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

BACKGROUND:The problem of intervertebral disc injury and degeneration has been studied in many ways.Many studies have shown that intervertebral disc injury and degeneration is driven by mechanical loading factors.However,the potential relationship between common phenotypes of intervertebral disc injury and degeneration and mechanical loading factors has been rarely summarized. OBJECTIVE:To summarize the types of common structural abnormalities exhibited by intervertebral disc injury and degeneration in the published literature,and sum up the potential links to the types of mechanical loading that lead to these structural abnormalities in in vitro and ex vivo experimental studies. METHODS:Using the terms"intervertebral disc failure,intervertebral disc injury,mechanical load,mechanical factor,load factor,biomechanics"as Chinese and English key words in PubMed,CNKI,and WanFang databases,articles related to intervertebral disc injury degeneration and mechanical load factors were retrieved.Literature screening was performed according to the inclusion and exclusion criteria,and 88 articles were finally included. RESULTS AND CONCLUSION:(1)Common structural abnormalities of intervertebral discs include decreased intervertebral disc height,disc bulge,osteophyte formation,annulus fibrosus tear,intervertebral disc herniation or disc prolapse,endplate damage,Schmorl nodes and intervertebral disc calcification.Intervertebral discs are susceptible to mechanical load types such as compression,bending,axial rotation,and compound loads.(2)The compressive load mainly causes the decrease of the proteoglycan content and the water-binding ability of the intervertebral disc,leading to the decrease or swelling of the intervertebral disc and further damage and degeneration of the intervertebral disc.In addition,the excessive compressive load causes greater damage to the endplate.(3)Bending load and axial rotation load damage the annulus fibrosus more than the endplate,and prolonged or repeated bending loads can cause tearing of the fibrous annulus and herniation or prolapse of the intervertebral disc,while pure axial rotation loads can induce less damage to the intervertebral disc and only cause the tear of the annulus fibrosus.(4)However,when different load types act in combination,it is more likely to result in high stress on the disc and a greater risk of disc injury.(5)Injury and degeneration of the intervertebral disc present progressive structural damage,and early prevention and protection are particularly important in clinical practice.Future tissue engineering research can start with early repair of the intervertebral disc.

Pregnancy ; Female ; Humans ; Pregnancy Outcome ; Cross-Sectional Studies ; Lupus Erythematosus, Systemic/epidemiology* ; Pregnancy Complications/epidemiology* ; Menstruation Disturbances

BACKGROUND:In recent years, the technical parameters about hurdle athletes are mainly obtained through video analysis and DLT algorithm. However, the gait and surface electromyography (sEMG) characteristics during normal walking are little reported. OBJECTIVE: To explore the changes of the gait and lower limb sEMG signals relative to gait period in hurdle athletes. METHODS:Eight male professional hurdlers were selected to perform gait and lower limb sEMG tests on the trail, and the differences in gait and sEMG signals were analyzed by mathematical statistics. RESULTS AND CONCLUSION: The gait parameters of hurdlers showed no significant differences (except step length). In the total gait cycle, along with the gait changing, the right and left side muscles of the same name moved alternately. The median frequency and average power frequency of the tapping leg in the lower limb muscles were greater than those of the swinging leg (except biceps femoris, tibialis anterior and lateral gastrocnemius), but the mean EMG and EMG integral values of the tapping leg were smaller than those of the swinging leg. At the stand phase, the median frequency and average power frequency of the tapping leg in the lower limb muscles were greater than those of the swinging leg (except tibialis anterior), but the mean EMG and EMG integral values of the tapping leg were smaller than those of the swinging leg (except soleus). At the swing phase, the median frequency and average power frequency of the tapping leg in the lower limb muscles were greater than those of the swinging leg (except tibialis anterior and lateral gastrocnemius), but the mean EMG and EMG integral values of the tapping leg were smaller than those of the swinging leg (except soleus). To conclude, there are different degrees of differences in the frequency domain and time domain of the lower limb muscles between tapping and swinging legs. Additionally, the muscle strength of the tapping leg is less than that of the swinging leg.

Objective To explore the diagnostic value of SPECT/CT on fracture healing.Methods A total of 28 patients (13 males,15 females; average age 45.3 years) with fracture were enrolled.All underwent metal fixation.SPECT/CT scans were performed at least 6 months after the metal fixation.X-ray examination before SPECT/CT showed equivocal fracture healing.The fracture delayed union or nonunion were judged by degree of uptake as well as uptake pattern around fracture site.Final diagnosis was confirmed by surgery or follow-up X-ray film.Results Among 28 patients,15 showed delayed union (confirmed by follow-up),and 13 showed nonunion (confirmed by surgery).There were 13 screws in 6 patients showed abnormal uptake,suggesting screw loose (confirmed by surgery).Conclusions SPECT/CT imaging could be of clinical significance in assessing fracture healing.

Objective To investigate the effects of nuclear factor κB(NF-κB) antisense oligodeoxynucleotides (AS-ODNs) on transforming growth factor β1 (TGF-β1)-induced epithelial mesenchymal transition (EMT) in human renal tubular epithelial cells. Methods NF-κB AS-ODNs were transferred into the human renal tubular epithelial cells (HK-2), and the cells were stimulated by 10 μg/L TGF-β1 for 24 hours. The expression of NF-κB mRNA and α-SMA mRNA were measured by RT-PCR. α-SMA protein expression was assessed by fluorescence spectrum.Results TGF-β1 significantly up-regulated the expression of NF-κB mRNA, which was 8 folds of blank control (P<0.01). TGF-β1-indueed epithelial mesenchymal transition was inhibited by NF-kB AS-ODN and the NF-KB mRNA expression of AS-ODNs was decreased by 75%(P<0.05).The expression of α-SMA mRNA and protein was also down-regulated obviously (P<0.05).Conclusion NF-κB AS-ODN can inhibit the expression of NF-κB and the epithelial-mesenchymal transition, which may be a new therapeutic strategy against tubulointerstitial fibrosis.