ABSTRACT
Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.
ABSTRACT
To realize dynamic and standardized periodical quality control of medical equipment. A set of auto reminder module for medical equipment quality control was established by using the user-defined flow of medical equipment operation maintenance system, and the continuous improvement was realized for medical equipment quality control in some hospital. Dynamic medical equipment quality control was formed from the static one, so that the efficiency of medical equipment quality control was enhanced greatly. References were provided for other hospitals in dynamic and informatzied medical equipment quality control and testing.
ABSTRACT
Objective To explore the relationship between methylenetetra hydrofolate reduetase (MTHFR) C677T genotypo and unstable angina pectoris(UA) in Chinese population. Methods The study consisted of 90 UA cases (UA group), and an age- and sex- matched healthy control cases (control group, n = 90). PC R-RFLP was used to analyze polymorphism of the MTHFR C677T genotypo. The relationship between MTHFR C677T genotype and UA was observed. Results MTHFR 677C→T mutation was found in 30 of 90 patients with unstable angina pectoris (33.33%) and in 15 of 90 control subjects (16.67%). This difference was statistically significant (P<0.05). Conclusion MTHFR 677C→T mutation is closely related to the unstable angina poctoris.
ABSTRACT
Objective To evaluate the effects of different interventios on insulin resistance and ?-cell function in population with impaired glucose tolerance(impaired glucose tolerance,IGT).Methods The total of 382 cases of IGT were divided into five groups according to interventions:control(C),diet plus exercise group(D+E),Acarbose Group(A),Metformin(M)and traditional Chinese medicine Group(TCM),with each group making the appropriate intervention programmes.BMI,FPG,2hPG,F-Ins,P-Ins,F-CP and P-CP were determined before intervention and yearly during the follow up,and BMI,HOMA-IR,HOMA-? were calculated.Results By the end of the study,insulin,F-CP,IR Group D+E and FPG,2hPG,insulin,C-peptide,IR in the other groups were significantly lower than before the intervention(P
