Objective: To investigate the preventive and reparative mechanisms of platelet-rich plasma-biodegradable quick setting spray (PRP-BQSS) on solar dermatitis, thereby providing a safe and effective novel therapeutic approach for clinical application. Methods: PRP-BQSS was prepared. A ultraviolet B (UVB)-induced solar dermatitismodel was established in SPF-grade male SD rats. The rats were divided into the prevention experiment (treated with PRP-BQSS, L' Oréal SPF 50+sunscreen, Nature's Hall SPF 50+sunscreen, or saline) and the treatment experiment (treated with PRP-BQSS, Jingwanhong ointment, Green ointment, or saline). The effects were evaluated by measuring epidermal thickness (HE staining) and quantifying the integrated optical density (IOD) of inflammatory cells (CD11b staining). One-way ANOVA and Tukey's HSD test were performed using GraphPad Prism 9.4.0. Results: The PRP-BQSS exhibited significant efficacy in both prevention and repair. In the prevention experiment, the PRP-BQSS prevention group (Group A) showed only mild pale red erythema on the dorsal skin of rats, without significant swelling or desquamation. Histological analysis revealed that epidermal thickness in Group A (36.55±6.58 μm) was comparable to Groups B (L' Oréal, 34.84±6.59 μm) and C (Natural Hall, 34.59±8.20 μm)(P>0.05), but significantly lower than that in Group D (control group, 47.82±11.69 μm). Skin sections from Group A demonstrated intact epidermal structure with clear stratification and no significant inflammatory cell infiltration. The CD11b-positive cell count (24.30±7.43) was significantly lower than that in Group D (33.65±8.47, P<0.05). In the treatment experiment, HE staining of Group A (PRP-BQSS treatment group) showed intact epidermal structure with orderly arrangement of the basal layer, spinous layer, and granular layer, thin and uniform stratum corneum, and regular collagen fiber arrangement. The epidermal thickness of Group A (37.10±6.41 μm) showed no significant difference from Groups B (Jingwanhong ointment group, 38.66±9.07 μm) or C (Green ointment group, 35.72±4.98 μm)(P>0.05), but was significantly lower than that in Group D (control group, 48.35±8.99 μm)(P<0.05). The integral optical density value of CD11b-positive cells in Group A (32.82±11.01) was significantly lower than that in Group D (47.25±13.52, P>0.05). Moreover, the degree of inflammatory infiltration in Group A was relatively lower compared to Group B (37.14±9.20) and Group C (34.32±16.87), suggesting a superior repair capacity. However, the intergroup differences were not statistically significant (P>0.05). Conclusion: PRP-BQSS hydrogel dressing possesses dual preventive and reparative functions. It exerts its effects by reducing CD11b-positive cell infiltration (inflammation suppression) and promoting the orderly arrangement of the basal layer-epidermal layer-granular layer (epidermal reconstruction). This material holds promise as a novel and effective therapeutic approach for the prevention and treatment of solar dermatitis, particularly suitable for high-risk populations such as children, individuals with sensitive skin, and those engaged in outdoor activities.

BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

OBJECTIVES: To propose a new method for optimizing radiotherapy planning for lung cancer by incorporating prognostic models that take into account individual patient information and assess the feasibility of treatment planning optimization directly guided by minimizing the predicted prognostic risk. METHODS: A mixed fluence map optimization objective was constructed, incorporating the outcome-based objective and the physical dose constraints. The outcome-based objective function was constructed as an equally weighted summation of prognostic prediction models for local control failure, radiation-induced cardiac toxicity, and radiation pneumonitis considering clinical risk factors. These models were derived using Cox regression analysis or Logistic regression. The primary goal was to minimize the outcome-based objective with the physical dose constraints recommended by the clinical guidelines. The efficacy of the proposed method for optimizing treatment plans was tested in 15 cases of non-small cell lung cancer in comparison with the conventional dose-based optimization method (clinical plan), and the dosimetric indicators and predicted prognostic outcomes were compared between different plans. RESULTS: In terms of the dosemetric indicators, D_95% of the planning target volume obtained using the proposed method was basically consistent with that of the clinical plan (100.33% vs 102.57%, P=0.056), and the average dose of the heart and lungs was significantly decreased from 9.83 Gy and 9.50 Gy to 7.02 Gy (t=4.537, P<0.05) and 8.40 Gy (t=4.104, P<0.05), respectively. The predicted probability of local control failure was similar between the proposed plan and the clinical plan (60.05% vs 59.66%), while the probability of radiation-induced cardiac toxicity was reduced by 1.41% in the proposed plan. CONCLUSIONS The proposed optimization method based on a mixed objective function of outcome prediction and physical dose provides effective protection against normal tissue exposure to improve the outcomes of lung cancer patients following radiotherapy.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods* ; Prognosis ; Radiotherapy, Intensity-Modulated/methods* ; Carcinoma, Non-Small-Cell Lung/radiotherapy* ; Radiotherapy Dosage ; Female ; Male ; Middle Aged

OBJECTIVES: To investigate the role of apelin in regulating proliferation, migration and angiogenesis of bladder cancer cells and the possible regulatory mechanism. METHODS: GEO database was used to screen the differentially expressed genes in bladder cancer tissues and cells. Bladder cancer and paired adjacent tissues were collected from 60 patients for analysis of apelin expressions in relation to clinicopathological parameters. In cultured bladder cancer J82 cells and human umbilical vein endothelial cells (HUVECs), the effects of transfection with an apelin-overexpressing plasmid or specific siRNAs targeting apelin, fibroblast growth factor 2 (FGF2) and fibroblast growth factor receptor 1 (FGFR1) on proliferation and migration of J82 cells and tube formation in HUVECs were examined using plate cloning assay, Transwell assay, and angiogenesis assay; the changes in FGF2 expression and FGFR1 phosphorylation were detected using Western blotting. RESULTS: The expression level of apelin was significantly higher in bladder cancer tissues than adjacent tissues, and bladder cancer cell lines (T24 and J82) also expressed higher mRNA and protein levels of apelin than SV-HUC-1 cells. Apelin expression level in bladder cancer tissues was correlated with tumor invasion, distant metastasis and advanced TNM stages. Apelin knockdown significantly suppressed proliferation and migration of J82 cells and decreased the total angiogenic length of HUVECs. In contrast, apelin overexpression significantly promoted proliferation and migration and enhanced FGFR1 phosphorylation in J82 cells, and increased the total angiogenesis length in HUVECs, but this effects were effectively mitigated by transfection of the cells with FGF2 siRNA or FGFR1 siRNA. CONCLUSIONS High expression of apelin promotes J82 cell proliferation and migration and HUVEC angiogenesis by promoting activation of the FGF2/FGFR1 pathway.
Humans ; Urinary Bladder Neoplasms/blood supply* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism* ; Cell Proliferation ; Cell Movement ; Fibroblast Growth Factor 2/metabolism* ; Neovascularization, Pathologic ; Human Umbilical Vein Endothelial Cells ; Cell Line, Tumor ; Signal Transduction ; Apelin ; Intercellular Signaling Peptides and Proteins/genetics* ; Female ; Male ; Angiogenesis

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

With the widespread adoption of lung cancer screening and growing public awareness, the detection rate of pulmonary nodules has increased substantially, posing new challenges for clinical management. Artificial intelligence (AI) has emerged as a powerful tool across the entire management spectrum of pulmonary nodules. Beyond improving detection sensitivity and consistency in chest radiographs and low-dose CT, AI has demonstrated promising applications in malignancy risk assessment, molecular subtype prediction, preoperative 3D planning, intraoperative navigation, and postoperative monitoring. This review summarizes recent advances in the application of AI to pulmonary nodule screening, longitudinal evaluation, pathology prediction, multi-omics integration, and perioperative management. It also discusses the technical characteristics, clinical performance, current limitations, and future prospects of various AI models. The continuous development of AI is reshaping the clinical pathway of pulmonary nodules toward more efficient and individualized care.

Objective : To investigate the cross⁃sectional associations of serum interleukin( IL) Ⅳ18 with cartilage volume , cartilage defects , bone marrow lesions ( BML) and biomarkers of cartilage degradation in patients with knee osteoarthritis (OA) , and to provide new ideas and new methods for clinical diagnosis and treatment. Methods: The study included 151 patients with knee OA , a general questionnaire survey was conducted , and the knee strucral was photographed by magnetic resonance imaging (MRI) . The cartilage volume was measured by OsiriX software in 3D⁃FLASH sequence , and cartilage defect and BML were determined in T2⁃weighted sequence. Serum IL-18 and matrix metalloproteinase ( MMP) Ⅳ3 , 13 levels were measured by enzyme⁃linked immunosorbent assay(ELISA) . SPSS software was used for statistical analysis. Results : In multivariable analyses , serum IL⁃18 level was consistent at divided part of joint (femorotibial joint and the patella femoral joint , all P < 0. 05) . Serum IL⁃18 level was positively associated with cartilage defect and BML at media femorotibial area (all P < 0. 01) . Serum IL⁃18 level was positively associated with MMP⁃3 (β = 0. 31 , 95% CI:0. 001 - 0. 010) and MMP⁃13 (β = 0. 86 , 95% CI:0. 08 - 0. 10 , all P < 0. 01) . CI:0. 08 - 0. 10 , all P < 0. 01) . Conclusion Serum IL⁃18 level is negatively associated with cartilage volume and Serum IL⁃18 level is negatively associated with cartilage volume and positively associated with cartilage defect , BML , MMP⁃3 and MMP⁃13 , suggesting IL⁃18 may play a significant role duce the injury of article cartilage in patients with knee OA and delay the progression of disease.