1.Decoding the immune microenvironment of secondary chronic myelomonocytic leukemia due to diffuse large B-cell lymphoma with CD19 CAR-T failure by single-cell RNA-sequencing.
Xudong LI ; Hong HUANG ; Fang WANG ; Mengjia LI ; Binglei ZHANG ; Jianxiang SHI ; Yuke LIU ; Mengya GAO ; Mingxia SUN ; Haixia CAO ; Danfeng ZHANG ; Na SHEN ; Weijie CAO ; Zhilei BIAN ; Haizhou XING ; Wei LI ; Linping XU ; Shiyu ZUO ; Yongping SONG
Chinese Medical Journal 2025;138(15):1866-1881
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
2.Expert consensus on the prevention and treatment of enamel demineralization in orthodontic treatment.
Lunguo XIA ; Chenchen ZHOU ; Peng MEI ; Zuolin JIN ; Hong HE ; Lin WANG ; Yuxing BAI ; Lili CHEN ; Weiran LI ; Jun WANG ; Min HU ; Jinlin SONG ; Yang CAO ; Yuehua LIU ; Benxiang HOU ; Xi WEI ; Lina NIU ; Haixia LU ; Wensheng MA ; Peijun WANG ; Guirong ZHANG ; Jie GUO ; Zhihua LI ; Haiyan LU ; Liling REN ; Linyu XU ; Xiuping WU ; Yanqin LU ; Jiangtian HU ; Lin YUE ; Xu ZHANG ; Bing FANG
International Journal of Oral Science 2025;17(1):13-13
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
3.Predictive value of the expression levels of YY1 and miR-181a-5p in peripheral blood mononuclear cell for the adverse pregnancy outcomes in gestational diabetes mellitus
Haixia LIU ; Lili WANG ; Xiaomin WEI ; Yuxia YANG ; Zhihui SONG
International Journal of Laboratory Medicine 2024;45(1):12-16
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.
4.Study on the combined detection of mammography,ultrasound Doppler and serum tumor markers in the diagnosis of early breast cancer
Haixia WANG ; Qian SONG ; Guohong ZHENG ; Gang CAO
China Medical Equipment 2024;21(1):82-87
Objective:To explore the values of single and combined detection of mammography,ultrasound Doppler and serum markers of tumor included serum prostate specific antigen(PSA),serum carbohydrate antigen 15-3(CA153),mucin 1(MUC1)and human growth differentiation factor 3(GDF3)in diagnosing early breast cancer.Methods:A total of 96 patients with breast cancer,who admitted to Tangshan People's Hospital from January 2018 to December 2021 and were confirmed by pathological examination,were selected as breast cancer group.At the same time,70 patients with benign breast diseases who received diagnosis and treatment in our hospital were selected as benign lesions group.In addition,50 normal people who were confirmed as health by physical examination in our hospital were selected as research subjects of healthy control group.The postoperative pathological examination was used as the gold standard to compare the diagnostic values of single mammography,ultrasonic Doppler examination,serum PSA,CA153,MUC1,GDF3 and the combined examination of them for breast cancer.Results:In the breast cancer group,78 cases of the 96 patients with breast cancer were diagnosed as malignant tumor by ultrasound on breast,with a positive detection rate of 81.3%,and 80 cases of them were diagnosed as malignant tumor by mammography X-ray examination,with a positive detection rate of 83.1%.The levels of serum PSA,CA153,MUC1 and GDF3 of breast cancer group were respectively higher than those of the benign lesion group and healthy control group,and the differences were statistically significant(t=8.783,10.361,11.258,18.965,9.564,12.658,12.688,20.163,P<0.05).Using breast cancer as the dependent variable,and using serum PSA,CA153,MUC1 and GDF3 as independent variable to perform Logistic regression analysis.The results of Logistic regression analysis indicated that serum PSA,CA153,MUC1 and GDF3 were important risk factors of breast cancer(OR value =1.165,1.168,1.472,1.248,P<0.05).The results of receiver operating characteristic(ROC)curve(95%CI),sensitivity and specificity of single application of each indicator of ultrasound on breast,mammography,serum PSA,CA153,MUC1 and GDF3 were respectively[0.723(0.595-0.851),82.56%and 67.32%],[0.761(0.636-0.886),85.79%and 65.36%],[0.833(0.726-0.941),81.48%and 85.73%],[0.837(0.738-0.926),61.25%and 70.17%],[0.768(0.648-0.889),71.49%and 80.87%],[0.613(0.469-0.758),52.94%and 50.57%].However,the AUC(95%CI),sensitivity and specificity of the combined application of 6 items were respectively 0.958(0.905-0.999),96.37%and 84.83%,which had higher diagnostic efficiency.Conclusion:The combined detection performance of mammography,ultrasound Doppler and serum PSA,CA153,MUC1 and GDF3 is higher than that of single each detection,which is helpful to conduct early identification and diagnosis for breast cancer.
5.A case of acute pulmonary edema caused by exertional heat stroke
Lingli SONG ; Haixia WANG ; Wei FANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(10):769-771
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.
6.A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children
Li SONG ; Ling JIN ; Yonghong ZHANG ; Xiaomei YANG ; Yanlong DUAN ; Mincui ZHENG ; Xiaowen ZHAI ; Ying LIU ; Wei LIU ; Ansheng LIU ; Xiaojun YUAN ; Yunpeng DAI ; Leping ZHANG ; Jian WANG ; Lirong SUN ; Rong LIU ; Baoxi ZHANG ; Lian JIANG ; Huixia WEI ; Kailan CHEN ; Runming JIN ; Xige WANG ; Haixia ZHOU ; Hongmei WANG ; Shushuan ZHUANG ; Chunju ZHOU ; Zifen GAO ; Xiao MU ; Kaihui ZHANG ; Fu LI
Chinese Journal of Pediatrics 2024;62(10):941-948
Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.
7.Progress on structural abnormalities in the cerebral cortex in children with attention deficit/hyperactivity disorder
Haixia YUAN ; Xinmin HAN ; Tianyi CHEN ; Yuchen SONG
The Journal of Practical Medicine 2024;40(10):1455-1459
Neuroimaging is increasingly widely used in the field of ADHD research,and more and more studies have shown that ADHD patients have structural abnormalities such as reduced cortical volume,thinning thickness,and reduced surface area,which are related to complex clinical symptoms and abnormal brain function in patients.However,the use of neuroimaging to identify biomarkers as an objective diagnostic tool for ADHD still faces many challenges.Multimodal studies can be used to explore the relationship between the structure and function of different brain regions in ADHD patients,and to use neuroimaging to reveal the mechanism of the evolution of clinical symptoms in the whole life cycle of ADHD patients.
8.Analysis of pollen sensitization characteristics of artemisia allergic rhinitis in three urban and rural areas of Inner Mongolia
Chunying LI ; Xiaojia LIU ; Haixia XU ; Qiang FU ; Dongyue XU ; Xiaobo CUI ; Ji LIU ; Bolong SONG ; Ming ZHENG ; Yuhui OUYANG ; Xiangdong WANG ; Xiaoling LIU
Chinese Journal of Preventive Medicine 2024;58(6):806-814
Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.
9.A case of acute pulmonary edema caused by exertional heat stroke
Lingli SONG ; Haixia WANG ; Wei FANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(10):769-771
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.
10.Analysis of pollen sensitization characteristics of artemisia allergic rhinitis in three urban and rural areas of Inner Mongolia
Chunying LI ; Xiaojia LIU ; Haixia XU ; Qiang FU ; Dongyue XU ; Xiaobo CUI ; Ji LIU ; Bolong SONG ; Ming ZHENG ; Yuhui OUYANG ; Xiangdong WANG ; Xiaoling LIU
Chinese Journal of Preventive Medicine 2024;58(6):806-814
Objective:To investigate the distribution rules of artemisia pollen and the clinical sensitization characteristics of allergic rhinitis (AR) induced by artemisia pollen in three urban and rural areas of Inner Mongolia.Methods:From March to October 2019, in 3 central cities (Chifeng, Hohhot, Ordos) and rural areas of Inner Mongolia, an epidemiological investigation method combining multi-stage stratified random sampling and face-to-face questionnaire survey was adopted to screen suspected AR patients, and skin prick test (SPT) was applied for diagnosis. At the same time, pollen monitoring was carried out in 3 areas to analyze the distribution and clinical sensitization characteristics of artemisia pollen.SPSS26.0 statistical software was used to process all the data. Chi-square test was used to compare rates among different age, sex, region and nationality, Spearman test was used to describe correlation analysis, and pairwise comparison of positive rates among multiple samples was used Bonferroni method.Results:Among the 6 393 subjects, 1 093 cases were diagnosed with AR, and the prevalence of AR was 17.10% (1 093/6 393). Among them, pollen-induced allergic rhinitis, the prevalence of PiAR was 10.97% (701/6 393), accounting for 64.14%(701/1 093).The highest incidence was in the youth group (20-39 years old), accounting for 46.94% (329/701).The diagnosed prevalence was higher in females than in males (11.35% vs. 10.64%, χ2 value 12.304, P<0.001).The prevalence rate of ethnic minority was higher than that of Han nationality (13.01% vs. 10.65%, χ2 value 6.296, P=0.008).The prevalence in urban areas was also significantly higher than that in rural areas (18.40% vs. 5.50%, χ2 value 10.497, P<0.001).There was significant difference in prevalence rate among the three regions in Inner Mongolia (6.06% in Chifeng, 13.46% in Hohhot, 16.39% in Ordos, χ2 value 70.054, P<0.001).The main clinical symptoms of artemisia PiAR were sneezing (95.58%), nasal congestion (91.73%) and nasal itching (89.30%).Allergic conjunctivitis accounted for 79.60% (558/701), chronic sinusitis for 55.63% (390/701), asthma for 23.25% (163/701).The pattern of artemisia pollen sensitization was mainly multiple sensitization, and the frequency of clinical symptoms and clinical diseases induced by hypersensitization with other allergens accounted for more than that caused by single artemisia pollen. The spread period of Artemisia pollen in the three regions was from June to October, and the peak state was in August in summer. The peak time of clinical symptoms in artemisia PiAR patients was about 2 weeks earlier than the peak time of pollen concentration, and the two were significantly positively correlated ( R=0.7671, P<0.001). Conclusion:Artemisia pollens are the dominant pollens in late summer and early autumn in Inner Mongolia, and the prevalence of artemisia PiAR is high. Controlling the spread of Artemisia pollens is of great significance for the prevention and treatment of AR.

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