Copper death plays a significant regulatory role in biological processes. An increasing number of studies have revealed the mechanism, function, and potential clinical application value of copper death in bladder cancer. The emergence of copper death can provide new ideas for the treatment of bladder cancer. This article summarizes the role and regulation mechanism of copper death in bladder cancer, and reviews the research progress of copper-related proteins, copper death-related signaling pathways, copper nanoparticles, and copper carriers in bladder cancer, which is expected to provide new ideas and directions for the treatment of bladder cancer.

Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective : To develop and to validate a combined model integrating18F-FDG PET/CT radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia. Methods : A retrospective study was conducted on a cohort of 232 patients diagnosed with lymphoma or lymphoid inflammatory hyperplasia. Comparative analyses of clinical and traditional imaging indicators were performed to identify inter-group differences. The clinical features were delineated and extracted using medical software including 3D-Slicer and Lifex. Selection of the features was performed to construct a PET/CT-based radiomics Logistic model, with a combined model integrating PET/CT with clinical features then used to evaluate the discriminative efficacy of these models. Results: Analysis of inter-group differences indicated that age, CTmean, and metabolic tumor volume(MTV)were effective for differentiating between lymphoma and lymphoid inflammatory hyperplasia(P<0.05). The PET/CT-based radiomics Logistic model differentiated between lymphoma and lymphoid inflammatory hyperplasia, with an area under curve(AUC) of 0.924(95%CI: 0.884-0.960) and 0.863(95%CI: 0.774-0.939) in the training and testing cohorts, respectively. The integrated Logistic model that combined PET/CT-based radiomics with clinical features to distinguish between lymphoma and lymphoid inflammatory hyperplasia achieved an AUC of 0.933(95%CI: 0.889-0.969) in the training cohort and 0.884(95%CI: 0.792-0.964) in the testing cohort. Decision curve analysis(DCA) demonstrated that the integrated model provided the greatest clinical net benefit. Conclusion The hybrid model integrating18F-FDG PET/CT radiomics with clinical features shows robust diagnostic efficacy to distinguish between lymphoma and lymphoid inflammatory hyperplasia.

Objective To evaluate the diagnostic value of endobronchial ultrasound-transvascular needle aspiration(EBUS-TVNA)in hilum of lung and mediastinal lesions.Methods 10 cases of hilum of lung and mediastinal lesions who underwent EBUS-TVNA because vessels pass between the airway and lesions were selected from June 2021 to January 2023,the diagnostic rate and complications were retrospectively analyzed.Results Of the 10 patients,8 traversed the pulmonary artery or its branches,2 traversed aorta or superior vena cava.Specimens were successfully obtained from all patients and 8 of them got definitive diagnosis,including 6 malignancy and 2 benign lesions.The overall yield of EBUS-TVNA for hilum of lung and mediastinal lesions was 80.0%(8/10),the diagnostic sensitivity for malignancy was 85.7%(6/7),and the diagnostic specificity was 100.0%(3/3).The other 2 cases were not diagnosed,1 was diagnosed as bladder urothelial carcinoma by percutaneous lung puncture biopsy,and the other was classified as benign due to the reduced lesion after 6 months of follow-up.All of them had good tolerance to the operation,and no serious complications occurred.Conclusion EBUS-TVNA is a safe and effective technique for the diagnosis of hilum of lung and mediastinal lesions,it can be used as an effective auxiliary method to traditional ultrasound bronchoscopy techniques.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

Objective:To investigate the application value of three-dimensional (3D) recons-truction combined with endoscopic ultrasonography (EUS) in preoperative accurate evaluation of biliary tract neoplasms.Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of 19 patients with biliary tract neoplasms who underwent 3D reconstruction combined with EUS in the Shangdong Provincial Third Hospital from January 2019 to October 2022 were collected. There were 13 males and 6 females, aged 64(range, 35-75)years. All patients underwent preoperative abdominal enhanced computer tomography (CT) thin-slice scan with 3D reconstruction combined with EUS. Some patients further received other endoscopic techniques such as intraductal ultrasonography, endoscopic retrograde cholangiopancreatography or SpyGlass cholangioscopy to obtain tumor tissues for histopathology evaluation. The surgical implementation protocol was developed based on the results of 3D reconstruction and EUS. Observation indicators: (1) results of 3D reconstruction; (2) results of EUS; (3) comparison between preoperative surgical protocol and actual intraoperative conditions. Measurement data with skewed distribution were represented as M(range), and count data were described as absolute numbers and/or percentages. Results:(1) Results of 3D reconstruction. Results of 3D reconstruction in 19 patients with biliary tract neoplasms showed morphology of the liver, bile ducts, pancreas, blood vessels, and duodenum, including 4 cases of hilar cholangiocarcinoma, 14 cases of middle and lower cholangiocarcinoma, and 1 case of intrahepatic cholangiocarcinoma. The accuracy of 3D reconstruction in 19 patients was 18/19. (2) Results of EUS. All 19 patients underwent preoperative EUS, including 7 cases obtained tumor tissue for histopathology evaluation, with the results indicating abnormal hyperplasia or malignant tumor. The rate of histopathology evaluation was 7/19, with the sensitivity as 7/7. Of 19 patients, results of EUS in 2 cases indicated positive of lymph node metastasis, but results of postoperative histopathology evaluation indicated negative of lymph node metastasis in lymph node specimens. Results of EUS in the rest of 17 cases indicated negative of lymph node metastasis, but results of intraoperative laparoscopic exploration on 1 case indicated extensive intra-abdominal metastasis. (3) Comparison between preoperative surgical protocol and actual intraoperative conditions. Of 19 patients, 18 cases underwent radical resection and 1 case underwent bile duct drainage, with the compliance rate between preoperative surgical protocol and actual intraoperative conditions as 18/19. The volume of intraoperative blood loss in the 18 cases receiving radical resection was 336(range, 50-1500)mL. Two cases had postoperative complications.Conclusion:Results of 3D reconstruction combined with EUS can accurately map the the size, location, extent of bile duct invasion, and adjacent relationships of surrounding tissues of malignant biliary tract neoplasms, for preoperative accurate evaluation and surgical planning.

Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P＜0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) ％ in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

Objective To investigate the antitumor mechanism of astragaloside combine with cetuximab on the colon cancer cell line RKO of EGFR over expression through cell proliferation and autophagy. Methods The cell proliferation of colon cancer cell line RKO intervened by astragaloside with or without cetuximab was detected by 4- methyl- teerazolium (MTT). The expressive changes for protein of EGFR 、P62 and LC3 in RKO cells was detected by western bolt. Results MTT showed that 100 ug/mL astragaloside combined with 120 ug/mL cetuximab had significantly inhibiting effect on RKO cells of EGFR expression. Western blot showed that astragaloside can affect the expression of P62 and LC3 to suppress the occurrence ofautophagy. Conclusion In the vitro studies showed that astragalosidecan enhance the antitumor cell proliferation of cetuximab through inhibit autophagy in the treatment of colon cancer.

BACKGROUND:With the increasing of aging, the incidence and mortality of osteoporotic hip fracture wil rise. It is of great significance to study the pathogenesis and preventing method. At present, finite element analysis can be used to judge fracture, only for the distribution trend of fracture failure in the starting point or section view, but it cannot completely reflect actual situation of fracture. OBJECTIVE:To build the fracture model of the femoral neck fracture caused by fal ing-induced external force based on the finite element analysis LS-DYNA software, and to evaluate the effect of rupture. METHODS:CT image data of one case of elderly femoral neck fracture were col ected. Using Mimics software, region growth of the contralateral area, cavity fil ing, editing, rebuilding the contralateral proximal femur model were conducted. Data were imported in Hypermesh and LS-DYNA software for meshing, and defining material properties. The failure parameters and interfacial properties were set. The load and force boundary constraints simulating the fal ing were simulated. The model of femoral neck fracture was calculated. Rupture effect was evaluated. RESULTS AND CONCLUSION:(1) The validity of contralateral proximal femur three-dimensional model was verified. Based on the finite element analysis software LS-DYNA, the femoral neck fracture model matched the actual fracture line to a degree of close to 83%. (2) Above results confirmed that based on the finite element analysis, LS-DYNA software can wel simulate the femoral neck fracture, which provides experimental basis to the exploration of femoral neck fracture classification mechanism caused by different fal ing-induced external forces.