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 analyze the correlation between white blood cell(WBC)and blood cell indexes in megaloblastic anemia(MA)patients.Methods A total of 79 patients diagnosed as MA by bone marrow cell morphology at Adicon Medical Laboratory Center from June 2023 to June 2024 were included in MA group,and another 40 healthy physical examination subjects during the same period were included in health group.The levels of WBC,red blood cell(RBC),platelet(PLT),hemoglobin(Hb)and mean corpuscular hemoglobin(MCH),mean corpuscular volume(MCV)were measured and compared between two groups.Spearman correlation was used to analyze the correlation of each parameter.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of WBC in MA.Results The levels of WBC,PLT,Hb and RBC in MA group were significantly lower than those in healthy group(P＜0.05),MCH and MCV levels were significantly higher than those of healthy group(P＜0.05).WBC was positively correlated with PLT,Hb and RBC(P＜0.05),and were negatively correlated with MCH and MCV(P＜0.05).ROC curve analysis showed that the area under the curve of WBC diagnosis MA was 0.926(95％CI:0.876-0.975).The levels of PLT,Hb and RBC in severe and above group were significantly lower than those in mild to moderate group(P＜0.05).The degree of anemia in MA patients was negatively correlated with the levels of PLT,Hb and RBC(P＜0.05),and the more severe the anemia,the lower the levels of PLT,Hb and RBC.Conclusion The changes of WBC and RBC are related to the occurrence of MA,and WBC can be used as a reference index for the diagnosis of MA.

Objective To analyze the correlation between white blood cell(WBC)and blood cell indexes in megaloblastic anemia(MA)patients.Methods A total of 79 patients diagnosed as MA by bone marrow cell morphology at Adicon Medical Laboratory Center from June 2023 to June 2024 were included in MA group,and another 40 healthy physical examination subjects during the same period were included in health group.The levels of WBC,red blood cell(RBC),platelet(PLT),hemoglobin(Hb)and mean corpuscular hemoglobin(MCH),mean corpuscular volume(MCV)were measured and compared between two groups.Spearman correlation was used to analyze the correlation of each parameter.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of WBC in MA.Results The levels of WBC,PLT,Hb and RBC in MA group were significantly lower than those in healthy group(P＜0.05),MCH and MCV levels were significantly higher than those of healthy group(P＜0.05).WBC was positively correlated with PLT,Hb and RBC(P＜0.05),and were negatively correlated with MCH and MCV(P＜0.05).ROC curve analysis showed that the area under the curve of WBC diagnosis MA was 0.926(95％CI:0.876-0.975).The levels of PLT,Hb and RBC in severe and above group were significantly lower than those in mild to moderate group(P＜0.05).The degree of anemia in MA patients was negatively correlated with the levels of PLT,Hb and RBC(P＜0.05),and the more severe the anemia,the lower the levels of PLT,Hb and RBC.Conclusion The changes of WBC and RBC are related to the occurrence of MA,and WBC can be used as a reference index for the diagnosis of MA.

Objective:To investigate the application effect of high-altitude field-based teaching in acute mountain sickness.Methods:The medical students of the classes 2018 and 2019 majoring in clinical medicine were selected as subjects, and they were divided into conventional teaching group and field-based teaching group, with 20 students in each group. The students in the conventional teaching group received classroom teaching alone, and those in the field-based teaching group received high-altitude field-based teaching after theoretical lectures. The two groups were compared in terms of the theoretical knowledge of acute mountain sickness, the quality score of internship, and rescue operation score of acute mountain sickness, and questionnaire feedback and post-class discussion were performed among trainees and teachers to evaluate the high-altitude field-based teaching model. SPSS 19.0 was used for statistical analysis.Results:Compared with the conventional teaching group, the field-based teaching group had significantly higher scores of the theoretical knowledge of acute mountain sickness (91.72±4.34 vs. 86.10±5.15, P<0.001), the quality score of internship (89.64±5.21 vs. 83.51±2.38, P<0.001), and the rescue operation of acute mountain sickness [94.05 (89.54, 94.87) vs. 87.01 (84.33, 90.82), P<0.001]. Conclusions:High-altitude field-based teaching can improve the teaching effect of acute mountain sickness and cultivate the interest and learning enthusiasm of students, and therefore, it holds promise for wide application.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

To analyze the clinical features and genetic variants of a child with type 4 familial partial lipodystrophy (FPLD4) and the initial manifestation of diabetes.The male patient with the age of 13 years and 5 months, and the diabetes course was about 3 years, the patient was admitted to Children′s Hospital of Soochow University on November 10, 2021(4 th hospitalization at the hospital), in the course of diabetes, the children repeatedly suffered from diabetes ketoacidosis, and lipid metabolism complications gradually emerged.The gene sequencing showed that the proband and his mother carried dual gene mutations of PLIN1 c. 1325delG(p.G442Afs*99) and SPINK1 c. 194+ 2T>C(p.? ). The PLIN1 gene was the causal gene of FPLD4.The mutations of c. 1325delG in the PLIN1 gene had not been previously reported.Based on the clinical phenotype, family history and genetic testing findings, the patient was diagnosed as FPLD4.In addition, the mutation of SPINK1 c. 194+ 2T>C(p.? ) might increase the risk of chronic pancreatitis.This case report enriched the clinical characteristics and genotype data of FPLD4.Gene sequencing assisted the accurate diagnosis of the type of diabetes.The effects of dual gene mutations on disease progression should be concerned, which were of great significance to develop treatment regimen and disease management.

OBJECTIVE To investigate the effects of nasal administration of non-mitogenic acid fibroblast growth factor(NMFGF1) loaded nanoparticles(NMFGF1-NPs) on the improvement of cognitive function in vascular dementia(VD) mice and its mechanism. METHODS Nanoparticles containing NMFGF1(NMFGF1-NPs) were prepared by water-in-water emulsion technique and characterized. The mice were divided into sham group, VD model group, blank-NPs group, NMFGF1 solution group and NMFGF1-NPs group after repeated cerebral ischemia-reperfusion to establish VD test model, and then given the corresponding form of drug intervention by nasal cavity. After drug intervention, Morris water maze was used to evaluate the learning and memory function of the animals in each group from the perspective of behavior. Meanwhile, the morphology, arrangement and apoptosis index(AI) of hippocampal neurons in each group were evaluated by pathological methods such as HE staining, FJB staining and Tunel apoptosis staining. In addition, ELISA and Western blotting were used to investigate the molecular mechanism of NMFGF1-NPs improving VD by nasal administration. RESULTS The morphology of NMFGF1-NPs was round. The encapsulation rate of NMFGF1-NPs respectively was (87.76±5.89)%. Morris water maze results showed that the behavioral indexes of mice in VD model group were significantly different from those in sham operation group(P<0.01). At the same time, the pathological results showed that the neurons in the CA1 region of the hippocampus in the VD model group were disordered, the cells morphology and structure were missing, and the AI was significantly increased compared with that in the sham operation group(P<0.01). Meanwhile, compared with the VD model group, the NMFGF1-NPs treatment group showed significant improvement in various behavioral indexes, and the hippocampal neuron cells were intact and orderly, and the AI index was significantly decreased(P<0.01). ELISA and Western blotting analysis showed that compared with that of VD model group and other intervention groups, the content of MDA in the brain of NMFGF1-NPs treatment group was significantly decreased. While the content of SOD, NO and the expressions of Nrf2, SOD-1 and GSTO1/2 was significantly increased (P<0.01). CONCLUSION Nasal administration of NMFGF1-NPs can play the role of antioxidant stress damage by activating Nrf2/ARE signal pathway, and ultimately improve the learning and cognitive function of VD mice.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) is one of the most common inherited mitochondrial diseases. This paper reports a rare mutation associated with MELAS syndrome, the m. 3252 A>G mutation in the MT-TL1 gene encoding the mitochondrial tRNALeu(UUR). The 6-year-old girl suffered from recurrent convulsion and lactic acidemia. The mtDNA sequencing detected a variant m. 3252A>G(MT-TL1 gene) in the proband and her maternal relatives. The heteroplasmic levels in peripheral blood and urine sediment were 66.53% and 97.42%, respectively, which were obviously higher than those of her maternal relatives. Together with 3 previously reported cases, the variant m. 3252A>G could be classified pathogenic. All the reported pathogenic variants in MT-TL1 gene were reviewed to explore the genotype-phenotype correlations of pathogenic variants in MT-TL1 gene.