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 investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To analyze the differences in clinical outcomes and toxicities between postoperative radiotherapy alone and postoperative radiochemotherapy for soft tissue sarcoma (STS), as well as the related factors affecting clinical prognosis of STS patients.Methods:Retrospective analysis of patients diagnosed with primary STS admitted to Zhejiang Cancer Hospital from May 2012 to May 2019 was performed, who received adjuvant radiotherapy after surgery, combined with or without postoperative chemotherapy. A total of 100 patients were enrolled and divided into postoperative radiotherapy group ( n=52) and postoperative radiochemotherapy group ( n=48). The median follow-up time was 65 months (24-124 months). The local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-related toxicities were recorded in two groups. The survival rate was calculated by Kaplan-Meier analysis. Log-rank test was used for univariate analysis, and Cox model was used for multivariate analysis. Results:In multivariate analysis, the maximum tumor diameter was an independent predictor of local tumor recurrence ( HR=4.80, 95% CI=1.16-19.85, P=0.031), distant metastasis ( HR=4.67, 95% CI=1.53-14.26, P=0.007) and OS ( HR=4.10, 95% CI=1.35-12.48, P=0.013). In addition, the degree of myelosuppression in patients in postoperative radiochemotherapy was significantly higher than that in their counterparts in postoperative radiotherapy group ( P<0.001). Conclusions:In the limited number of patients, radiochemotherapy has no advantages over radiotherapy alone in distant metastasis or survival rate. Besides, it increases toxicities, but the overall tolerability is favorable. It is necessary to conduct prospective randomized studies in a large population and subgroup analysis of histological subtypes, aiming to obtain results with better reference value.

OBJECTIVE: To evaluate the effects of ginsenosides (GSS) extracted from ginseng stem and leaves on glucocorticoid receptor (GR) in different viscera in heat-damaged rats, and to find out its action mechanism. METHODS: Thirty-two male SD rats were divided into control group and experimental group, and fed 2 mg/d GSS and equal-quantity of distilled water respectively for 7 days. Eight rats of each group were exposed to (42+/-1) degrees C for one hour. The binding activities of GR in brain, thymus, lung and liver cytosols in rats were detected by radioligand binding assay. The expression levels of GR mRNA in brain and liver cytosols were determined by reverse transcription-polymerase chain reaction (RT-PCR) assay. Plasma adrenocorticotropin (ACTH) and corticosterone (CS) concentrations were determined by radioimmunoassay. RESULTS: The binding activities of GR in brain, lung and liver cytosols, and the expression levels of GR mRNA in brain and liver cytosols were all higher in the GSS-treated and heat-damaged rats than those in the untreated heat-damaged rats (P<0.05 or P<0.01). There were no significant differences in plasma concentrations of ACTH and CS between the GSS-treated heat-damaged rats and the untreated heat-damaged rats. CONCLUSION: GSS can lessen the descending degree of the binding activity of GR in brain, thymus, lung and liver cytosols, and such efficacy of GSS may be related to improvement of the expression of GR mRNA.

In teaching the course of Environmental Hygiene to the senior major of the four-year undergraduates of the Department of Public Administration,we have tried to reform the teaching program for the course of Public Place Hygiene.The related theories are taught right on the spot of public places instead of in classrooms.Students are organized to carry out such activities on their own as studying subject matters,consulting related documents and data,working out and implementing programs for on-the-spot monitoring and inspection,and then exchanging and discussing the results of monitoring and inspection,so that their interest in the courses is increased and their understanding of what they have learned is deepened.In this way they are able to apply their knowledge to practice,improve their practical capabilities,and enhance their overall capacity for analyzing and finding solutions to problems they are faced with.

Object To evaluate the effects of ginsenosides (GSS) in stem and leaves of ginseng on glucocorticoid receptor (GR) in the hemorrhagic shock rats, and study the mechanism. Methods Rats were divided into hemorrhagic shock group and control group. The rats in hemorrhagic shock groups were ig 200, 100, 50 mg/kg/d GSS, model group and control group were ig distilled water 2 mL for 10 days. The Rs of GR in brain and hepatic cytosol of rats were measured by radioligand binding assay, using [ 3H] dexamethasone as the ligand. The level of GR mRNA expression in hepatic cytosol were determined by RT-PCR. Plasma adrenocorticotrophic hormone (ACTH) and glucocorticoid (GC) concentrations were determined by the radioimmunoassay. Results Rs of GR in brain and hepatic cytosol were higher in hemorrhagic shock+GSS groups than those in hemorrhagic shock group, and the Rs of GR was the highest in hemorrhagic shock+10 mg/mL GSS group (P