BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Objective:To develop one kind of alarm system with pressure sensor,so as to prevent compression injuries of patients with upper limb dysfunction due to the movement of the examination bed during computed tomography(CT)examination.Methods:The alarm system with pressure sensor was constructed on the basis of Arduino UNO open-source main control board and the HX711 weighing module.The Arduino E3 power supply module was used to provide power for system,and ESP8266 main control board was used to realize remote alarm,and its 3 dimension(3D)printed customized shell can directly be installed at the edge of examination bed.A total of 228 patients with upper limb dysfunction who underwent CT examination at Xianxian County Hospital of TCM during July 2022 and October 2022 were selected.They were randomly divided into observation group and control group by using a computer-generated random number sequence.The observation group was monitored for possibly potential compression risks on upper limb of patients by using the alarm system with pressure sensor.The patients of control group were respectively accompanied by one accompanying personnel to go into the scanning room,and they wore lead aprons,lead skirts,and other protective appliances for radiation protection.When a patient is found to be at risk of being crushed,an alarm should be raised by calling a halt.The valid alarm rates of the two alarm methods were calculated.Results:There were 37 times of alarm in observation group in examination,and 31 times were valid alarms and 6 times were invalid alarms in them.In control group,there were 49 times of alarm from accompanying personnel,and 29 times were valid alarms and 20 times were invalid alarms in 49 times of alarm.The valid alarm rate of observation group was significantly higher than that of control group,and the difference was statistically significant(x2=6.048,P<0.05).Conclusion:The installation of alarm system with pressure sensor is easy,and its use is convenient,and it has a higher valid alarm rate during CT examination,and it can effectively protect patients to prevent compression injuries.

Objective:To explore the capability of deep learning image reconstruction (DLIR) compared to adaptive statistical iterative reconstruction (ASiR-V) in improving the image quality and myocardial edge sharpness of dynamic stress myocardial CT perfusion imaging (CTP).Methods:Thirty subjects who underwent dynamic stress myocardial CTP at Guangdong Provincial People′s Hospital from September 2023 to February 2024 were recruited. Image data of all enrolled patients were reconstructed using ASiR-V 50%, ASiR-V 80%, medium-intensity DLIR(DLIR-M), and high-intensity DLIR(DLIR-H), respectively. Regions of interest were selected in the left ventricular cavity, interventricular septum, and left ventricular lateral wall for measurement of CT values and standard deviations (SD), and calculation of signal to noise ratio (SNR) and contrast to noise ratio (CNR). Matlab was utilized to obtain the differences (d) and slopes (s) of CT value changes at four left ventricular myocardial edges for objective edge sharpness evaluation. Two radiologists subjectively scored the images for noise, natural appearance, and edge sharpness. In case of disagreement between the two radiologists, a third senior radiologist′s score was decisive. Left ventricular myocardial blood flow (MBF) of ASiR-V and DLIR images with lower SD, higher SNR and CNR were calculated, respectively. When the normal distribution was satisfied, the independent sample t test was used for comparison between two groups, and the random block design ANOVA was used for comparison between multiple groups. And analysis was conducted using Friedman test for non-normally distributed data, and Bonferroni correction for pairwise comparisons. Results:There were statistically significant differences in SD, SNR, and CNR among the four images in the interventricular septum and left ventricular lateral wall (all P<0.05), with ASiR-V 80% and DLIR-H demonstrating the lowest SD, highest SNR and CNR, and the subjective image noise score. Statistically significant differences were observed in d and s for the four left ventricular myocardial edges (all P<0.05), with DLIR-M and DLIR-H exhibiting the best objective edge sharpness [5 (5, 5)], and ASiR-V 80% the worst [3.5 (3, 4)]. In the subjective scores for natural appearance, DLIR-M and DLIR-H received the highest scores [5 (5, 5)], while ASiR-V 80% received the lowest scores [3 (3, 4)], with statistically significant differences (all P<0.05). There was no statistically significant difference in MBF values calculated from ASiR-V 80% and DLIR-H images (all P>0.05). Conclusions:The SD value, SNR and CNR of dynamic stress myocardial CTP images reconstructed by DLIR-H are equivalent to ASiR-V 80%, and using DLIR-H can improve the edge sharpness of left ventricular myocardium without affecting the calculation of MBF.

Objective To identify potential biomarkers for proliferative diabetic retinopathy(PDR)using proteomics and transcriptomics data.Methods In this study,the proteomics dataset(PXD046630)and two transcriptomics datasets(GSE60436 and GSE102485)were derived from the aqueous humor samples and fibrovascular membranes of PDR patients,respectively.Differentially expressed genes(DEGs)were identified via R software,specifically the limma and edgeR pack-ages.The shared DEGs between PXD046630 and GSE60436 were analyzed via protein-protein interaction(PPI),Gene On-tology(GO)enrichment,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.The key DEGs were validated in GSE102485 via receiver operating characteristic(ROC)curve analysis.A quantitative polymerase chain reaction(qPCR)assay was used to confirm the mRNA of these candidate biomarkers in human retinal microvascular endothelial cells(HRMECs)cultured in high glucose and low oxygen conditions.Results A total of 59 shared DEGs and 26 hub genes were identified from the PXD046630 and GSE60436 datasets.KEGG analysis revealed that six pathways,inclu-ding extracellular matrix-receptor interaction,proteoglycans in cancer,and complement and coagulation cascades,were enriched in 12 key DEGs.Fibronectin 1(FN1),tissue inhibitor of metalloproteinase 3(TIMP3),complement factor H(CFH),decorin(DCN),and lipoprotein receptor-related protein-2(LRP2)were identified as potential biomarkers on the basis of their AUC values being greater than 0.900(CI≥95％).The mRNA expression levels of FN1,CFH,and LRP2 were significantly increased in HRMECs cultured in high glucose and low oxygen conditions.Conclusion FN1,CFH,and LRP2 are potential biomarkers for PDR,and further studies are needed to explore their roles and therapeutic potential in PDR.

Objective:To investigate the association between magnesium sulfate exposure within 24 h before birth and short-term outcomes in preterm infants under 34 weeks' gestation.Methods:This retrospective cohort study analyzed data from preterm infants under 34 weeks admitted to the neonatal intensive care unit of the Affiliated Hospital of Qingdao University between June 1, 2020, and December 31, 2024. Infants were categorized into the exposure and the control groups based on magnesium sulfate administration within 24 hours before delivery. Maternal characteristics, birth parameters, and neonatal outcomes were compared using independent t-tests or Chi square tests (Fisher's exact test), with logistic regression assessing magnesium sulfate's effect on non-cerebral palsy outcomes. Results:The cohort comprised 384 preterm infants (24-33 +6 weeks), with 290 (75.5%) in the exposure group and 94 (24.5%) in the control group. (1) Baseline characteristics showed no significant differences in maternal hypertensive disorders, antenatal corticosteroids administration, premature rupture of membranes, delivery mode, or male infant proportion (all P>0.05). The exposure group had lower birth weight [(1 583±451) vs. (1 744±473) g; t=2.97] and gestational age [(31.3±2.1) vs.(31.8±2.4) weeks; t=2.20; both P<0.05)]. (2) The exposure group demonstrated reduced incidence of in-hospital mortality [0.3% (1/290) vs. 6.4% (6/94); Fisher's exact test], grade Ⅲ-Ⅳ intracranial hemorrhage [1.7% (5/290) vs. 9.6% (9/94); χ2=12.86], and white matter injury [2.1% (6/290) vs. 9.1% (8/94); χ2=9.08] (all P<0.01). (3) Univariate logistic regression identified antenatal magnesium sulfate as protective against grade Ⅲ-Ⅳ intracranial hemorrhage ( OR=0.20, 95% CI: 0.04-0.96), white matter injury ( OR=0.11, 95% CI: 0.01-0.91), and in-hospital mortality ( OR=0.93, 95% CI: 0.88-0.99). (4) Multivariate analysis confirmed the independent protective effect of antenatal exposure of magnesium sulfate against intracranial hemorrhage in preterm infants under 34 weeks ( OR=0.19, 95% CI: 0.04-0.95), particularly pronounced in infants <32 weeks ( OR=0.11, 95% CI: 0.01-0.96). (5) No significant differences emerged in secondary outcomes including 5-minute Apgar scores, respiratory distress syndrome, surfactant administration, mechanical ventilation, bronchopulmonary dysplasia, hemodynamically significant patent ductus arteriosus, necrotizing enterocolitis, early-onset sepsis, retinopathy of prematurity, metabolic bone disease, or hospitalization duration (all P>0.05). Conclusions:Magnesium sulfate exposure within 24 hours before delivery reduces grade Ⅲ-Ⅳ intracranial hemorrhage risk in preterm infants under 34 weeks, with enhanced protection in those <32 weeks, without increasing adverse effects in other organ systems.

Objective:To investigate the effects of acute sleep deprivation (ASD) on hippocampal glucose metabolism and neuroinflammation in rat models.Methods:Twenty SD rats (10 males and 10 females) were divided into four groups (five in each group) by random sampling method: female ASD group, male ASD group, female control group, and male control group. Among them, the ASD group constructed the ASD model. After 72h sleep deprivation, all rats underwent 18F-FDG and N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) microPET/CT brain imaging in 2d to compare the changes of 18F-FDG and 18F-DPA-714 SUV mean in the hippocampus of rats. Brain histopathology, immunohistochemistry and immunofluorescence staining were detected in rats. Independent-sample t test was used to analyze the data. Results:18F-FDG imaging showed the hippocampal SUV mean between ASD group and control group (female: 4.11±0.35 vs 1.89±0.28; male: 3.43±0.47 vs 2.02±0.54) were statistically significant ( t values: 9.65, 3.92, P values: <0.001, 0.002). 18F-DPA-714 imaging showed the hippocampal SUV mean between ASD group and control group (females: 0.28±0.01 vs 0.28±0.02; male: 0.26±0.02 vs 0.31±0.04) were not statistically significant ( t values: -0.18, -2.24, P values: 0.859, 0.056). The 18×10 3 translocator protein (TSPO) immunohistochemistry showed the expression in the hippocampal region of the brain between ASD group and control group (female: 0.19±0.02 vs 0.19±0.01; male: 0.21±0.01 vs 0.20±0.01) were not statistically different ( t values: -0.48, -1.67, P values: 0.651, 0.139). Immunofluorescence staining showed that microglial cytosol in the hippocampal region of the brain decreased after 72h of ASD, and the protrusion points and surrounding branches were significantly reduced. Conclusion:Increased hippocampal glucose metabolism in rats is observed after 72 h of ASD without significant neuroinflammation.

Thermal ablation, an established minimally invasive technique, is increasingly utilized in treating thyroid nodules and microthyroid papillary carcinoma.Compared to conventional surgery, it offers advantages including minimal trauma, rapid recovery, and fewer complications.Recent technological advances have revealed its potential for managing primary hyperthyroidism. This review examines current evidence on thermal ablation applications in hyperthyroidism, analyzes its efficacy and safety, and discusses future challenges to inform clinical practice and research.

Objective A Nomogram model of cognitive frailty was constructed and validated in hospitalized older adults,providing a reference for early screening,intervention and personalized management of cognitive frailty.Methods A convenience sampling approach was employed to recruit 322 elderly inpatients from a tertiary hospital in Beijing between October 2024 and February 2025 as study participants,and data were collected using the General Information Questionnaire,the Short Form-Mini-Nutritional Assessment,the Asens Insomnia Scale,the Activity of Daily Living Rating,the Self-Rating Anxiety Scale,the Geriatric Depression Scale-15,the Social Support Rating Scale,the Frailty Phenotype scale,the Subjective Cognitive Decline Questionnaire-9,the Mini-Mental State Examination,and the Clinical Dementia Rating.Lasso-Logistic regression was used to screen the variables,R software was used to draw the nomogram model;Bootstrap method was used for internal validation.Results Lasso-Logistic regression screened 8 predictors of age,depression,anxiety,support utilization,nutritional status,literacy,physical activity,and chronic pain,with an area under the subject operating characteristic curve of 0.830(95％CI:0.787-0.873),a sensitivity of 0.764,a specificity of 0.730,an accuracy of 0.748,and a calibrated curve,Brier score,and Hosmer-Lemeshow test(P=0.774)all showed that the model fit was good.Conclusion The Lasso-Logistic regression-based nomogram model of cognitive frailty in hospitalized older adults has good predictive performance and clinical utility,and can be used as a reference for early identification and intervention of cognitive decline in hospitalized older adults.

In the context of medical insurance payment reform,the sample hospital has implemented performance management optimization to effectively address the challenges posed by diagnosis-intervention packet(DIP)payment.Reform measures focused on disease quality,rational diagnosis and treatment,operational management,medical technological value,and policy orientation,and they have significantly optimized service ability and performance evaluation indexes of the hospital.Main achievements included a reduction in the cost consumption index and an increase in the clinical performance index,with the overall DIP payment rate increasing from 88.86%to 103.23%and a marked improvement in operational management.The quality control and operational efficiency of the hospital have been effectively enhanced by choosing proper DIP payment evaluation indexes and improving performance management,and provided strong support for the high-quality development of the hospital.

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.