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

OBJECTIVES: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Objective: To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability. Methods: From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated. Results: The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2. Conclusions Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective To retrieve,extract,evaluate,and integrate the relevant evidence of postoperative pulmonary rehabilitation management in patients with lung cancer complicated with chronic obstructive pulmonary disease,so as to provide an evidence-based basis for improving the quality of postoperative pulmonary rehabilitation.Methods Relevant literature on postoperative pulmonary rehabilitation of lung cancer complicated with chronic obstructive pulmonary disease were searched by computer from clinical decisions,guideline websites,professional association websites,and comprehensive databases.The types of the literature included clinical decisions,guidelines,expert consensuses,evidence summaries,systematic reviews,meta-analyses,and randomized controlled trials.The retrieval time limit was from the establishment of the database to September 2023.Results A total of 19 articles were included,including 4 clinical decisions,3 guidelines,6 expert consensuses,1 evidence summary,3 systematic reviews,and 2 randomized controlled trials.Through reading,extraction and classification,23 pieces of best evidence were finally formed,including multidisciplinary cooperation,evaluation,pulmonary rehabilitation strategies and health education.Conclusion This study summarizes the best evidence for postoperative lung rehabilitation management in patients with lung cancer and chronic obstructive pulmonary disease.Clinical medical staff can implement practical evidence for postoperative lung rehabilitation based on actual situations,and promote the transformation of evidence-based knowledge into practice.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status.Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research.Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance,insulin sensitivity,neck circumference(NC)and neck circumference height ratio(NHtR)in the subjects with different glucose metabolism status,the relationship between NC and insu-lin resistance and insulin sensitivity in different glucose metabolism groups.Results 171(62.9%)Subjects with diabetes were intervened by exercised every day.Spearman correlation analysis showed the correlation between exer-cise frequency and tri-glyceride triglyceride-glucose index(TyG index)(r=-0.120,P＜0.05)and NC(r=-0.168,P＜0.05)were negatively correlated.In subjects with diabetes,NC was positively correlated with triglyc-erides(TG)(r=-0.100,P＜0.05),homeostasis model assessment of insulin resistance(HOMA-R)(r=-0.163,P＜0.05),total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214,P＜0.05)and TyG index(r=-0.156,P＜0.05).Conclusions Increased frequency of exercise is associated with reduced NC,improved insulin resistance,and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes.Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.

Objective:To explore the current status of intrinsic capacity in elderly patients with hospitalization-associated disability (HAD) and explore its influencing factors.Methods:From November 2023 to January 2024, convenience sampling was used to select 203 elderly patients with HAD at Xuanwu Hospital of Capital Medical University as the study subjects. A survey was conducted on elderly patients using the General Information Questionnaire, Fried Frailty Phenotype, Barthel Index, Social Support Rating Scale, and Intrinsic Capacity Assessment Tool. Binomial Logistic regression was used to analyze the influencing factors of intrinsic capacity in elderly patients with HAD.Results:A total of 203 questionnaires were distributed, and 199 valid questionnaires were collected, with a valid response rate of 98.03% (199/203). The total score of intrinsic capacity in 199 elderly patients with HAD was 5.00 (4.00, 6.00), with scores for cognitive dimension, psychological dimension, motor dimension, vitality dimension, and sensory dimension being 1.00 (1.00, 2.00), 2.00 (1.00, 2.00), 0 (0, 1.00), 1.00 (1.00, 1.00) and 1.00 (1.00, 1.00), respectively. The binomial Logistic regression showed that department of medicine and surgery, self-rating health status, social support, serum albumin, and Barthel Index were the influencing factors of intrinsic capacity in elderly patients with HAD ( P<0.05) . Conclusions:The intrinsic capacity of elderly patients with HAD is at medium to low level, with the most severe impairment in the motor dimension. Medical and nursing staff should develop personalized rehabilitation measures for elderly HAD patients based on the influencing factors of their intrinsic capacity, enhance their intrinsic capacity, and reduce the burden of care on families and society.

Objective:To explore the current situation of ageism among older adults in megacity communities and analyze its influencing factors.Methods:From November to December 2023, convenience sampling was used to select 200 older adults who visited the Niujie Community Health Service Center in Xicheng District, Beijing as the research subject. A survey was conducted on older adults using the General Information Questionnaire, Barthel Index, 15-Item Geriatric Depression Scale, Family Adaptation, Partnership, Growth, Affection and Resolve Scale (Family APGAR Scale), Rosenberg Self-Esteem Scale, Social Support Rating Scale, Lubben Social Network Scale, and Ageism Questionnaire. Multiple linear regression was used to analyze the influencing factors of ageism among older adults in the community.Results:A total of 200 questionnaires were distributed and 200 valid questionnaires were collected, with a valid response rate of 100.00% (200/200). The total score of ageism among 200 older adults in the community was (3.55±0.31), with objective and subjective scores of (3.59±0.28) and (3.50±0.48), respectively. Multiple linear regression showed that occupational status, pre-retirement or current work, family care, self-esteem, and social support were the influencing factors of ageism among older adults in the community ( P<0.05) . Conclusions:Ageism among older adults is influenced by various factors. Medical and nursing staff should focus on older adults who are retired, mainly engaged in physical work, and have poor family and social support when formulating intervention strategies. Community health workers should regularly organize activities to encourage older adults to actively participate, enhance their sense of social participation, reduce ageism, so as to promote healthy aging.

Objective To investigate the value of T2 mapping sequence combined with apparent diffusion coefficient(ADC)values in identifying benign and malignant breast lesions.Methods Ninety-two patients with breast mass were retrospectively selected,all patients received MRI examination,T2 mapping sequence and ADC values were selected for image analysis,and all patients underwent surgical biopsy and pathological diagnosis,the clinical value of T2 mapping sequence combined with ADC values in differential diagnosis of benign and malignant breast lesions was observed.Results After pathological examination,52 patients were diagnosed as malignant breast lesions and the remaining 40 were diagnosed as benign breast lesions.Among 52 patients with malignant lesions,51 were diag-nosed as malignant and 1 was diagnosed as benign by ADC values.Among the 40 cases of benign lesions,16 were diagnosed as malig-nant and 24 were diagnosed as benign by ADC values.The difference between the mean T2 values of benign breast lesions and malig-nant breast lesions was not significant(P＞0.05);but the coefficient of variation(CV)of T2 values of malignant breast lesions was significantly higher than that of benign breast lesions,and the difference was significant(P＜0.05),and the diagnostic efficacy of T2 mapping and ADC value single examination was lower than that of the combined examination(P＜0.05).Conclusion T2 mapping sequence and ADC value in MRI have the ability to diagnose and distinguish benign and malignant breast,especially the value of the joint application of the two is more prominent,improve the diagnostic accuracy,sensitivity and specificity,and can provide more accurate reference information for clinical practice,which is worth popularizing.

Objective:To evaluate the relationship between the preoperative neutrophil/lymphocyte ratio(NLR) and postoperative delirium (POD)in elderly patients.Methods:Nine hundred and thirty-seven patients, undergoing elective knee or hip arthroplasty under combined spinal and epidural anesthesia, in whom Mini-Mental State Examination was completed at 1 day before operation, with Mini-Mental State Examination score≥24, were selected. Elbow venous blood samples were collected before surgery, neutrophils and lymphocytes were counted, and the ratio of neutrophils to lymphocytes was calculated.Cerebrospinal fluid (CSF) 2 ml was extracted after successful spinal-epidural puncture for measurement of preoperative amyloid beta40 (Aβ40), amyloid beta42 (Aβ42), total Tau (T-tau), and phosphorylated Tau (P-tau) by enzyme-linked immunosorbent assay. POD was assessed by Confusion Assessment Method, and the severity of POD was assessed by the Memorial Delirium Assessment Scale.The logistic regression equation was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. Sensitivity analysis was used to test the stability of the results. The receiver operating characteristic curve was introduced, and the area under the curve was calculated to evaluate the accuracy of preoperative NLR in predicting POD.Results:A total of 853 patients were finally enrolled in this study, and 17.4% patients developed POD. Logistic regression analysis showed that the increased levels of NLR ( OR 1.141, 95% confidence interval [ CI] 1.033-1.260, P=0.010), P-tau in CSF ( OR 1.093, 95% CI 1.076-1.110, P<0.001) and T-tau in CSF( OR 1.003, 95% CI 1.001-1.005, P<0.001) were risk factors for POD, while the increased level of Aβ42 in CSF( OR 0.998, 95% CI 0.997-1.000, P=0.028) was a protective factor for POD after adjusting for multiple confounding factors. Analysis of mediating effect: T-tau and P-tau in CSF were the mediating factors in the relationship between NLR and POD with the mediating effects of 0.011 9 and 0.020 0 respectively, and the proportion of mediating effect was 46.1% and 53.1% respectively.The receiver operating characteristic curve showed that the area under the curve of NLR and combination of NLR and CSF biomarkers in predicting POD was 0.711 and 0.939 respectively. Conclusions:Increased preoperative NLR level is a risk factor for POD, and combination of NLR and CSF biomarkers shows a higher accuracy in predicting POD. T-tau and P-tau in CSF serve as the key mediators in the relationship between NLR and POD.