BACKGROUND:Tumor microenvironment can participate in the occurrence and development of gastric cancer and promote chemotherapy resistance in various ways.Among them,the tumor microenvironment crosstalk mediated by exosomal miRNAs can induce matrix reprogramming,participate in tumor heterogeneity,and form a microenvironment conducive to tumor proliferation,migration,invasion,immune escape,and chemotherapy resistance.OBJECTIVE:To review the mechanism of action of exosomal miRNAs in the microenvironment of gastric cancer and its application in the diagnosis and prognosis assessment of gastric cancer in recent years.METHODS:"Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker"for English search terms and"exosomal miRNAs,gastric cancer"for Chinese search terms were searched in PubMed and CNKI databases.The search period was from 2017 to 2024.After preliminary screening by reading the title and abstract,the articles with poor correlation and repeated content were excluded,and 77 articles were finally included for induction and discussion.RESULTS AND CONCLUSION:(1)Exosomes,as important carriers of intercellular information exchange,can carry a variety of information substances such as miRNA,and realize intercellular signal transmission through three ways:activation of cell surface receptors on target cells,fusion with the plasma membrane of recipient cells,and endocytosis.(2)Exosomal miRNAs play an important role in the progression of gastric cancer by regulating the proliferation,apoptosis,autophagy,angiogenesis,invasion and metastasis,immune response,and the formation of drug resistance of gastric cancer cells.(3)The interaction between miRNAs and target mRNA and its regulatory network are widely found in tumorigenesis and human cancer development.Different types of exosomal miRNAs have different effects on the regulation of apoptosis of gastric cancer cells,and the effects of different exosomal miRNAs on apoptosis related proteins and pathways of gastric cancer cells are screened.Rational use of its inducers or inhibitors can regulate the apoptosis level of gastric cancer cells.(4)Exosomal miRNAs of different cell origin play an important role in the establishment of tumor microenvironment,angiogenesis,immune response,and chemotherapy resistance by inducing M1-polarized macrophages to M2 type.(5)Exosomal miRNAs exist extensively and stably in blood and other body fluids,and their differential expression in patients with gastric cancer can be used as a basis for diagnosis,prognosis,and treatment of patients with gastric cancer.Currently,exosomal miRNAs widely studied as biomarkers include miR-379-5p,miR-590-5p,miR-29s,miR-21,etc.Among them,the sensitivity and specificity of miR-590-5p are 63.7％and 86％,respectively.The expression level of miR-590-5p is closely related to the overall survival rate and the depth of invasion of gastric cancer patients.(6)The design of exosomal miRNAs mimics or inhibitors and their targeted delivery to the tumor site using nano-delivery vectors(such as exosomes and liposomes)to restore the normal level of miRNAs may be a new strategy for the treatment of gastric cancer.(7)Although exosomal miRNAs have great application prospects in the diagnosis and treatment of gastric cancer patients,there are still some problems to be solved.For example,the potential targets and mechanisms of exosomal miRNAs have not been fully explored,and their effectiveness and safety need to be further confirmed.The extraction and purification of exosomes lack standardized large-scale preparation processes.

BACKGROUND:At present,chemotherapeutic drugs are mainly used for the treatment of tumors,but there are problems such as drug resistance and adverse reactions.The exosome drug delivery system not only avoids the toxicity of synthetic nanoparticles,but also increases the bioavailability and biocompatibility of the drugs.It can be modified by biological,physical,and chemical methods to form a new type of nano-drug delivery platform.OBJECTIVE:To review the construction strategy of exosome drug delivery system,the application status of exosome drug delivery system in tumor diseases and the current challenges.METHODS:PubMed and CNKI were searched with"exosomal,tumor,microvesicle,extracellular vesicles,engineered,therapeutics,characterization,isolation,drug delivery,targeting,modification strategies,physics,chemistry,biology"as English search terms and"exosomes,drug delivery,tumor"as Chinese search terms.A total of 132 articles were included for in-depth induction and discussion.RESULTS AND CONCLUSION:(1)The technical methods of exosome extraction,including ultracentrifugation,filtration,and kit extraction,can efficiently isolate exosomes,but the process is complicated and time-consuming,and large-scale extraction of exosomes cannot be achieved.(2)Engineered exosomes can be divided into four categories:gene editing engineering,which improves function through genetic modification;endogenous engineering,using inflammatory factors and other pretreatment to enhance drug delivery;exogenously engineered to encapsulate drugs directly in exosomes;hybrid engineering,combining exosomes with lipid nanoparticles to form new particles.Some have entered clinical trials for cancer treatment,but most are at an early stage.In contrast,genetically engineered exosomes are considered as an important direction for future drug delivery due to their high targeting and customization potential.(3)There are still many limitations to realize the clinical transformation of engineered exosomes.At the technical level,large-scale production,purification,and drug loading efficiency are urgent to be solved.In production,high cost and batch stability affect its popularity.In terms of safety,immunogenicity and potential toxicity need to be comprehensively evaluated.Furthermore,the imperfect regulatory policies and the complexity of the approval process also constitute obstacles to its clinical translation.(4)In the future,it is necessary to promote the clinical translation process through technical innovation,cost control,safety improvement,and policy improvement.

BACKGROUND:Tumor microenvironment can participate in the occurrence and development of gastric cancer and promote chemotherapy resistance in various ways.Among them,the tumor microenvironment crosstalk mediated by exosomal miRNAs can induce matrix reprogramming,participate in tumor heterogeneity,and form a microenvironment conducive to tumor proliferation,migration,invasion,immune escape,and chemotherapy resistance.OBJECTIVE:To review the mechanism of action of exosomal miRNAs in the microenvironment of gastric cancer and its application in the diagnosis and prognosis assessment of gastric cancer in recent years.METHODS:"Exosomal miRNAs,gastric cancer,angiogenesis,apoptosis,proliferation,migration,autophagy,invasion,immune response,chemotherapy resistance,biomarker"for English search terms and"exosomal miRNAs,gastric cancer"for Chinese search terms were searched in PubMed and CNKI databases.The search period was from 2017 to 2024.After preliminary screening by reading the title and abstract,the articles with poor correlation and repeated content were excluded,and 77 articles were finally included for induction and discussion.RESULTS AND CONCLUSION:(1)Exosomes,as important carriers of intercellular information exchange,can carry a variety of information substances such as miRNA,and realize intercellular signal transmission through three ways:activation of cell surface receptors on target cells,fusion with the plasma membrane of recipient cells,and endocytosis.(2)Exosomal miRNAs play an important role in the progression of gastric cancer by regulating the proliferation,apoptosis,autophagy,angiogenesis,invasion and metastasis,immune response,and the formation of drug resistance of gastric cancer cells.(3)The interaction between miRNAs and target mRNA and its regulatory network are widely found in tumorigenesis and human cancer development.Different types of exosomal miRNAs have different effects on the regulation of apoptosis of gastric cancer cells,and the effects of different exosomal miRNAs on apoptosis related proteins and pathways of gastric cancer cells are screened.Rational use of its inducers or inhibitors can regulate the apoptosis level of gastric cancer cells.(4)Exosomal miRNAs of different cell origin play an important role in the establishment of tumor microenvironment,angiogenesis,immune response,and chemotherapy resistance by inducing M1-polarized macrophages to M2 type.(5)Exosomal miRNAs exist extensively and stably in blood and other body fluids,and their differential expression in patients with gastric cancer can be used as a basis for diagnosis,prognosis,and treatment of patients with gastric cancer.Currently,exosomal miRNAs widely studied as biomarkers include miR-379-5p,miR-590-5p,miR-29s,miR-21,etc.Among them,the sensitivity and specificity of miR-590-5p are 63.7％and 86％,respectively.The expression level of miR-590-5p is closely related to the overall survival rate and the depth of invasion of gastric cancer patients.(6)The design of exosomal miRNAs mimics or inhibitors and their targeted delivery to the tumor site using nano-delivery vectors(such as exosomes and liposomes)to restore the normal level of miRNAs may be a new strategy for the treatment of gastric cancer.(7)Although exosomal miRNAs have great application prospects in the diagnosis and treatment of gastric cancer patients,there are still some problems to be solved.For example,the potential targets and mechanisms of exosomal miRNAs have not been fully explored,and their effectiveness and safety need to be further confirmed.The extraction and purification of exosomes lack standardized large-scale preparation processes.

BACKGROUND:At present,chemotherapeutic drugs are mainly used for the treatment of tumors,but there are problems such as drug resistance and adverse reactions.The exosome drug delivery system not only avoids the toxicity of synthetic nanoparticles,but also increases the bioavailability and biocompatibility of the drugs.It can be modified by biological,physical,and chemical methods to form a new type of nano-drug delivery platform.OBJECTIVE:To review the construction strategy of exosome drug delivery system,the application status of exosome drug delivery system in tumor diseases and the current challenges.METHODS:PubMed and CNKI were searched with"exosomal,tumor,microvesicle,extracellular vesicles,engineered,therapeutics,characterization,isolation,drug delivery,targeting,modification strategies,physics,chemistry,biology"as English search terms and"exosomes,drug delivery,tumor"as Chinese search terms.A total of 132 articles were included for in-depth induction and discussion.RESULTS AND CONCLUSION:(1)The technical methods of exosome extraction,including ultracentrifugation,filtration,and kit extraction,can efficiently isolate exosomes,but the process is complicated and time-consuming,and large-scale extraction of exosomes cannot be achieved.(2)Engineered exosomes can be divided into four categories:gene editing engineering,which improves function through genetic modification;endogenous engineering,using inflammatory factors and other pretreatment to enhance drug delivery;exogenously engineered to encapsulate drugs directly in exosomes;hybrid engineering,combining exosomes with lipid nanoparticles to form new particles.Some have entered clinical trials for cancer treatment,but most are at an early stage.In contrast,genetically engineered exosomes are considered as an important direction for future drug delivery due to their high targeting and customization potential.(3)There are still many limitations to realize the clinical transformation of engineered exosomes.At the technical level,large-scale production,purification,and drug loading efficiency are urgent to be solved.In production,high cost and batch stability affect its popularity.In terms of safety,immunogenicity and potential toxicity need to be comprehensively evaluated.Furthermore,the imperfect regulatory policies and the complexity of the approval process also constitute obstacles to its clinical translation.(4)In the future,it is necessary to promote the clinical translation process through technical innovation,cost control,safety improvement,and policy improvement.

Objective To compare WHO 2004 and WHO 1973 pathological grading methods of non-muscle invasive urothelial neoplasms. Methods The clinical pathological features of 160 non-muscle invasive urothelial neoplasms patients, treated in our hospital from February, 1998 to Decem-ber, 2008, were re-graded according to WHO 2004 and WHO 1973 classification system. To evaluate recurrence and progression of all the patients during the follow up period, we used statistical method to analyses the differences between two classification system. Results There were 160 patients, ac-cording to WHO 1973 classification methods: 5 cases of papilloma, 52 cases of grade 1 tumors, 83 ca-ses of grade 2 and 20 cases of grade 3;By WHO 2004 classification method: 7 cases of papilloma, 31 cases of low-grade malignant potential of urothelial papilloma, 99 cases of low-grade papillary urotheli-al carcinoma and 23 cases of high-grade papillary urothelial carcinoma. There was no difference in re-currence among the grades of WHO 2004 and WHO 1973 pathological grading system (both P>0.05). Regarding the progress of non-muscle invasive papillary urothelial neoplasms, no significant difference was found among grades of WHO 1973 classification system(P>0.05)while difference exis-ted among grades of WHO 2004 pathological grading system (P<0.05), especially between papillary neoplasm of low malignant potential (PNLMP) and high grade papillary urothelial carcinomas(HG-PUC) (P<0.01). Moreover, HGPUC grade had more progression rate (30.4%) than G_3 grade (15.0%). Conclusions Compare to G_3 grade, HGPUC grade was more easily to make progress in pa-tients,due to this grade include more high malignant papillary urothelial carcinomas. Therefore, it is necessary for urologists to use a more rigorously follow up and therapy method in connection with HG-PUC grade of new classification system.