The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Objective:To investigate whether the image quality of total-body PET/CT (TB PET/CT) with 1 min acquisition can meet the clinical diagnostic requirements.Methods:From May 2019 to September 2021, a total of 90 malignant tumor patients (60 males, 30 females, age 31-86 years) with primary lesions confirmed by pathological diagnosis in Zhongshan Hospital, Fudan University were respectively analyzed. All patients underwent conventional PET/CT (C PET/CT) scan with conventional clinical acquisition and TB PET/CT scan with 1 min acquisition after injecting 18F-FDG in random order. Paired t test or Wilcoxon signed rank test was used to analyze the image quality of these two scans. Results:SUV max of primary lesions in TB PET/CT group was significantly higher than that in C PET/CT group (15.9(7.9, 24.6) vs 12.5(5.8, 16.6); z=8.14, P<0.001), so were signal-to-noise ratio (SNR) of the blood pool, liver, muscles (9.3±3.0, 11.4(9.5, 14.2), 8.3(7.3, 10.1) vs 6.2±1.7, 9.4(7.7, 11.8), 6.0(4.9, 7.1)), tumor-to-blood pool ratio (TBR) (9.3(4.3, 14.8) vs 8.5(4.3, 11.1)), tumor-to-liver ratio (TLR) (6.7(3.0, 10.4) vs 6.1(2.9, 7.7)), tumor-to-muscle ratio (TMR) (23.2(11.5, 38.0) vs 18.3(9.6, 26.6); t=9.36, z values: 4.44-7.40, all P<0.001). Conclusion:The image quality of TB PET/CT scan with 1 min acquisition can meet the diagnostic requirements, and is better than the C PET/CT image quality with conventional clinical acquisition.

68Ga-DOTATATE/18F-FDG two-day low-dose total-body PET/CT imaging is increasingly employed to facilitate the diagnosis,prognosis,and heterogeneity assessment of neuroendocrine neoplasms.We present a consensus on operational guideline for a two-day combined imaging from experts in low-dose/ultra-low-dose total-body PET/CT from several domestic medical institutions.

Objective:To develop a simple, rapid, and convenient analysis method for the identification of breast cancer and its molecular sub-types.Methods:A laser confocal Raman spectrometer was used to collect Raman spectrograms of normal breast cells and different molecular sub-types of breast cancer cells, and assign the material origin of the Raman spectral peaks. First, Savitzky-Golay smoothing (with a window size of 9) was selected to perform smoothing and denoising on the Raman spectrogram. Subsequently, an iterative adaptive weighted penalty least squares method was employed for baseline correction, and principal component analysis was used to eliminate outliers. The recognition model of normal breast cells and breast cancer cells and the recognition model of different molecular sub-types of breast cancer cells were established by using three algorithms with different principles, including partial least squares discriminant analysis (PLS-DA), K-nearest neighbor (KNN), and support vector machine (SVM).Results:The Raman spectrogram and Raman peak shifts of normal breast cells and breast cancer cells were similar, but there were significant differences in intensity. The results of the machine learning models showed that the recognition accuracy of PLS-DA and SVM algorithms for distinguishing between normal breast cells and breast cancer cells was above 92.03% and 90.67%, respectively. The recognition accuracy of PLS-DA and SVM algorithms for different molecular sub-types of breast cancer cells was (83.66 ± 2.77)% and (90.55 ± 0.06)%, respectively.Conclusions:The combination of Raman spectroscopy and machine learning algorithms can achieve accurate identification of normal breast cells, breast cancer cells, and different molecular sub-types of breast cancer cells.

Animals ; Monkeypox/drug therapy* ; Antiviral Agents/therapeutic use* ; Phosphoric Monoester Hydrolases/therapeutic use* ; Macaca fascicularis

Blast injury of the chest injury is the most common wound in modern war trauma and terrorist attacks, and is also the most fatal type of whole body explosion injury. Most patients with severe blast injury of the chest die in the early stage before hospitalization or during transportation, so first aid is critically important. At present, there exist widespread problems such as non-standard treatment and large difference in curative effect, while there lacks clinical treatment standards for blast injury of the chest. According to the principles of scientificity, practicality and advancement, the Trauma Society of Chinese Medical Association has formulated the guidance of classification, pre-hospital first aid, in-hospital treatment and major injury management strategies for blast injury of the chest, aiming to provide reference for clinical diagnosis and treatment.

Objective:To investigate the effect of sleeve gastrectomy on blood glucose in obese rats with diabetes mellitus.Methods:Thirty-two 12 week old Goto Kakizaki (GK) diabetic rats were randomly divided into 4 groups: sham operation group (A) , sleeve stomach operation group (B) , sleeve stomach operation+external bile drainage group (C) and sleeve stomach operation + external bile drainage + oleanolic acid group (D) . The changes of fasting blood glucose and blood bile acid were compared before and after operation. The expression level of GLP-1 in serum of each group was detected by ELISA, and the difference of protein expression of bile acid G protein coupled receptor (TGR5) was detected by Western blot.Results:The blood glucose level of group A had no significant change after operation. But blood glucose level in group B and group D was significantly lower than that before operation. Blood glucose in group C was lower than that before operation, but there was no significant difference in comparison. Serum total bile acid level in group A had no significant difference before and after operation. Bile acid level in group B was significantly higher than that before operation, while bile acid level in group C and group D was significantly lower than that before operation. There was no significant difference in the level of serum GLP-1 in group A before and after operation. The level of serum GLP-1 in group B and group D was significantly higher than that before operation. The level of serum GLP-1 in group C was lower than that before operation, but there was no significant difference. The expression of TGR5 protein in terminal ileum in group B and group D was higher than that in group A, but the expression in group C was similar with that in group A.Conclusions:Sleeve gastrectomy has definite hypoglycemic effect on T2DM rats. Bile acid and its related receptor TGR5 should play an important role in the mechanism of sleeve gastrectomy in treatment of diabetes.

OBJECTIVE: To study the anti- fibrotic effect of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) and explore the mechanism. METHODS: Twenty-four C57 BL/6 mice were divided into 4 groups (=6), including the control group treated with intratracheal injection of saline (3 mg/kg); lung fibrosis model group with intratracheal injection of 1.5 mg/mL bleomycin solution (prepared with saline, 3 mg/kg); EXOs1 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the next day after modeling); and EXOs2 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the 10th day after modeling). At 21 days after modeling, pulmonary index, lung tissue pathology and collagen deposition in the mice were assessed using HE staining and Masson staining. The expression level of TGF-β1 was detected using ELISA, and vimentin, E-cadherin and phosphorylated Smad2/3 (p-Smad2/3) were detected using immunohistochemical staining. CCK8 assay was used to evaluate the effect of hUCMSCEXOs on the viability of A549 cells, and Western blotting was used to detect the expression levels of p-Smad2/3, vimentin, and E-cadherin in the cells. RESULTS: Compared with those in the model group, the mice treated with hUCMSC-EXOs showed significantly reduced the pulmonary index ( < 0.05), collagen deposition, lung tissue pathologies, lowered expressions of TGF-β1 ( < 0.05), vimentin, and p-Smad2/3 and increased expression of E-cadherin. hUCMSC-EXOs given on the second day produced more pronounced effect than that given on the 11th day ( < 0.05). CCK8 assay results showed that hUCMSC-EXOs had no toxic effects on A549 cells ( > 0.05). Western blotting results showed that hUCMSC-EXOs treatment significantly increased the expression of E-cadherin and decreased the expressions of p-Smad2/3 and vimentin in the cells. CONCLUSIONS hUCMSC-EXOs can alleviate pulmonary fibrosis in mice by inhibiting epithelialmesenchymal transition activated by the TGF-β1/Smad2/3 signaling pathway, and the inhibitory effect is more obvious when it is administered on the second day after modeling.
Animals ; Epithelial-Mesenchymal Transition ; Exosomes ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Mesenchymal Stem Cells ; cytology ; Mice ; Pulmonary Fibrosis ; therapy ; Transforming Growth Factor beta1 ; genetics ; Umbilical Cord ; cytology

OBJECTIVE: To study the anti- fibrotic effect of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) and explore the mechanism. METHODS: Twenty-four C57 BL/6 mice were divided into 4 groups (=6), including the control group treated with intratracheal injection of saline (3 mg/kg); lung fibrosis model group with intratracheal injection of 1.5 mg/mL bleomycin solution (prepared with saline, 3 mg/kg); EXOs1 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the next day after modeling); and EXOs2 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 μg/250 μL, given by tail vein injection on the 10th day after modeling). At 21 days after modeling, pulmonary index, lung tissue pathology and collagen deposition in the mice were assessed using HE staining and Masson staining. The expression level of TGF-β1 was detected using ELISA, and vimentin, E-cadherin and phosphorylated Smad2/3 (p-Smad2/3) were detected using immunohistochemical staining. CCK8 assay was used to evaluate the effect of hUCMSCEXOs on the viability of A549 cells, and Western blotting was used to detect the expression levels of p-Smad2/3, vimentin, and E-cadherin in the cells. RESULTS: Compared with those in the model group, the mice treated with hUCMSC-EXOs showed significantly reduced the pulmonary index ( < 0.05), collagen deposition, lung tissue pathologies, lowered expressions of TGF-β1 ( < 0.05), vimentin, and p-Smad2/3 and increased expression of E-cadherin. hUCMSC-EXOs given on the second day produced more pronounced effect than that given on the 11th day ( < 0.05). CCK8 assay results showed that hUCMSC-EXOs had no toxic effects on A549 cells ( > 0.05). Western blotting results showed that hUCMSC-EXOs treatment significantly increased the expression of E-cadherin and decreased the expressions of p-Smad2/3 and vimentin in the cells. CONCLUSIONS hUCMSC-EXOs can alleviate pulmonary fibrosis in mice by inhibiting epithelialmesenchymal transition activated by the TGF-β1/Smad2/3 signaling pathway, and the inhibitory effect is more obvious when it is administered on the second day after modeling.
Animals ; Epithelial-Mesenchymal Transition ; Exosomes ; Humans ; Mesenchymal Stem Cells ; Mice ; Pulmonary Fibrosis ; Transforming Growth Factor beta1 ; Umbilical Cord

Objective To evaluate a model for axillary lymph node involvement combining CK19 mRNA with contrast enhanced ultrasound sonography (CEUS) score in operable breast cancer.Methods Operable breast cancer patients planned for sentinel lymph node (SLN) biopsy were enrolled.Preoperative CK19mRNA expressions in peripheral blood and CEUS score of axillary lymph nodes were tested before surgery.In the training set,postoperative sentinel lymph node (SLN) and non-sentinel lymph node (nSLN) pathological results were taken as the gold standard,effective modeling variables were screened,logistic regression was used to establish the prediction model.Parallel control studies were conducted between the validation set and the MSKCC model to evaluate the prediction accuracy and prediction efficiency.Results From Oct 2015 to Nov 2016,359 cases (training set) were enrolled and mathematical formulas for predicting SLN and nSLN were established,respectively.The sensitivity,specificity and AUC of predicting SLN involvement were 91.36％,94.92％ and 0.979 respectively.The sensitivity,specificity and AUC of predicting nSLN metastasis were 91.04％,90.53％ and 0.932 respectively.From Dec 2016 to Jul 2017,219 cases (verification set) were included.The sensitivity of SLN metastasis predicted by the model was 91.84％,the specificity was 96.69％,and the AUC was 0.979,significantly superior to the MSKCC model (0.739).The sensitivity,specificity and AUC of predicting nSLN metastasis were 95.35％,92.73％ and 0.945 respectively,significantly superior to the MSKCC model (0.873).Concolusions Combined with peripheral blood CK19 mRNA and CEUS score,the prediction model for axillary lymph node involvement for operable breast cancer,SLN/nSLN involvement probability can be calculated and qualitative judgment can be made.The overall accuracy and AUC of this model are better than the prediction model of MSKCC.