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 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.

Objective To observe the incidence and prognosis of respiratory failure in patients after cardiac surgery,and the risk factors were analyzed.Methods A total of 559 patients who underwent cardiac surgery were enrolled in Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from July 2020 to November 2023.Clinical data were extracted through the hospital information system(HIS).This included general data such as gender,age,body mass index(BMI),smoking history,alcohol history,comorbidities,and basic disease data like occurrence of respiratory tract infection in the past 1 month before surgery,preoperative use of antimicrobial drugs,ejection fraction,operation time,cardiopulmonary bypass time,intraoperative blood transfusion,nasogastric tube indwelling,nosocomial infection,secondary thoracotomy,preoperative white blood cell count(WBC),length of intensive care unit(ICU)stay,secondary intubation and tracheostomy,discharge diagnosis,and outcome.The patients were divided into two groups according to whether or not they had expiratory failure.The difference of the above data between the two groups was compared.Multivariate Logistic regression was used to analyze the risk factors of respiratory failure in patients after cardiac surgery,the prediction model was constructed based on the above risk factors,and the receiver operator characteristic curve(ROC curve)was drawn to analyze the predictive value of the prediction model for patients with respiratory failure.Results The incidence of respiratory failure in patients after cardiac surgery was 7.51%(42 cases).Multivariate Logistic regression analysis showed that intraoperative blood transfusion>2000 mL,nasogastric tube,and nosocomial infection were risk factors for respiratory failure in patients after cardiac surgery[odds ratio(OR)and 95%confidence interval(95%CI)were 4.136(1.794-9.535),3.162(1.454-6.878)and 3.488(1.262-9.638),all P<0.05].The ROC curve analysis showed that the prediction model had a certain predictive value for the occurrence of respiratory failure in patients after cardiac surgery[area under the curve(AUC)=0.738,95%CI was 0.658-0.818,P<0.001].The length of ICU stay of patients in the group with respiratory failure was significantly longer than that in the group without respiratory failure(hours:8.16±7.62 vs.4.52±3.95),the secondary intubation rate[80.95%(34/42)vs.0(0/517)]and the tracheostomy rate[88.10%(37/42)vs.0(0/517)]were significantly higher than those in the non-respiratory failure group,and the recovery/improvement rate was significantly lower than that in the non-respiratory failure group[59.52%(25/42)vs.90.13%(466/517)],the differences were statistically significant(all P<0.05).Conclusions Patients with intraoperative blood transfusion>2000 mL,nasogastric tube inserted,and nosocomial infection are the high-risk groups for respiratory failure after cardiac surgery.Medical staff should strengthen the identification of high-risk groups and actively take intervention measures to improve the prognosis of patients.

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.

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.

In order to cultivate qualified oral clinicians, strengthen examination management, and strictly implement process assessment, Special Training Base of Oral and Maxillofacial Radiology in West China Hospital of Stomatology, Sichuan University, has implemented a whole-process and diversified assessment reform. In the part of process assessment, firstly the students were asked to fill in the workload form to give timely feedback on training and truly reflect attendance records; secondly, the performance of trainees in class was comprehensively evaluated in clinical training and theoretical teaching to improve their ability of comprehensive thinking of clinical problems. In the part of result assessment, the traditional theoretical assessment method was weakened, and the ability of comprehensive clinical research was strengthened. Trainees were guided to choose the topic flexibly and use standardized PPT format, and a comprehensive score was determined after assessment. Experts were invited to give their advice, so as to enhance the clinical confidence and scientific research confidence of trainees and help them expand their learning depth and breadth within the limited training time. The analysis of examination methods and assessment results shows that the "whole-process and diversified" assessment mode can truly reflect the training results of trainees and lay a solid foundation for further improvement and implementation of standardized training.

Objective:To investigate the effect of Clostridium butyricum on renal tissue of db/db mice and to explore its mechanism. Methods:Fourteen-week-old db/db mice were divided into db/db group( n=10) and db/db+ Cb group( n=7) according to random number table method. Age-matched db/m mice were selected as the normal control group. The db/m and db/db mice were administered 0.9% sodium chloride solution by gavage, while the db/db+ Cb mice were administered an equivalent amount of Clostridium butyricum solution by gavage for 8 weeks. Serum creatinine , fasting blood glucose, urinary albumin to creatinine ratio(ACR) and other biochemical indicators were also detected. HE staining was used to observe the pathological changes of kidney tissue. The expressions of peroxisome proliferators-activated receptor γ coactivator-1α(PGC-1α) mRNA were detected by realtime PCR, while the expressions of nuclear factor-κB(NF-κB), glucagon-like peptide 1 receptor(GLP-1R), and adenosine monophosphate-activated protein kinase(AMPK) in kidney tissue were determined by immunohistochemistry and Western blotting. The levels of intestinal flora, serum and fecal short-chain fatty acids(SCFAs) were measured by 16S rRNA, liquid chromatograph-mass spectrometer, and gas chromatograohy-mass spectrometry respectively. Results:Compared to db/db mice, db/db+ Cb mice showed improvement in general condition after supplementation with Clostridium butyricum. Fasting blood glucose, blood urea nitrogen, albumin-to-creatinine ratio(ACR), blood creatinine, and levels of interleukin-6(IL-6) in kidney tissue were reduced(all P<0.05). The pathology showed various degrees of amelioration of kidney tissue injury in mice. The expression of PGC-1α mRNA increased in kidney tissue( P<0.05). Decreased expression of NF-κB protein, as well as increased expression of GLP-1R and phosphorylated(p-)AMPK/AMPK protein(all P<0.05) were detected in kidney tissues. Clostridium butyricum modulated the composition of the gut microbiota with elevated total SCFAs in blood and feces. Conclusion:Clostridium butyricum increased the expression of GLP-1R in kidney tissue, promoted AMPK phosphorylation, and alleviated renal tissue damage in mice. This suggests that it may be associated with regulating the abundance of SCFA-producing bacterial populations.