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

Dysfunction of anti-tumor immune responses is crucial for cancer progression. Immune checkpoint blockade (ICB), which can potentiate T cell responses, is an effective strategy for the normalization of host anti-tumor immunity. In recent years, immune checkpoints, expressed on both tumor cells and immune cells, have been identified; some of them have exhibited potential druggability and have been approved by the US Food and Drug Administration (FDA) for clinical treatment. However, limited responses and immune-related adverse events (irAEs) cannot be ignored. This review outlines the development and applications of ICBs, potential strategies for overcoming resistance, and future directions for ICB-based cancer immunotherapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoplasms/drug therapy* ; Immunotherapy/methods* ; Animals

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective To explore the guiding significance of preoperative 3D reconstruction for pulmonary nodule location and thoracoscopic surgical method selection in lung cancer patients. Methods The clinical data of the patients with preoperative 3D reconstruction in our China-Japan Friendship Hospital between January and November 2023 were retrospectively analyzed. Preoperative surgical planning was performed using 3D reconstruction. Different surgical procedure, including wedge resection, segmentectomy, lobectomy, or combined surgical procedure were performed based on tumor location, size and distance from the pleura. Results A total of 115 patients were included with 45 males and 70 females, at an average age of 25-84 (58.29±11.36) years and successfully completed the operation. Fifty-five (47.8%) patients' nodule diameter was tangent cross-section, among whom twenty-five (21.7%) patients of nodules crossed sections. There were 21 patients of wedge resection in the outer 1/3 nodules of CT, which had shorter operation time and less cost (P<0.001) and less intraoperative bleeding (P=0.019). For the crossing sections or edge crossing sections nodules of the middle and inner of CT, 6 patients were of simple pulmonary segmentectomy, 8 patients of combined with sub-segmentectomy, 7 patients of combined segmentectomy, 5 patients of lobectomy, and 3 patients of wedge resection. Conclusion The proportion of cross-segment pulmonary nodules is relatively high. For the outer 1/3 nodules of CT, compared with pulmonary segmental resection combined with adjacent lung tissue resection, wedge resection can also ensure sufficient surgical margin, and the middle and inner 1/3 nodules of CT need to be combined with adjacent pulmonary tissue resection to ensure the surgical edge.

Objective:To investigate the correlation of relative cross-sectional area of lumbar paravertebral muscle and psoas with lumbar curvature and its clinical significance.Methods:This study was conducted as a retrospective cross-sectional study. Among the patients treated at the Department of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January to April 2023, 107 middle-aged and young patients with changes in lumbar physiological curvature or no apparent abnormalities were included in this study based on MRI findings. The relative cross-sectional area (RCSA) values of the left and right paravertebral muscles and psoas were measured at the lower margin of the L3 vertebral body and at the L3/L4, L4/L5, and L5/S1 intervertebral discs. Furthermore, the correlation between these RCSA values and lumbar curvature was analyzed.Results:The 107 patients were (30.51 ± 4.64) years old, and the proportion of females accounted for 71.96%. There were differences in RCSA between the lower margin of L3, L3/L4, L4/L5, and L5/S1 intervertebral discs (left psoas F = 30.21, P < 0.001; right psoas F = 31.63, P < 0.001; left paravertebral muscle F = 31.04, P < 0.001; right paravertebral muscle F = 26.55, P < 0.001). From L3 to S1, the RCSA of the psoas increased, while the RCSA of the paravertebral muscle decreased. The RCSA values of the total paravertebral muscle/RCSA values of the total psoas major muscle were positively correlated with lumbar curvature at the lower margin of the L3 vertebral body ( r = 0.40, P < 0.001). This correlation could be seen at both L3/L4 ( r = 0.31, P = 0.001) and L4/L5 ( r = 0.24, P = 0.012). However, after considering the influence of left and right muscle groups on lumbar curvature, there was no correlation between the muscle cross-sectional area at the L5/S1 disc position and lumbar curvature ( P > 0.05). Nevertheless, there was still a correlation between the muscle cross-sectional area at other lumbar segments ( P < 0.05). Conclusion:An increase in the RCSA of the psoas relative to the paraspinal muscle may lead to straightening of the lumbar spine curvature, whereas an increase in the RCSA of the paraspinal muscle relative to the psoas may result in an increase in lumbar spine curvature. Improving the quality of the paraspinal muscle may restore the physiological curvature of the lumbar spine, which holds clinical application value.

Objective:To understand the real experience of caregivers of children with craniopharyngioma-associated hypothalamic obesity (CP-HO) based on the chronic disease trajectory model, so as to provide a reference for formulating corresponding disease management plans.Methods:From May 2023 to July 2023, semi-structured interviews were conducted with 17 caregivers of children with CP-HO who were admitted to the Department of Neurosurgery, Nanfang Hospital, Southern Medical University through purposive sampling. The interview data were analyzed by Colaizzi 7-step analysis method.Results:The 17 caregivers of children with CP-HO were 24 to 46 years old, including 3 males and 14 females. A total of 3 themes were extracted. Prodromal phase of weight: lack of disease cognition and weakening of self-concept; during the period of weight increase, the demand burden became prominent and the life pattern changed; weight stability: pressure, hope, and insight into the value of life.Conclusions:For promoting a good disease response of caregivers and improving the weight management effect of children and the quality of family life, medical staff should pay attention to and understand the disease care experience of children with CP-HO, and provide comprehensive and systematic solution strategies.

Objective:To explore whether lung microorganisms influence the occurrence and development of early lung adenocarcinoma by analyzing the presence and changes of local microorganisms in early lung adenocarcinoma.Methods:Tumor tissues and alveolar lavage fluid were collected from 32 patients diagnosed with lung adenocarcinoma at the China-Japan Friendship Hospital. Nextseq550DX was used for DNA sequencing. R language was used to calculate the number of microorganisms in the tumor tissue and alveolar lavage fluid samples of different stages and grades. species and diversity, and use statistical methods such as TSEA and LEfSe analysis to compare the diversity and differences of microorganisms in different groups. Results:Both Actinobacteria and Proteobacteria accounted for a higher proportion in both the tumor tissue and alveolar lavage fluid samples of patients with lung adenocarcinoma. The number of microorganisms detected in the tumor tissue was greater than that in the lavage fluid, and the alpha diversity was higher, but the difference Not significant( P<0. 05). According to the analysis of differences in lung microorganisms in patients with different pathological grades: In the two samples, invasive adenocarcinoma has more microorganisms than carcinoma in situ + microinvasive carcinoma, and the alpha diversity of the lavage fluid is significantly higher, and the comparison between the groups is statistically significant( P=0. 011); the difference in β diversity was not statistically significant( P>0. 05). Group analysis based on different pathological types: the invasive adenocarcinoma group samples showed a decrease in Proteobacteria, the carcinoma in situ + minimally invasive cancer group was mainly composed of Proteobacteria, and most of the microorganisms related to lung cancer differences analyzed in each group belonged to Proteobacteria and Actinobacteria. Phylum. Conclusion:Most of the microbes in tumor tissues and lavage fluid of lung adenocarcinoma belong to the Actinobacteria and Proteobacteria. Most of the differentially associated microbes of lung cancer under different classifications also belong to Proteobacteria and Actinobacteria, which are the main characteristics of lung microbial composition in patients with early-stage lung adenocarcinoma.

Objective To objectively classify cancer-related fatigue(CRF)patients with qi and blood deficiency syndrome;To explore possible enrichment characteristics;To provide ideas for precise population identification.Methods A cross-sectional study was conducted,611 CRF patients with qi and blood deficiency syndrome were included from October 2019 to April 2022.Clinical symptoms of patient were documented,including pale or withered-yellow complexion,shortness of breath with reluctance to talk,dizziness,spontaneous sweating,and palpitations.Additionally,blood routine were conducted,including white blood cell(WBC)count,red blood cell(RBC)count,hemoglobin(HGB),platelet(PLT)count,and neutrophil count(NEUT).The degree of fatigue was assessed using the Piper Fatigue Scale(PFS).Data analysis was performed using R 4.2.0.Clustering analysis was performed using the K-mediods method.Results Through unsupervised clustering analysis,the target population was divided into three categories:qi and blood deficiency syndrome leaning towards qi deficiency,qi and blood deficiency syndrome with mild symptom,qi and blood deficiency syndrome leaning towards blood deficiency.In terms of fatigue severity,the first two groups showed comparable levels,while the third group exhibited the most severe fatigue.Regarding objective indicators,the group leaning towards qi deficiency had the lowest WBC count,NEUT count and PLT count,and the group leaning towards blood deficiency had the lowest HGB count and RBC count.The group of qi and blood deficiency syndrome with mild symptom exhibited the highest level of objective indicators among the three.Conclusion By using clustering analysis methods,the study has preliminarily achieved population enrichment and classification based on syndromes,providing ideas for subsequent information enrichment and accurate identification of populations.Concurrently,the anemia index,WBC count and NEUT count demonstrate a inclination towards blood deficiency syndrome and qi deficiency syndrome,respectively.These findings indicate that these indicators could be incorporated into the syndrome diagnostic criteria for CRF to aid in the classification of the CRF population.

Objective To investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1+.Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital.The patients were divided into chemotherapy group and transplant group according to treatment style.The differences of OS and PFS between the two groups were compared,and the influencing factors of prognosis of transplant patients were analyzed.Results ASXL1+ was detected in 75 patients(30.36%),with a median mutation ratio of 42.93(18.10,58.39)%,10 received supportive treatment,43 received demethylation therapy or demethylation combined with pre-excitation therapy,and 22 received allo-HSCT.2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P<0.05).The 2-year OS rate in the low ASXL1 mutation load group(VAF≤42.93%)was significantly higher than that in the high ASXL1 mutation load group(VAF>42.93%)(P<0.05).In the context of allo-HSCT in patients with ASXL1+,2-year OS and PFS rates were significantly reduced in patients with RUNX1+ or ASXL1+(P<0.05);Multivariate analysis showed that high mutation load of ASXL1 or U2AF1+ were independent risk factors for OS in transplant patient(P<0.05).U2AF1+ were the risk factors for PFS(P<0.05).Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1+ MDS.High ASXL1 mutation load or U2AF1+ were independent risk factors affecting the outcome of allo-HSCT.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.