Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

OBJECTIVE To explore the diagnostic value of combined detection of microRNA(miRNA)and alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)in ascites and serum ex-tracellular vesicles(EVs)for hepatitis B virus(HBV)-related primary hepatocellular carcinoma(HCC).METHODS From Nov.2023 to Nov.2024,41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chi-nese PLA General Hospital were selected as study subjects.Ascites and serum samples were collected.Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression levels of miR-21,miR-125a,miR-150 and miR-200a in EVs.Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites,serum and EVs from ascites and serum.An artificial neural network was utilized to con-struct a combined diagnostic model of serum and ascites markers.RESULTS The area under the curve(AUC)for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933.The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912.By screening all detected indicators using an artificial neural network and incorporating indicators with a relative im-portance＞0.5 into the diagnostic model,the model included four indicators:ascites AFP,ascites EVs miR-21,ascites EVs miR-200a and serum EVs miR-200a.This model had a sensitivity of 80.77％,a specificity of 87.80％and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.CONCLUSION The combined diagnos-tic markers of miRNA,AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

Objective To establish an expert consensus on the management of low anterior resection syndrome(LARS)in patients with rectal cancer post-surgery(hereinafter referred to as"consensus"),aiming to standardize the related work of medical institutions in the context of post-operative LARS.Methods A comprehensive search of domestic and international databases was conducted to collect guidelines,expert consensuses,systematic reviews,evidence summaries,and original research related to post-operative LARS in rectal cancer published from the establishment of the databases until August 2024.Based on clinical practice experience,a preliminary draft of the"consensus"was formed.From September to November 2024,22 experts were invited to participate in 2 rounds of expert consultations,during which the draft content was revised and improved,and the final version of the"consensus"was determined through expert validation.Results A total of 22 experts responded,achieving a response rate of 100％.The effective recovery rate of the consultation questionnaires in both rounds was 100％,with an expert authority coefficient of 0.89,a judgment coefficient of 0.97,and a familiarity degree of 0.84.The Kendall harmony coefficients for the 2 rounds of expert consultations were 0.122 and 0.136,respectively(P＜0.001).This consensus covers 5 main aspects:definition,assessment,prevention,treatment,and follow-up management of LARS.Conclusion This consensus demonstrates a high level of scientific rigor and can provide a strong reference for clinical nursing personnel in the specialized care of rectal cancer patients with post-operative LARS.

OBJECTIVE To mine the adverse drug events （ADE） signals for gilteritinib， and provide a reference for safe drug use in clinic. METHODS ADE reports with gilteritinib as the primary suspected drug were extracted from the FDA Adverse Event Reporting System （FAERS） database from February 1st， 2018 to December 31st， 2023. Reporting odds ratio （ROR） and proportional reporting ratio （PRR） were applied to detect the risk signals from the data in the FAERS database. The classification and statistics of collected signal data were conducted by using the preferred term （PT） and systemic organ class （SOC） in ADE terminology set of the Medical Dictionary for Regulatory Activities （24.1 edition）. RESULTS Totally， 2 755 gilteritinib-related ADE reports were collected from the database， involving 676 ADE signals （95 positive signals）， 313 PTs and 25 SOCs. Among them， nine signals were not recorded in the package insert. The top 5 PTs consisted of abnormal liver function， decreased platelet count， febrile neutropenia， pneumonia and myelosuppression. The top 6 SOCs for positive signal counts were examinations， general disorders and administration site conditions， respiratory， thoracic and mediastinal disorders， infections and infestations， heart organ disorders， and nervous system disorders. ADEs not recorded in the drug package insert included pneumonia， myelosuppression， decreased blood cell count， sepsis， hemorrhage， infection （not specifically referred to）， septic shock， respiratory failure， and aspergillosis. CONCLUSIONS In addition to paying attention to common ADEs such as liver dysfunction and thrombocytopenia， it is necessary to monitor ADEs with strong signals that are not mentioned in the drug instructions when using gefitinib， such as pneumonia， bone marrow suppression， cytopenia， sepsis， bleeding， infection （not specifically referred to）， septic shock， respiratory failure， Aspergillus infection， elevated serum creatinine and interstitial lung disease.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.

BACKGROUND: Osteoarthritis (OA), a degenerative joint disorder, is a major reason of disability in adults. Accumulating evidences have proved that bone marrow mesenchymal stem cells (BMSCs)-carried exosomes play a significant therapeutic effect on OA. However, the precise regulatory network remains unknown. METHODS: OA and normal cartilage samples were acquired from patients, and chondrocytes were exposed to IL-1b to conduct a cellular OA model. Exosomes prepared from BMSCs were identified using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Cell viability was determined with CCK-8 assay. Inflammatory injury was assessed by LDH and inflammatory factors (TNF-a and IL-6) using corresponding ELISA kits, respectively. Ferroptosis was evaluated by GSH, MDA and iron levels using corresponding kits, and ROS level with DCFH-DA. The expressions of genes/proteins were determined with RT-qPCR/western bolt. RNA immunoprecipitation and luciferase activity assay were conducted for testing the interactions of small nucleolar RNA host gene 7 (SNHG7)/ferroptosis suppressor protein 1 (FSP1) and miR-485-5p. RESULTS: The expressions of SNHG7 and FSP1 were both reduced in IL-1b-induced chondrocytes and OA cartilage tissues, and there was a positive correlation between them in clinical level. Moreover, SNHG7 was enriched in BMSCsderived exosomes (BMSCs-Exos) and could be internalized by chondrocytes. Functional analysis illustrated that BMSCsExos administration repressed inflammatory injury, oxidative stress and ferroptosis in IL-1b-induced chondrocytes, while these changes were reinforced when SNHG7 was overexpressed in BMSCs-Exos. Notably, FSP1 silencing in chondrocytes abolished the beneficial effects mediated by exosomal SNHG7. CONCLUSIONS Exosomal SNHG7 released from BMSCs inhibited inflammation and ferroptosis in IL-1b-induced chondrocytes through miR-485-5p/FSP1 axis. This work suggested that BMSCs-derived exosomal SNHG7 would be a prospective target for OA treatment.