prognosis.

BACKGROUND: Studies have found that c-Met plays a critical role in the progression of solid tumors. This study aimed to investigate the expression of c-Met in gastric cancer (GC) and its correlation with preoperative serum tumor markers and prognosis, in order to provide a more theoretical basis for targeting c-Met in the treatment of GC. METHODS: Ninety-seven patients who underwent curative gastrectomy in our hospital from December 2013 to September 2015 were included in this study. The tissue microarray was constructed by paraffin-embedded tumor tissue of enrolled patients, including 97 GC points and 83 paracancerous points. Then, it was used for c-Met immunohistochemical staining, followed by an immunological H-score. The clinical baseline data and 5-year survival of patients with low and high c-Met expression were compared. Besides, the correlation between the expression of c-Met in tumor tissues and preoperative serum tumor markers was investigated. Finally, multivariate Cox regression analysis was used to explore the survival risk factors of patients. RESULTS: c-Met has a high expression rate in GC tissues 64.95% (63/97). The expression of c-Met was significantly different in different clinicopathological stages (p < 0.05); the high expression group also had a higher M stage and clinicopathological stage of GC. The correlation test between the c-Met H-score and CA125 was statistically significant (p = 0.004), indicating a positive correlation. Furthermore, high c-Met expression correlated with poor overall survival (OS) for 5 years (p = 0.005). It was also found that the high expression of c-Met in stage I-II patients was correlative with poor OS for 5 years (p = 0.026), while stage III-IV patients had no statistical significance (p > 0.05). Multivariate Cox regression analysis showed that c-Met might be an independent risk factor for survival 5 years after surgery. CONCLUSION: This study found that the high expression of c-Met in GC tissues was associated with poor 5-year OS in GC patients and was an independent risk factor for 5-year survival after curative gastrectomy. The expression of c-Met in GC tissues was also positively correlated with preoperative serum CA125.

Pivotal roles of nanoscale zerovalent iron supported on metal-organic framework material in cadmium (II) migration and transformation in soil.

Cadmium (Cd) contamination in soils is of great concern, and therefore the development of effective remediation technologies for cadmium contamination is urgent. In our study, nano zero-valent iron (NZVI) supported by metal-organic framework (MOF) materials (MOF-NZVI) were prepared using NaBH4 and FeCl3 to try to solve the soil Cd remediation problem. Herein, the effects and the mechanism of MOF-NZVI for the immobilization of Cd in contaminated soil was investigated. The results showed that MOF-NZVI was capable of converting Cd in soil from weak acid extractable and reducible fractions to oxidizable and residual states, thus effectively reducing the toxicity of Cd in soil. FTIR and XRD analysis confirmed that the dominant reaction mechanism between MOF-NVZI and Cd is adsorption with complexation, and the stabilization of Cd is achieved by the formation of compounds such as FeOCdOH.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures.

PURPOSE: To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture. METHODS: A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score. RESULTS: There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment. CONCLUSION: In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

Robotic bariatric surgery for the obesity: a systematic review and meta-analysis.

OBJECTIVE: The aim of this meta-analysis is to evaluate the safety and efficacy of bariatric surgery (BS) in patients with obesity by robotic bariatric surgery (RBS) compared with laparoscopic bariatric surgery (LBS). METHODS: The study was performed through searching in Pubmed, Web of Science, Embase database and Cochrane Library until March 31, 2020 comparing RBS with LBS. Data were calculated on the following endpoints: operative time, length of hospital stay, reoperation within 30 days, overall complications, leak, stricture, pulmonary embolisms, estimated blood loss and mortality. Data as relative risks (OR), or weighted mean difference (WMD) were summarized with 95% confidence interval (CI). Risk of publication bias was assessed through standard methods. RESULTS: Thirty eligible trials including 7,239 robotic and 203,181 laparoscopic surgery cases showed that RBS was referred to attain longer operative time [WMD = 27.61 min; 95%CI (16.27-38.96); P < 0.01] and lower mortality [OR 2.40; 95% CI (1.24-4.64); P = 0.009] than LBS. Length of hospital stay [WMD = - 0.02; 95% CI (- 0.19-0.15); P = 0.819], reoperation within 30 days [OR 1.36; 95% CI (0.65-2.82); P = 0.411], overall complications [OR 0.88; 95% CI (0.68-1.15); P = 0.362], leak [OR 1.04; 95% CI (0.43-2.51); P = 0.933], stricture [OR 1.05; 95% CI (0.52-2.12); P = 0.895], pulmonary embolisms [OR 1.97; 95% CI (0.93-4.17); P = 0.075], estimated blood loss[WMD = - 1.93; 95% CI (- 4.61-0.75); P = 0.158] were almost similar in both RBS group and LBS group. Three was no statistically significant difference between RRYGB and LRYGB in EWL%, no statistical significance between RSG and LSG after 1 year, 2 years and 3 years. CONCLUSION: RBS presented lower mortality within 90 days and longer operative time in this meta-analysis with similar safety and efficacy for the obesity compared with LBS in other outcomes. Additionally, RBS might be beneficial in the future if it would be evaluated in comprehensive and long-term endpoints.

Involute the reactivity of persulfate with zero-valent iron for enhanced removal of arsenic (V) in aspect involvement of Fe2+ or Fe3.

Being a fundamental issue regarding sewage treatment, heavy metals removal from industrial effluents has been subject to intense scrutiny in both the academic and practical worlds. The removal of pentavalent arsenic (As(V)), one of the most poisonous pollutants, was investigated using a sodium persulfate and iron powder system activated by ferrous ions (Fe2+-ZVI-PS). As(V) could be effectively removed by an Fe2+-ZVI-PS system in a timely fashion (minute scale) with high removal rates (more than 90.0%) over a wide range of pH (1-9) and concentration (20-100 mg/L). The removal of As(V) by the Fe2+-ZVI-PS system integrated favorably with the pseudo-second-order reaction kinetics. Researches on X-ray photoelectron spectroscopy (XPS) demonstrated that the Fe2+-ZVI-PS system enables the removal of As(V) through the process of co-precipitation and adsorption. Our findings thus emphasized that the Fe2+-ZVI-PS system should be an effective trigger to purifying arsenic from the environment. Our results indicated that the Fe2+-ZVI-PS system could be an effective candidate for remediation of arsenic in the environment.

The meta-learning method for the ensemble model based on situational meta-task.

Introduction: The meta-learning methods have been widely used to solve the problem of few-shot learning. Generally, meta-learners are trained on a variety of tasks and then generalized to novel tasks. Methods: However, existing meta-learning methods do not consider the relationship between meta-tasks and novel tasks during the meta-training period, so that initial models of the meta-learner provide less useful meta-knowledge for the novel tasks. This leads to a weak generalization ability on novel tasks. Meanwhile, different initial models contain different meta-knowledge, which leads to certain differences in the learning effect of novel tasks during the meta-testing period. Therefore, this article puts forward a meta-optimization method based on situational meta-task construction and cooperation of multiple initial models. First, during the meta-training period, a method of constructing situational meta-task is proposed, and the selected candidate task sets provide more effective meta-knowledge for novel tasks. Then, during the meta-testing period, an ensemble model method based on meta-optimization is proposed to minimize the loss of inter-model cooperation in prediction, so that multiple models cooperation can realize the learning of novel tasks. Results: The above-mentioned methods are applied to popular few-shot character datasets and image recognition datasets. Furthermore, the experiment results indicate that the proposed method achieves good effects in few-shot classification tasks. Discussion: In future work, we will extend our methods to provide more generalized and useful meta-knowledge to the model during the meta-training period when the novel few-shot tasks are completely invisible.

Notable conservation gaps for biodiversity, ecosystem services and climate change adaptation on the Tibetan Plateau, China.

Incorporating biodiversity, ecosystem services (ESs) and climate change adaptation into the conservation targets of protected areas (PAs) is being acknowledged. Targeting conservation actions requires a thorough understanding of the relationship between PAs and these important regions. However, few studies have identified conservation gaps while simultaneously considering these three aspects. Here, we assessed the representativeness of the PAs network for biodiversity, ESs and climate refugia (as a proxy for climate change adaptation ability) on the Tibetan Plateau (TP). Our analysis showed that these priority conservation regions were primarily located in the south and southeast of the TP, while they were impacted by intense human pressure. Most ESs and all types of species richness showed a significant positive correlation. Additionally, a positive correlation between multiple climate refugia and different types of species richness was detected. Representativeness analysis revealed notable conservation gaps for these three aspects in existing PAs, highlighting the urgency of adjusting their distribution and improving their representativeness. By integrating these conservation targets, priority regions for future conservation were further delineated. Taken together, our findings contribute to improving the efficiency of PAs and optimizing conservation planning.

Application of targeted diagnosis of PSMA in the modality shift of prostate cancer diagnosis: a review.

Prostate cancer (PCa) is a serious threat to the health of men all over the world. The progression of PCa varies greatly among different individuals. In clinical practice, some patients often progress to advanced PCa. Therefore, accurate imaging for diagnosis and staging of PCa is particularly important for clinical management of patients. Conventional imaging examinations such as MRI and CT cannot accurately diagnose the pathological stages of advanced PCa, especially metastatic lymph node (LN) stages. As a result, developing an accurate molecular targeted diagnosis is crucial for advanced PCa. Prostate specific membrane antigen (PSMA) is of great value in the diagnosis of PCa because of its specific expression in PCa. At present, researchers have developed positron emission tomography (PET) targeting PSMA. A large number of studies have confirmed that it not only has a higher tumor detection rate, but also has a higher diagnostic efficacy in the pathological stage of advanced PCa compared with traditional imaging methods. This review summarizes recent studies on PSMA targeted PET in PCa diagnosis, analyzes its value in PCa diagnosis in detail, and provides new ideas for urological clinicians in PCa diagnosis and clinical management.

Construction of targeted 10B delivery agents and their uptake in gastric and pancreatic cancer cells.

Boron Neutron Capture Therapy (BNCT) is a new binary radiation therapy for tumor tissue, which kills tumor cells with neutron capture reaction. Boron neutron capture therapy has become a technical means for glioma, melanoma, and other diseases has been included in the clinical backup program. However, BNCT is faced with the key problem of developing and innovating more efficient boron delivery agents to solve the targeting and selectivity. We constructed a tyrosine kinase inhibitor-L-p-boronophenylalanine (TKI-BPA) molecule, aiming to improve the selectivity of boron delivery agents by conjugating targeted drugs while increasing the molecular solubility by adding hydrophilic groups. It shows excellent selectivity in differential uptake of cells, and its solubility is more than 6 times higher than BPA, leading to the saving of boron delivery agents. This modification method is effective for improving the efficiency of the boron delivery agent and is expected to become a potential alternative with high clinical application value.

Supramolecular Nanozyme System Based on Polydopamine and Polyoxometalate for Photothermal-Enhanced Multienzyme Cascade Catalytic Tumor Therapy.

The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using ß-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (•OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.

Application and optimization of prostate-specific antigen screening strategy in the diagnosis of prostate cancer: a systematic review.

Currently, prostate cancer (PCa) poses a global risk to the well-being of males. Over the past few years, the utilization of prostate-specific antigen (PSA) screening has become prevalent in the identification and management of PCa, which has promoted a large number of patients with advanced PCa to receive timely treatment and reduce the mortality. Nevertheless, the utilization of PSA in PCa screening has sparked debate, and certain research has validated the potential for overdiagnosis and overtreatment associated with PSA screening. Hence, in order to decrease the mortality rate of PCa patients and prevent unnecessary diagnosis and treatment, it is crucial to carefully choose the suitable population and strategy for PSA screening in PCa. In this systematic review, the clinical studies on PSA screening for the diagnosis and treatment of PCa were thoroughly examined. The review also delved into the effects and mechanisms of PSA screening on the prognosis of PCa patients, examined the factors contributing to overdiagnosis and overtreatment, and put forth strategies for optimization. The objective of this research is to offer valuable recommendations regarding the utilization of PSA screening for the detection and management of PCa.

Boron Neutron Capture Therapy: Current Status and Challenges.

Boron neutron capture therapy (BNCT) is a re-emerging therapy with the ability to selectively kill tumor cells. After the boron delivery agents enter the tumor tissue and enrich the tumor cells, the thermal neutrons trigger the fission of the boron atoms, leading to the release of boron atoms and then leading to the release of the α particles (4He) and recoil lithium particles (7Li), along with the production of large amounts of energy in the narrow region. With the advantages of targeted therapy and low toxicity, BNCT has become a unique method in the field of radiotherapy. Since the beginning of the last century, BNCT has been emerging worldwide and gradually developed into a technology for the treatment of glioblastoma multiforme, head and neck cancer, malignant melanoma, and other cancers. At present, how to develop and innovate more efficient boron delivery agents and establish a more accurate boron-dose measurement system have become the problem faced by the development of BNCT. We discuss the use of boron delivery agents over the past several decades and the corresponding clinical trials and preclinical outcomes. Furthermore, the discussion brings recommendations on the future of boron delivery agents and this therapy.

The Influence of the Development of the Internet of Things Industry on the Optimization of the High- and New-Tech Industry Structure under the Wireless Mobile Network.

At present, the pressure on China's economic development is increasing day by day due to the profound changes in the internal and external environment. The global economic pattern is undergoing significant changes in terms of the external environment. Adjusting and optimizing the industrial structure will aid in achieving the goal of facilitating transformation through steady growth in the short term. Meanwhile, it will also accelerate sustainable economic development. In this study, the relevant theories of industrial structure optimization are described based on the impact of wireless mobile networks and the Internet of things (IoT) industry. Based on the gray correlation degree, the high- and new-tech industries under the development of the IoT industry are analyzed and the impact of optimization of the high- and new-tech industry structure is investigated. The results show that the development of the IoT industry has driven the development of the high- and new-tech industry. The gray correlation between the development of the IoT industry and the high- and new-tech industry obtained is 0.64, indicating a strong correlation. The average output share of the electronic computer and office equipment manufacturing industries is 47.09%. The average output ratio of the industrial structure optimization of the electronics and communication manufacturing industry is 42.55%. Moreover, the proportion of the output of medical manufacturing and medical equipment and instrument manufacturing industrial structure optimization is small, 15.63% and 10.54%, respectively. The results have significant value in the research on the impact of the development of the IoT industry on the high- and new-tech industry under the wireless mobile network and the effect of its industrial structure optimization.

A Bibliometric and Knowledge-Map Analysis of CAR-T Cells From 2009 to 2021.

Objectives: A bibliometric and knowledge-map analysis is used to explore hotspots' evolution and development trends in the CAR-T cell field. By looking for research hotspots and new topics, we can provide new clues and ideas for researchers in this field. Methods: The articles and reviews regarding CAR-T cells were retrieved and obtained from the Web of Science Core Collection (WOSCC) on October 28th, 2021. CtieSpace [version 5.8.R3 (64-bit)] and VOSviewer (version 1.6.17) were used to conduct the bibliometric and knowledge-map analysis. Results: 660 authors from 488 institutions in 104 countries/regions published 6,867 papers in 1,212 academic journals. The United States was absolutely in the leading position in this research field. The institution that contributed the most publications was the University of Pennsylvania. Carl H June published the most articles, while Shannon L Maude had the most co-citations. However, there was little cooperation between countries. After 2012, cooperation among various institutions was also small. The journals that published the most CAR-T cell-related papers were Frontiers in immunology and Cancers. Nevertheless, Blood and The New England Journal of Medicine were the most commonly co-cited journals. The most influential research hotspots were the research of CAR-T cells in hematological malignancies, the related research of cytokine release syndrome (CRS), CD19, and the anti-tumor activity and efficacy of CAR-T cells. The latest hotspots and topics included the study of CAR-T cells in solid tumors, universal CAR-T cells, CAR-NK cells, CD22, and anakinra (the IL-1 receptor antagonist). The research of CAR-T cells in solid tumors was a rapidly developing hot field. Emerging topics in this field mainly included the study of CAR-T cells in glioblastoma (related targets: IL13Rα2, EGFRvIII, and HER2), neuroblastoma (related target: GD2), sarcoma (related target: HER2), and pancreatic cancer (related target: mesothelin), especially glioblastoma. Conclusion: As an anti-tumor therapy with great potential and clinical application prospects, CAR-T cell therapy is still in a stage of rapid development. The related field of CAR-T cells will remain a research hotspot in the future.

Development of tannin-bridged cerium oxide microcubes-chitosan cryogel as a multifunctional wound dressing.

Efficient resolution of oxidative stress, inflammation, and bacterial infections is crucial for wound healing. To surmount these problems, tannic acid (TA)-bridged CeO2 microcubes and chitosan (CS) (CS-TA@CeO2) cryogel was fabricated through hydrogen bonding interactions as a multifunctional wound dressing. Successful introduction and uniform incorporation TA@CeO2 microtubules enter the CS network. Thus-obtained CS-TA@CeO2 cryogels displayed a suitable porous structure and swelling rate. Cryogels has excellent tissue adhesion, blood cell coagulation and hemostasis, anti-infection, and cell recruitment functions. In addition, the cryogel also showed good antibacterial activity against gram-positive bacteria and gram-negative bacteria. Based on the in vivo study of the multifunctional mixed cryogels, it promotes fibroblasts' adhesion and proliferation and significantly improves cell proliferation and tissue remodelling in wound beds. Furthermore, the chronic wound healing process in infected full-thickness skin defect models showed that cryogels significantly enhanced angiogenesis, collagen deposition and granulation tissue formation by providing a large amount of antioxidant activity. Therefore, this multifunctional mixed cryogels has potential clinical application value.

Special Chimeric Antigen Receptor (CAR) Modifications of T Cells: A Review.

Chimeric antigen receptor (CAR) -T cell therapy has become one of the hot topics in tumor immunity research in recent years. Although CAR-T cell therapy is highly effective in treating hematological malignancies, there are numerous obstacles that prevent CAR-T cells from having anti-tumor effects. Traditional CARs, from the first to the fourth generation, are incapable of completely overcoming these challenges. Therefore, identifying ways to boost the efficacy of CAR-T cells by utilizing the limited tumor surface antigens has become an urgent area of research. Certain special CARs that have special structures, special systems, or are greatly improved on the basis of traditional CARs, such as tandem CAR, dual-signaling CARs, AND-gate CARs, inhibitory CAR, AND-NOT CARs, CARs with three scFvs, ON/OFF-switch CARs, and universal CARs have been introduced. This study aims to use these special CARs to improve the anti-tumor ability, accuracy, and safety of CAR-T cells. In addition to summarizing various special CARs of T cells, this paper also expounds some of our own conjectures, aiming to provide reference and inspiration for CARs researchers.

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future.

In recent years, with the breakthrough of CAR-T cells in the treatment of hematological tumors, they are increasingly being used to treat solid tumors, including urologic neoplasms. There are many relatively specific targets for urologic neoplasms, especially prostate cancer. Besides, urologic neoplasms tend to progress more slowly than tumors in other organs of the body, providing ample time for CAR-T cell application. Therefore, CAR-T cells technology has inherent advantages in urologic neoplasms. CAR-T cells in the treatment of urologic neoplasms have been extensively studied and preliminary achievements have been made. However, no breakthrough has been made due to the problems of targeting extra-tumor cytotoxicity and poor anti-tumor activity. we systematacially summarized the research actuality of CAR-T cells in urologic neoplasms, discussed the potential value and difficulties of the research. The application of CAR-T cells in the treatment of urologic neoplasms requires improvement of function through screening for better targets, modification of CAR structures, or in combination with other antitumor approaches.

Identification of differentially expressed miRNAs derived from serum exosomes associated with gastric cancer by microarray analysis.

AIMS: To explore the differentially expressed microRNAs (DEMs) in serum exosomes between gastric cancer (GC) patients and healthy people to provide new targets for GC diagnosis and treatment. METHODS: DEMs in serum exosomes were screened by microarray analysis and verified by RT-qPCR. The target genes of DEMs were predicted using Targetscan and miRTarBase databases and then overlapped with the DEGs of STAD in TCGA database to obtain the common target genes. Biological function and pathway enrichment were analyzed using enrichr database, and a PPI network was constructed using STRING database. The potential target genes of DEMs were identified using the MCODE and cytoHubba plug-ins of Cytoscape software. Survival analysis were conducted using KMP and TCGA databases. The DEMs -target genes-pathways network was established using Cytoscape software. A Cox proportional hazards regression model formed by optimal target genes was used to access the reliability of this prediction process. RESULTS: Three serum exosomal microRNAs (exo-miRNAs, has-miR-1273 g-3p, has-miR-4793-3p, has-miR-619-5p) were identified to be highly expressed in GC patients and performed excellent diagnostic ability. A total of 179 common target genes related to GC were predicted. They were mainly involved in 79 GO functional annotations and 6 KEGG pathways. The prognostic model formed by eight optimal target genes (TIMELESS, DNA2, MELK, CHAF1B, DBF4, PAICS, CHEK1 and NCAPG2), which were low-risk genes of GC, also performed perfect prognostic ability. CONCLUSIONS: Serum exosomal has-miR-1273 g-3p, has-miR-4793-3p and has-miR-619-5p can be used as new diagnostic biomarkers for GC. Among them, serum exosomal hsa-miR-1273 g-3p / hsa-miR-4793-3p targets MELK and hsa-miR-619-5p targets NCAPG2 were identified as novel mechanisms involved in the development of GC. It provides new targets for the diagnosis and treatment of GC by exo-miRNAs.

Opportunities and challenges of targeting c-Met in the treatment of digestive tumors.

At present, a large number of studies have demonstrated that c-Met generally exerts a crucial function of promoting tumor cells proliferation and differentiation in digestive system tumors. c-Met also mediates tumor progression and drug resistance by signaling interactions with other oncogenic molecules and then activating downstream pathways. Therefore, c-Met is a promising target for the treatment of digestive system tumors. Many anti-tumor therapies targeting c-Met (tyrosine kinase inhibitors, monoclonal antibodies, and adoptive immunotherapy) have been developed in treating digestive system tumors. Some drugs have been successfully applied to clinic, but most of them are defective due to their efficacy and complications. In order to promote the clinical application of targeting c-Met drugs in digestive system tumors, it is necessary to further explore the mechanism of c-Met action in digestive system tumors and optimize the anti-tumor treatment of targeting c-Met drugs. Through reading a large number of literatures, the author systematically reviewed the biological functions and molecular mechanisms of c-Met associated with tumor and summarized the current status of targeting c-Met in the treatment of digestive system tumors so as to provide new ideas for the treatment of digestive system tumors.