Background and purpose:Relapsed or refractory diffuse large B-cell lymphoma(DLBCL)can be treated with chimeric antigen receptor T-cell(CAR-T)therapy.Imaging-based biomarkers may help identify patients likely to achieve clinical response to this immunotherapy.In this study,an 18-f1uoro-2-deoxy-D-glucose positron emission tomography-computed tomography(18F-FDG PET/CT)based model was developed to assess the progression-free survival(PFS)and overall survival(OS)of patients with relapsed or refractory(R/R)DLBCL who received CAR-T therapy.Methods:We retrospectively analyzed clinical and imaging data from patients with DLBCL who underwent CAR-T therapy at the First Affiliated Hospital of Soochow University between March 2017 and January 2022.Inclusion criteria:① age≥18 years old;② pathologically confirmed R/R DLBCL;③ 18F-FDG PET/CT performed before CAR-T cell therapy;④ complete clinicopathologic data;⑤ patients must have measurable lesions.Exclusion criteria:① patients with incomplete clinical or imaging data;② patients with other types of malignant tumors;③ patients who have received granulocyte colony-stimulating factor treatment within 1 month prior to PET/CT scan.This study was reviewed by the Ethics Committee of the First Affiliated Hospital of Soochow University(ID:2025256).Receiver operating characteristic(ROC)curves were used to determine the optimal thresholds for maximum standardized uptake value(SUVmax),tumor metabolic volume(MTV),and total glycolysis(TLG),and the patients were classified into high-risk and low-risk groups.Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors and construct predictive models,which were visualized by drawing nomogram.Area under the ROC curve was used to assess the performance of each model.Results:A total of 61 patients(37 male patients and 24 female patients,aged 26-75 years)with DLBCL who underwent 18F-FDG PET/CT prior to CAR-T infusion were included.The median follow-up was 14 months;36 patients(59.02%)had disease progression and 25 patients(40.98%)died.Multivariate analysis showed that grade of cytokine release syndrome(CRS)[Hazard ratio(HR)=3.671;P=0.003]and MTV(HR=0.171,P=0.004)were independent prognostic factors for OS;Eastern Cooperative Oncology Group(ECOG)score(HR=2.411,P=0.019),grade of CRS(HR=2.499;P=0.027),and MTV(HR=0.338,P=0.007)were independent prognostic factors for PFS.The combined model(MTV,ECOG score,grade of CRS)was better than the clinical model(ECOG score,grade of CRS),and metabolic parameter model(MTV)in predicting PFS and OS.Conclusion:18F-FDG PET/CT metabolic parameter MTV in combination with traditional clinical risk factors(ECOG score,Grade of CRS)could identify patients with ultra-high risk of DLBCL.

Background and purpose:Relapsed or refractory diffuse large B-cell lymphoma(DLBCL)can be treated with chimeric antigen receptor T-cell(CAR-T)therapy.Imaging-based biomarkers may help identify patients likely to achieve clinical response to this immunotherapy.In this study,an 18-f1uoro-2-deoxy-D-glucose positron emission tomography-computed tomography(18F-FDG PET/CT)based model was developed to assess the progression-free survival(PFS)and overall survival(OS)of patients with relapsed or refractory(R/R)DLBCL who received CAR-T therapy.Methods:We retrospectively analyzed clinical and imaging data from patients with DLBCL who underwent CAR-T therapy at the First Affiliated Hospital of Soochow University between March 2017 and January 2022.Inclusion criteria:① age≥18 years old;② pathologically confirmed R/R DLBCL;③ 18F-FDG PET/CT performed before CAR-T cell therapy;④ complete clinicopathologic data;⑤ patients must have measurable lesions.Exclusion criteria:① patients with incomplete clinical or imaging data;② patients with other types of malignant tumors;③ patients who have received granulocyte colony-stimulating factor treatment within 1 month prior to PET/CT scan.This study was reviewed by the Ethics Committee of the First Affiliated Hospital of Soochow University(ID:2025256).Receiver operating characteristic(ROC)curves were used to determine the optimal thresholds for maximum standardized uptake value(SUVmax),tumor metabolic volume(MTV),and total glycolysis(TLG),and the patients were classified into high-risk and low-risk groups.Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors and construct predictive models,which were visualized by drawing nomogram.Area under the ROC curve was used to assess the performance of each model.Results:A total of 61 patients(37 male patients and 24 female patients,aged 26-75 years)with DLBCL who underwent 18F-FDG PET/CT prior to CAR-T infusion were included.The median follow-up was 14 months;36 patients(59.02%)had disease progression and 25 patients(40.98%)died.Multivariate analysis showed that grade of cytokine release syndrome(CRS)[Hazard ratio(HR)=3.671;P=0.003]and MTV(HR=0.171,P=0.004)were independent prognostic factors for OS;Eastern Cooperative Oncology Group(ECOG)score(HR=2.411,P=0.019),grade of CRS(HR=2.499;P=0.027),and MTV(HR=0.338,P=0.007)were independent prognostic factors for PFS.The combined model(MTV,ECOG score,grade of CRS)was better than the clinical model(ECOG score,grade of CRS),and metabolic parameter model(MTV)in predicting PFS and OS.Conclusion:18F-FDG PET/CT metabolic parameter MTV in combination with traditional clinical risk factors(ECOG score,Grade of CRS)could identify patients with ultra-high risk of DLBCL.

Background::Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors.Methods::The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020.Results::The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy.Conclusions::We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

Melanoma is the most aggressive cutaneous tumor. Neuropilin and tolloid-like 2 (NETO2) is closely related to tumorigenesis. However, the functional significance of NETO2 in melanoma progression remains unclear. Herein, we found that NETO2 expression was augmented in melanoma clinical tissues and associated with poor prognosis in melanoma patients. Disrupting NETO2 expression markedly inhibited melanoma proliferation, malignant growth, migration, and invasion by downregulating the levels of calcium ions (Ca²⁺) and the expression of key genes involved in the calcium signaling pathway. By contrast, NETO2 overexpression had the opposite effects. Importantly, pharmacological inhibition of CaMKII/CREB activity with the CaMKII inhibitor KN93 suppressed NETO2-induced proliferation and melanoma metastasis. Overall, this study uncovered the crucial role of NETO2-mediated regulation in melanoma progression, indicating that targeting NETO2 may effectively improve melanoma treatment.
Humans ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Cell Line, Tumor ; Cell Proliferation ; Melanoma/genetics* ; Membrane Proteins/genetics* ; Phosphorylation ; Signal Transduction

Thymic neuroendocrine tumors (TNETs) are a series of rare diseases with aggressive biology and poor prognosis. Clinical manifestations of TNETs are atypical, and ectopic secretion of adrenocorticotropic hormone can be found in some cases, resulting in associated endocrine symptoms. Due to the low morbidity and strong heterogeneity, it’s difficult to diagnose, treat and obtain new treatment regimen. Early complete surgical resection is an effective treatment. For advanced cancer, clinical trials of new drugs are expected to improve the survival of patients.

Building a professional clinical research team inside hospitals is in favor improving their research abilities,accelerating the clinical discipline construction,improving their comprehensive influence.Also it fits the objective of general hospital development under gate-keeping system.Now in domestic,the percentage of professional research staff in large hospitals accounts was much less than the international level.The main reasons included the misunderstanding of constructing the research-oriented hospitals,insufficient human resources enrollment,less attractive environment to the highlevel researchers and the absence of relevant degree training programs.To enhance the construction of research-oriented hospitals,it's of key importance to build the professional research team in hospitals.Besides,the hospital has to update management conception,broaden the channels of talent cultivation,grasp the development of the subject accurately and interact with the basic medicine and public health subject,increase the financial investment and perfect the relevant management regulations.