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BACKGROUND: Cancer-associated fibroblasts (CAFs) play a significant role in regulating the clinical outcome and radiotherapy prognosis of prostate cancer (PCa). The aim of this study is to identify CAFs-related genes (CAFsRGs) using single-cell analysis and evaluate their potential for predicting the prognosis and radiotherapy prognosis in PCa. METHODS: We acquire transcriptome and single-cell RNA sequencing (scRNA-seq) results of PCa and normal adjacent tissues from The GEO and TCGA databases. The "MCPcounter" and "EPIC" R packages were used to assess the infiltration level of CAFs and examine their correlation with PCa prognosis. ScRNA-seq and differential gene expression analyses were used to extract CAFsRGs. We also applied COX and LASSO analysis to further construct a risk score (CAFsRS) to assess biochemical recurrence-free survival (BRFS) and radiotherapy prognosis of PCa. The predictive efficacy of CAFsRS was evaluated by ROC curves and subgroup analysis. Finally, we integrated the CAFsRS gene signature with relevant clinical features to develop a nomogram, enhancing the predictive accuracy. RESULTS: The abundance of CAFs is associated with a poor prognosis of PCa patients. ScRNA-seq and differential gene expression analysis revealed 323 CAFsRGs. After COX and LASSO analysis, we obtained seven CAFsRGs with prognostic significance (PTGS2, FKBP10, ENG, CDH11, COL5A1, COL5A2, and SRD5A2). Additionally, we established a risk score model based on the training set (n = 257). The ROC curve was used to confirm the performance of CAFsRS (The AUC values for 1, 3 and 5-year survival were determined to be 0.732, 0.773, and 0.775, respectively.). The testing set (n = 129), GSE70770 set (n = 199) and GSE116918 set (n = 248) revealed that the model exhibited exceptional predictive performance. This was also confirmed by clinical subgroup analysis. The violin plot demonstrated a statistically significant disparity in the CAFs infiltrations between the high-risk and low-risk groups of CAFsRS. Further analysis confirmed that both CAFsRS and T stage were independent prognostic factors for PCa. The nomogram was then established and its excellent predictive performance was demonstrated through calibration and ROC curves. Finally, we developed an online prognostic prediction app ( https://sysu-symh-cafsnomogram.streamlit.app/ ) to facilitate the practical application of the nomogram. CONCLUSIONS: The prognostic prediction risk score model we constructed could accurately predict BRFS and radiotherapy prognosis PCa, which can provide new ideas for clinicians to develop personalized PCa treatment and follow-up programs.

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PURPOSE: Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. METHODS: We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK-PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. RESULTS: CD8+ T cells, PD-L1+ cells, and PANCK-PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK-PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). CONCLUSIONS: Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK-PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

Assuntos

Assuntos

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OBJECTIVE: The aim of this study was to analyze the effect of tirofiban on new cerebral microhemorrhage after mechanical thrombectomy in patients with acute ischemic stroke. METHODS: In total, 203 patients with acute ischemic stroke treated by mechanical thrombectomy in our department of neurology were enrolled as the research objects. The patients were divided into two groups: the patients who used tirofiban within 24 h after surgery were assigned to the study group (78 subjects), while patients who did not use tirofiban were assigned to the conventional group (125 subjects). Magnetic resonance imaging was used to detect new-onset cerebral microbleeds in patients with stroke after surgery. The National Institute of Health Stroke Scale, modified ranking scale, and activity of daily living scale were used to assess the prognosis of patients, and the general data and the occurrence of adverse effects between two groups were compared to comprehensively evaluate the efficacy and safety of tirofiban. RESULTS: The proportion of atrial fibrillation in the research group was significantly lower than that in the conventional group. The research group had a much lower rate of new-onset cerebral microbleeds than the conventional group (p<0.001). There was no significant difference in the proportion of adverse reactions between the two groups (p>0.05). CONCLUSION: The application of tirofiban in mechanical thrombectomy of patients with acute ischemic stroke has high safety, effectively reduces the occurrence of new cerebral microhemorrhage, and provides a guarantee for patient safety.

Assuntos

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OBJECTIVES: To investigate the diagnosis and treatment of tibial intercondylar chondroblastoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 12 patients with tibial intercondylar chondroblastoma admitted to the orthopedics department from May 2011 to February 2016; among them were 4 males and 3 females aged 10-19 years, with an average age of 15.7 years. Tibial intercondylar chondroblastoma was on the left and right side in 7 and 5 cases, respectively. The preoperative average Lysholm score of the knee joint was 68 (42-87). A posteromedial approach was applied in all cases. The incisions were approximately 5-8 cm in length. Complete curettage and inactivation were performed after fenestration, and allogeneic bone grafts were transplanted. Then, the posterior cruciate ligament insertion was fixed with 5.0 suture anchors. All patients were followed up with regularly to monitor for tumor recurrence, observe bone graft healing, and reassess the Lysholm score of the knee. RESULTS: Patients were followed for 7-55 months, and the median follow-up time was 19 months. One patient experienced tumor relapse 4 months after the operation. Incision, inactivation and cementation were performed. Then, the bone was fixed with anchors. In the other 11 patients, the bone graft healed over an average period of 6.2 months (4-10 months), with good functional recovery postoperatively. The average postoperative Lysholm score of the knee was 91 (81-95). CONCLUSION: Tibial intercondylar chondroblastoma has unique clinical and imaging characteristics and can effectively be treated by curettage followed by the inactivation, transplantation and fixation of allogeneic bone grafts with suture anchors through a posteromedial approach.

Assuntos

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PURPOSE: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). METHODS: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. RESULTS: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). CONCLUSION: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Assuntos

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Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P 0.01), while PaO2 was significantly reduced (P 0.01). The apoptosis index was significantly increased (P 0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P 0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.(AU)

Assuntos

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Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Assuntos

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OBJECTIVES: To investigate the diagnosis and treatment of tibial intercondylar chondroblastoma. METHODS: We retrospectively analyzed the diagnosis and treatment of 12 patients with tibial intercondylar chondroblastoma admitted to the orthopedics department from May 2011 to February 2016; among them were 4 males and 3 females aged 10-19 years, with an average age of 15.7 years. Tibial intercondylar chondroblastoma was on the left and right side in 7 and 5 cases, respectively. The preoperative average Lysholm score of the knee joint was 68 (42-87). A posteromedial approach was applied in all cases. The incisions were approximately 5-8 cm in length. Complete curettage and inactivation were performed after fenestration, and allogeneic bone grafts were transplanted. Then, the posterior cruciate ligament insertion was fixed with 5.0 suture anchors. All patients were followed up with regularly to monitor for tumor recurrence, observe bone graft healing, and reassess the Lysholm score of the knee. RESULTS: Patients were followed for 7-55 months, and the median follow-up time was 19 months. One patient experienced tumor relapse 4 months after the operation. Incision, inactivation and cementation were performed. Then, the bone was fixed with anchors. In the other 11 patients, the bone graft healed over an average period of 6.2 months (4-10 months), with good functional recovery postoperatively. The average postoperative Lysholm score of the knee was 91 (81-95). CONCLUSION: Tibial intercondylar chondroblastoma has unique clinical and imaging characteristics and can effectively be treated by curettage followed by the inactivation, transplantation and fixation of allogeneic bone grafts with suture anchors through a posteromedial approach.

Assuntos