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 establish and validate the diagnostic model of ferroptosis genes for acute myocardial infarction (AMI) based on bioinformatics. Methods Five AMI gene expression data were obtained from Gene Expression Omnibus (GEO), namely GSE66360, GSE48060, GSE60993, GSE83500, GSE34198. Among them, GSE66360 was used as the training set to perform differential analysis, and intersection of differential genes and ferroptosis genes was taken to obtain differentially expressed ferroptosis genes in AMI. GO and KEGG enrichment analyses were performed using Metascape website. Subsequently, random forest (RF) algorithm was used to screen out key genes with high classification performance according to the Keeny coefficient score, and artificial neural network (ANN) diagnostic model of AMI ferroptosis feature gene was constructed by model group GSE83500. The area under the receiver operating characteristic curve (AUC) of 10-fold cross-validation was used to evaluate the performance and generalization ability of the model, and 3 external independent datasets were used to verify the diagnostic performance of this model. The single sample gene set enrichment analysis was used to explore the difference in immune cell infiltration between infarcted myocardium and normal myocardium after AMI. In addition, correlation analysis between immune cells and key genes was also conducted. Finally, potential drugs that would prevent and treat AMI by regulating ferroptosis were screened out from the Coremin Medical platform. Results A total of 16 differentially expressed ferroptosis genes were obtained in the training set, GO enrichment analysis showed that they mainly participated in biological functions such as cellular response to biological stimuli and chemical stress, and regulation of interleukin 17. KEGG enrichment analysis showed that these genes were significantly enriched in NOD-like receptor signaling pathway, programmed cell necrosis, Leishmaniasis and other pathways. Four genes with good classification performance were screened out using RF algorithm, namely EPAS1, SLC7A5, FTH1, and ZFP36. The results of 10-fold cross-validation showed that the minimum AUC value was 0.746, the maximum value was 0.906, and the average value was 0.805. The AUC of the ANN model was 0.859, and the AUC values of the three independent validation sets were 0.763 (GSE48060), 0.673 (GSE60993), 0.698 (GSE34198). Immune cell infiltration found that macrophages, mast cells and monocytes were significantly active after AMI. Correlation analysis found that there were positive correlations between 4 key genes and activated dendritic cells, eosinophils and γδT cells. A total of 20 potential western medicines were predicted which could prevent and treat AMI by regulating ferroptosis, and the predicted potential Chinese medicine was mainly heat-clearing and detoxifying and blood-activating and removing blood stasis drugs. Conclusion The identified AMI ferroptosis genes by bioinformatics method have certain diagnostic significance, which provides a reference for disease diagnosis and treatment.

Background Depressive moods among occupational population are prevalent, which seriously affect their mental-physical health and socioeconomic productivity. This has become an urgent public health concern. Objective To understand current situation of depressive mood among an occupational population aged 18 to 60 covering 120 cities of China, and to explore the relationship between work-family conflict and depressive mood as well as the role of life stress in the relationship, as to provide a scientific basis for developing measures to reduce depressive mood in the occupational population. Methods Using the data of the Psychology and Behavior Investigation of Chinese Residents in 2021, an occupational population aged 18 to 60 years was selected as study subjects. A total of 3785 subjects were included in the study. The Work-Family Conflict Scale, Subjective Life Stress Scale, and Patient Health Questionnaire-Depression Scale were used to assess the work-family conflict, life stress, and depressive mood of the subjects. Harman's single-factor method was used to evaluate common method bias in the survey data. One-way ANOVA was applied to test the difference in work-family conflict, life stress, and depressive mood among occupational population by demographic characteristics, and chi-square test was used to analyze the difference in reporting depressive mood. Partial correlation analysis was used to evaluate the correlation between selected variables. Process plug-in was used to test potential mediating effect of life stress on work-family conflict and depressive emotion. Results The scores of work-family conflict, life stress, and depressive mood among the occupational population were 24.60±8.28, 9.28±3.78, and 5.43±5.30, respectively. The prevalence rates of depressive mood was 48.7% (1888/3875). The score of depressive mood among occupational population who never smoked was significantly higher than that of those who smoked (P<0.01). The partial correlation analysis showed that work-family conflict and life stress were positively correlated with depressive mood (r=0.472 and 0.447, P<0.001); work-family conflict was positively correlated with life stress (r=0.361, P<0.001). The mediation analysis results showed that work-family conflict positively associated with life stress (b=0.361, P<0.001); life stress positively associated with depressive mood (b=0.318, P<0.001); work-family conflict positively associated with depressive mood (b=0.357, P<0.001), and played a partial mediating role in the relationship between work-family conflict and depressive mood with an effect size of 0.115 (95%CI: 0.099, 0.130) that accounted for 24.36% of the total effect. Conclusion Work-family conflict may not only directly affect depressive mood among occupational population, but also indirectly affect depressive mood through a mediating effect of life stress.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Environmental Microbiology, as a compulsory foundational course for the major of environmental and ecological engineering. Its knowledge system not only lays a profound theoretical foundation but also evinces a close-knit nexus to practical applications in environmental protection and ecological restoration. This course thus serves as an outstanding platform facilitating both teaching reforms and practical innovations of professional courses. With Environmental Microbiology as a paradigmatic illustration, this paper concentrates on addressing issues like archaic course contents and enervating teaching approaches, with the aspiration of augmenting students' professional acuities, practical dexterities, and innovation and entrepreneurial aptitudes. In light of the aforesaid aim, we initiated an all-encompassing probe into the teaching reform and practicable paradigms from the perspective of amalgamating professional education with innovation-steered stratagems. Across multiple fronts, comprehensive reformative undertakings were implemented, subsuming the optimization and reconfiguration of course contents, the exploration of sundry teaching methodologies, and the scientific erection of an evaluation system. Ultimately, a nascent teaching model dubbed "three-dimensional, six-loop and five-collaborative" was formed. This series of comprehensive and innovative reform measures has not only substantially augmented the profundity and extensiveness of professional knowledge, permeating into the core of disciplinary essence, but also remarkably bolstered students' practical operational capabilities and innovative thinking patterns, thereby catalyzing their transformation into well-rounded individuals with a competitive edge. By virtue of these efforts, a solid foundation has been firmly laid for the teaching reform of Environmental Microbiology and the cultivation of high-caliber environmental professionals in the contemporary era, heralding a new chapter in the development of environmental education.
Environmental Microbiology ; Teaching ; Education, Professional/methods* ; Curriculum

Background Psychological disturbances such as work-family conflict and depressive mood are prevalent among occupational groups and are closely related to eating behavior. Therefore, investigating the influencing factors of eating behavior is of great significance for promoting the health behaviors of occupational populations. Objective To clarify the current situation of eating behavior among the occupational populations aged 18 to 60 years in China, and to explore the relationship between work-family conflict, depressive mood, and eating behavior, and to test the mediating role of depressive mood in the relationship. Methods The study used a data set containing occupational populations aged 18 to 60 years extracted from the 2021 Psychology and Behavior Investigation of Chinese Residents. The Work-Family Conflict Scale, the Chinese version of the Sakata Eating Behavior Scale Short Form, and the Patient Health Questionnaire-Depression Scale were used. Potential influencing factors of eating behavior of the occupational populations were evaluated by multiple linear regression. Structural equation modeling was used to analyze the relationships between work-family conflict, depressive mood, and eating behavior, and the Bootstrap method was used to test the mediating effect of depressive mood on the relationship of work-family conflict and eating behavior. Results Among the occupational populations, the proportion of reporting high work-family conflict was 48.4%, and the proportion of reporting mild depression and above was 48.7%. The total score of eating behavior was (16.16±4.64), and the proportion of high abnormal eating behavior tendency was 39.1%. There were significant differences in eating behavior score among different age, educational level, marital status, number of offspring, occupation, smoking, and drinking groups (P<0.05). The partial correlation analysis showed that work-family conflict and depressive mood were positively correlated with abnormal eating behavior (r=0.367, 0.386, P<0.001); work-family conflict was positively correlated with depressive mood (r=0.466, P<0.001). The results of the multiple linear regression showed that depressive mood, work-family conflict, age, smoking, drinking, and education level were associated with eating behavior (P<0.05). The structural equation modeling indicated that work-family conflict positively associated with depressive mood (b=0.529, P<0.001), depressive mood positively associated with abnormal eating behavior (b=0.292, P<0.001), and work-family conflict positively associated with abnormal eating behavior (b=0.270, P<0.001). Depressive mood played a partial mediating role in the relationship between work-family conflict and eating behavior, and the effect value was 0.154 (95%CI: 0.132, 0.179) that accounted for 36.32% of the total effect. Conclusion Work-family conflict could directly affect the eating behavior among occupational populations, and also indirectly affect eating behavior through a mediating effect of depressive mood. Therefore, optimizing the allocation of tasks between work and family, providing psychological support in need, alleviating work-family conflict and depressive mood may improve the eating behavior and mental health of working populations.

Objective To investigate the predictive value of the expression levels of YY1 transcription fac-tor(YY1)and microRNA(miR)-181a-5p in peripheral blood mononuclear cell for adverse pregnancy out-comes in gestational diabetes mellitus(GDM).Methods A total of 200 patients with GDM were enrolled as the GDM group.100 healthy pregnant women who underwent prenatal examinations during the same period were selected as the control group.The expressions levels of YY1 and miR-181a-5p in peripheral blood mono-nuclear cell were detected by fluorescent quantitative PCR.Receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of YY1 and miR-181a-5p for adverse pregnancy outcomes in GDM pa-tients.Results Compared with the control group,the expression levels of YY1 and miR-181a-5p in peripheral blood mononuclear cell of GDM group were obviously decreased(P＜0.05),and the incidence rates of post-partum hemorrhage,macrosomia and neonatal hypoglycemia in GDM group were obviously higher(P＜0.05).Multivariate Logistic regression analysis showed that age and poor blood glucose control were inde-pendent risk factors for adverse pregnancy outcomes in GDM patients(P＜0.05),and the expression levels of peripheral blood mononuclear cell YY1 and miR-181a-5p were independent protective factors for adverse preg-nancy outcomes in GDM patients(P＜0.05).ROC curve results showed that the area under the curve(AUC)of the expression levels of YY1 and miR-181a-5p in peripheral blood alone and in combination in predicting ad-verse pregnancy outcomes in GDM patients was 0.717,0.751 and 0.832,respectively,and the AUC of their combination was obviously higher than that of the two alone(P＜0.05).Conclusion The decreased expres-sion levels of YY1 and miR-181a-5p in peripheral blood mononuclear cell of GDM patients could increase the risk of adverse pregnancy outcomes,YY1 and miR-181a-5p are closely related to adverse pregnancy outcomes in GDM patients,and both could be used as predictors of adverse pregnancy outcomes in GDM patients.

Objective:To summarize experience of managing adult Langerhans cell histiocytosis(LCH) in hypothalamic-pituitary region(HPR) from Shanghai Huashan Hospital.Methods:Adult HPR-LCH patients diagnosed at oar endocrinology department from January 2013 to February 2022 were included. Clinical characteristics and treatment response were retrospectively analyzed.Results:A total of 27 adult HPR-LCH patients were included, with 14 cases involving the hypothalamus(H group) and 13 cases without(group NH). The common radiological findings included thickening of the pituitary stalk(25/27, 92.6%). At the time of diagnosis, 14 cases(51.9%) presented with panhypopituitarism, and 19 cases(70.4%) exhibited metabolic abnormalities. The group H had higher proportions of adrenal insufficiency, central hypothyroidism, panhypopituitarism, and diabetes compared to group NH(78.6% vs 23.1%; 78.6% vs 23.1%; 92.9% vs 30.8%, 35.7% vs 0%, respectively, all P<0.05). Hypothalamus syndrome was identified in 71.4%(10/14) of group H. The inital diagnosis rate was 79.2%(19/24), with 48.1% and 51.9% through biopsy of sellar and extrasellar lesions, respectively. Repeated biopsies confirmed the diagnosis in 25.9%(7/27) of cases. The peripheral lesions included bone, thyroid, lung, lymph node, thymus and liver. Out of 20 cases treated with chemotherapy, the objective response rate was 85% at 12 weeks. Four cases received local therapy, one case received traditional Chinese medicine treatment, one case abandoned treatment, and one case was lost to follow-up. The median follow-up time was 28(range 15 to 54) months. During this period, there were 3 deaths in group H and 1 death in group NH. Conclusion:Adult HPR-LCH patients presented with diabetes insipidus and high prevalences of hypopituitarism, hypothalamus syndrome and metabolic abnormalities. Typical imaging features were pituitary stalk thickening. A solitary mass in the HPR was usually very small, posing a great challenge for early diagnosis. Systemic evaluation would help to clarify the diagnosis. Patients with hypothalamus involvement had a higher mortality rate, suggesting the hypothalamus as a risk organ with poor prognosis.

Purpose To detect the expression of peroxiso-mal membrane protein 4(PXMP4)in breast cancer tissues and to explore the effect of PXMP4 on the proliferation,invasion,and epithelial-mesenchymal transition(EMT)of breast cancer cells.Methods Bioinformatics and immunohistochemistry(IHC)were used to detect the expression of PXMP4 in breast cancer tissues.In breast cancer cells,Western blot was used to detect the expression of Cyclin D1,E-cadherin,vimentin and N-cadherin after knockdown and overexpression of PMXP4.The proliferation ability of breast cancer cells was analyzed by CCK-8 and plate cloning assay.Scratch healing and Transwell assay an-alyzed the migration and invasion ability of breast cancer cells.Lentivirus was used to construct a PXMP4-silenced MCF-7 cell line,and the PXMP4-silenced MCF-7 cells were injected into the subcutaneous or tail vein of mice to observe lung metastasis and the number of subcutaneous tumors.Results Bioinformat-ics and IHC showed that the expression of PXMP4 in breast cancer tissues was significantly increased(P＜0.05),and the prognosis of breast cancer patients with high expression of PXMP4 was poor(P＜0.05).The clinicopathological analysis showed that the expression of PXMP4 was correlated with tumor grade and lymph node metastasis(P＜0.05).In vitro knock-down of PMXP4 inhibited the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).Conversely,overex-pression of PXMP4 promoted the proliferation,invasion and EMT process of breast cancer cells(P＜0.05).In vivo,the number of lung metastases,the size of subcutaneous tumor,and the expression of Ki67 in tumor tissue were significantly de-creased after silenced PXMP4(P＜0.05).Conclusion PXMP4 is related to tumor grading and lymph node metastasis.PXMP4 promotes proliferation,invasion and EMT process of breast cancer cells.

Objective:To analyze the clinical characteristics and outcomes of patients with invasive fungal sinusitis (invasive fungal rhinosinusitis, IFR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and explored the risk factors for IFR after allo-HSCT.Methods:Nineteen patients with IFR after allo-HSCT at Peking University People’s Hospital from January 2012 to December 2021 were selected as the study group, and 95 patients without IFR after allo-HSCT during this period were randomly selected as the control group (1:5 ratio) .Results:Nineteen patients, including 10 males and 9 females, had IFR after allo-HSCT. The median age was 36 (10–59) years. The median IFR onset time was 68 (9–880) days after allo-HSCT. There were seven patients with acute myeloid leukemia, five with acute lymphoblastic leukemia, two with myelodysplastic syndrome, two with chronic myeloid leukemia, one with acute mixed-cell leukemia, one with multiple myeloma, and one with T-lymphoblastic lymph node tumor. There were 13 confirmed cases and 6 clinically diagnosed cases. The responsible fungus was Mucor in two cases, Rhizopus in four, Aspergillus in four, and Candida in three. Five patients received combined treatment comprising amphotericin B and posaconazole, one patient received combined treatment comprising voriconazole and posaconazole, nine patients received voriconazole, and four patients received amphotericin B. In addition to antifungal treatment, 10 patients underwent surgery. After antifungal treatment and surgery, 15 patients achieved a response, including 13 patients with a complete response and 2 patients with a partial response. Multivariate analysis revealed that neutropenia before transplantation ( P=0.021) , hemorrhagic cystitis after transplantation ( P=0.012) , delayed platelet engraftment ( P=0.008) , and lower transplant mononuclear cell count ( P=0.012) were independent risk factors for IFR after allo-HSCT. The 5-year overall survival rates in the IFR and control groups after transplantation were 29.00%±0.12% and 91.00%±0.03%, respectively ( P<0.01) . Conclusion:Although IFR is rare, it is associated with poor outcomes in patients undergoing allo-HSCT. The combination of antifungal treatment and surgery might be effective.