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

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

Objective To investigate necroptosis-related diagnostic biomarkers of bronchopulmo-nary dysplasia(BPD)and their relationships with the immune microenvironment through the analysis of necroptosis-related genes(NRGs)in BPD.Methods The dataset GSE32472 was downloaded from the Gene Expression Omnibus(GEO)database,and NRGs were obtained from the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway and Gene Cards databases.Differentially expressed necroptosis-related genes(DE-NRGs)were screened,and their biological functions and pathways were explored through functional enrichment analysis.Machine learning algorithms,inclu-ding least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE),were applied to screen feature genes.The Cell-type Ⅰdentification By Estimating Relative Subsets of RNA Transcripts(CIBERSORT)algorithm and the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues using Expression Data(ESTIMATE)algo-rithm were used to explore the immune infiltration characteristics of BPD.Spearman correlation anal-ysis between feature genes and immune cells was performed using the"corrplot"package in R lan-guage.Results A total of 19 DE-NRGs were identified.The main biological functions and path-ways of DE-NRGs included the regulation of necroptosis and inflammatory responses.Three feature genes,namely flotillin-2(FLOT2),CASP8 and FADD-like apoptosis regulators(CFLAR),and charged multivesicular body protein 7(CHMP7),were further screened to construct a nomogram.In the validation sets GSE8586 and GSE188944,the area under the curve(AUC)values were all greater than 0.7.CIBERSORT analysis revealed that BPD group presented a higher proportion of naive B cells,neutrophils,eosinophils and resting mast cells compared to control group(P＜0.05).Meanwhile,the proportion of CD8+T cells,CD4+naive T cells,CD4+resting memory T cells,regulatory T cells,resting natural killer(NK)cells,M0 macrophages,M2 macrophages and activated dendritic cells was lower than that in the control group(P＜0.05).ESTIMATE analysis showed that the stromal score in the BPD group was higher than that in the control group,while the immune score was lower,with statistically significant differences(P＜0.05).Correlation analysis between the three feature genes and ESTIMATE scores indicated that FLOT2 and CFLAR were posi-tively correlated with the stromal score and negatively correlated with the immune score,whereas CHMP7 was positively correlated with the immune score and negatively correlated with the stromal score.Conclusion The three necroptosis-related feature genes can serve as diagnostic biomarkers for BPD-related necroptosis,with high diagnostic efficacy.They may play an important roles through immune mechanisms,providing new insights and theoretical references for the early diagnosis and immune intervention of BPD.

[摘 要] 目的：研究芳香烃受体（AHR）在乳腺癌中的表达及其对乳腺癌细胞增殖、凋亡和药物敏感性的调控机制。方法：通过GEPIA数据库数据分析乳腺癌组织及癌旁组织中AHR的表达水平，探讨其与患者生存期的关联。利用基因敲低和过表达技术构建AHR表达变化的乳腺癌细胞，采用CCK-8实验、细胞计数和流式细胞分析等方法评估AHR对细胞增殖、凋亡和药物敏感性的影响，通过免疫印迹法验证相关分子机制。此外，利用AHR激动剂6-甲酰基吲哚并[3,2-B]咔唑（FICZ）研究外源性激活AHR对乳腺癌细胞多柔比星（DOX）敏感性的影响。结果：GEPIA数据库数据分析结果显示，乳腺癌组织中AHR呈明显低表达（P < 0.05）；对155例乳腺癌患者的生存期进行统计分析也显示AHR低表达与不良预后呈正相关（P < 0.05）。敲低AHR促进细胞增殖（P < 0.05），过表达则能抑制其增殖（P < 0.05）并促进其凋亡（P < 0.05）。外源激活AHR能增强乳腺癌细胞对DOX的敏感性（P < 0.05）。AHR可与MYC基因启动子结合，抑制MYC表达（P < 0.05），从而影响乳腺癌的进展。结论：AHR在乳腺癌中通过调控MYC表达影响细胞增殖和凋亡，外源激活AHR可能成为提高乳腺癌细胞对DOX敏感性的治疗策略。

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To explore the characteristics of gray matter volume (GMV) and structural covariant network (SCN) in patients with cerebral small vessel disease (CSVD) related cognitive impairment.Methods:This was a cross-sectional study. Ninety-eight patients with CSVD who attended Wuxi People′s Hospital of Nanjing Medical University between October 2021 and December 2022 were prospectively included. The patients were evaluated using the cognitive status assessment scale and were categorized into 57 cases in the CSVD with cognitive impairment group and 41 cases in the CSVD without cognitive impairment group according to the presence or absence of cognitive impairment. 3D-T 1WI structural image data were collected, and GMV differences between the two groups were compared by SPM 12 toolbox and CAT12 toolkit. At the same time, Pearson correlation analysis was also performed to analyze the GMV of differences between the 2 groups and cognitive status assessment scale scores. The BCT software package based on MATLAB platform was used to construct the GMV-related structural covariant network (SCN), and the graph theory method was utilized for SCN analysis to calculate the area under the curve (AUC) of the global and local parameters within the set sparsity range, and the permutation test was used to compare the differences in the AUC of the 2 groups. Results:In the CSVD with cognitive impairment group, GMV in bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala was significantly lower than that in the CSVD without cognitive impairment group (family wise error corrected P<0.05), and the GMV in these regions had correlation with cognitive status assessment scale ( P<0.05). At the global network level of the SCN, the area under the curve (AUC) of the characteristic path length was significantly higher in the CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.023), while the AUC of global efficiency was significantly lower in CSVD with cognitive impairment group than in the CSVD without cognitive impairment group ( P=0.005). At the local level, the nodal degree and nodal efficiency of the left putamen were significantly decreased in the CSVD with cognitive impairment group compared to the CSVD without cognitive impairment group (false discovery rate corrected P<0.05). Conclusions:GMV reduce in patients of CSVD with cognitive impairment in the bilateral hippocampus, parahippocampal gyrus, fusiform gyrus, and left amygdala. In the structural covariance network, characteristic path length increase while global efficiency reduce, and node degree and nodal efficiency of the left putamen reduce.

Objective:To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC.Results:After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance ( P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% ( P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% ( P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival ( HR=0.58, 95% CI: 0.40-0.86) and overall survival ( HR=0.53, 95% CI: 0.35-0.79). Conclusion:These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Objective To explore the effectiveness of high-definition diffusion weighted imaging(DWI)sequence combined with T1 WI-fat suppression(FS)dynamic contrast enhancement(DCE)sequence for preoperative T-stage of rectal cancer by using 3.0T MRI standardized scanning.Methods A retrospective analysis was conducted on MRI images of 57 patients with rectal cancer confirmed by pathology.Before surgery,the patients underwent 3.0T MRI standardized rectal cancer scan methods,including routine sequence,high-definition DWI sequence,and T1 WI-FS DCE sequence,etc.Then two experienced physicians evaluated the T-stage of preoperative rectal cancer through high-definition DWI(transverse and sagittal sections)and T1 WI-FS DCE sequences in the double-blind method.Using the postoperative pathological results of rectal cancer as the"gold standard",two sequences were combined to evaluate the accuracy,sensitivity,and specificity of rectal cancer T-stage.Results Among the 57 cases,there were 9 cases of upper rectal cancer,39 cases of middle rectal cancer,and 9 cases of lower rectal cancer.The accuracy rates of preoperative T-stage diagnosis for rectal cancer by two evaluator were both 85.7％(6/7)in T1 stage,88.2％(15/17)and 94.1％(16/17)in T2 stage,96.9％(31/32)and 93.8％(30/32)in T3 stage,and both 100.0％(1/1)in T4 stage.For evaluator 1,the sensitivity and specificity of the rectal cancer T-stage diagnosis were 96.1％and 83.3％,and for evaluator 2 were 94.1％and 83.3％,respectively.For rectal cancer MRI diagnosis,the accuracy rates and sensitivity were higher when combining the high-definition DWI sequence and T1 WI-FS DCE sequence,compared with a single high-definition DWI sequence or T1 WI-FS DCE sequence,and the difference was statistically significant.The average preoperative apparent diffusion coefficient(ADC)value of rectal cancer was compared between the corresponding postoperative pathological T1 to T4 stage groups,and the difference was statistically significant.Conclusion The combination of high-definition DWI sequence and T1 WI-FS DCE sequence improves the accuracy of rectal cancer T-stage,providing assistance for personalized clinical treatment.

Objective To explore the changes of resting-state degree centrality(DC)in elderly patients with chronic insomnia disorder(CID).Methods Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected from 26 untreated elderly patients with CID(CID group)and 45 healthy controls(HC)(HC group).Two-sample t-test was conducted to compare the intergroup differences in whole-brain DC values,and the correlation between DC values in different brain regions and clinical indicators were analyzed,and logistic regression analysis was performed to verify the diagnostic efficacy of changes in DC values for elderly CID.Results Compared with the HC group,the DC values of the right insula,left rolandic operculum,and opercular part of right inferior frontal gyrus in the elderly CID group decreased[P＜0.05,false discovery rate(FDR)corrected],while the DC values of the right middle frontal gyrus increased(P＜0.05,FDR corrected).And the DC values of the opercular part of right inferior frontal gyrus in the elderly CID group were positively correlated with sleep efficiency(r=0.504,P=0.009)and self-rating depression scale(SDS)(r=0.401,P=0.042),respectively.The sensitivity of DC value in the opercular part of right inferior frontal gyrus for diagnosing elderly CID was 0.822,the specificity was 0.615,and the accuracy was 0.701.Conclusion Elderly CID patients have abnormal DC values in the right insula,left rolandic operculum,opercular part of right inferior frontal gyrus and right middle frontal gyrus,which may provide imaging evidence for exploring the pathogenesis of CID and clinical diagnosis and treatment.

This paper reports a case of acute pulmonary edema caused by exertional heat stroke due to imbalance of body heat production and heat dissipation caused by high intensity military training physical activities. The patient's lesions developed rapidly and pulmonary edema progressed rapidly and diffusingly. After early identification, active invasive mechanical ventilation and hormone therapy, the pulmonary imaging lesions of pulmonary edema were rapidly absorbed, and the dyspnea was improved. This article discusses the incidence, imaging features and treatment of acute pulmonary edema caused by exertional heat stroke, and provides reference for clinical diagnosis and treatment.