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

Objectives:This study aims to explore the impact of new-onset heart conduction block post transcatheter aortic valve replacement(TAVR)on the cardiac conduction status during 1-year follow-up.Methods:A total of 130 patients who completed TAVR surgery at Fuwai Central-China Cardiovascular Hospital from July 2019 to October 2022 were screened.Among them,56 cases with postoperative heart conduction block were selected for analysis.According to the degree of heart block,patients were divided into mild block group(n=36),moderate block group(n=9),and severe block group(n=11).The clinical characteristics and cardiac conduction conditions at 1-year follow-up between different groups were compared.Results:During a mean(8.5±4.1)months follow-up period,10(17.9%)patients had long-term atrioventricular conduction block,and 46(82.1%)patients had partial or complete recovery of heart block,with 28(50.0%)patients with completely recovered cardiac conduction.In the mild block group,22(61.1%)cases were completely recovered,9(25.0%)patients partly recovered,and 5(13.9%)cases uncovered.In the moderate block group,2(22.2%)cases were completely recovered,5(55.6%)patients partly recovered,and 2(22.2%)cases uncovered.Difference in long-term atrioventricular conduction block among three groups was statistically significant(P<0.001).The Kaplan-Meier curve shows that patients with moderate to severe heart block have a higher rate of long-term atrioventricular conduction block(86.1%vs.77.8%vs.72.7%,log-rank P=0.03).Cox multivariate analysis exhibited that old age(≥75 years old,HR=1.204,95%CI:1.051-1.525,P=0.041)and severe heart conduction block(HR=1.106,95%CI:1.100-1.616,P=0.031)are the two independent risk factors for long-term atrioventricular conduction block post TAVR.Conclusions:The ratio of complete cardiac conduction recovery post TAVR is 50.0%.Older age(≥75 year)and new-onset severe heart conduction block are independent risk factors for long-term atrioventricular conduction block post TAVR procedure.

Objective:To investigate the effect of the embryo cryopreservation duration on pregnancy and obstetric outcome.Methods:A retrospective cohort study of 2 662 frozen-thawed embyro tranfer (FET) cycles was conducted in the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital from January 2016 to December 2020. According to embryo cryopreservation duration, the patients were divided into group A (≤1 year, n=2 115), group B (>1 years and ≤3 years, n=319), group C (>3 years and ≤6 years, n=174), and group D (>6 years, n=54). We used the propensity score matching (PSM) to match the baseline data of oocyte retrieval age of the other three groups according to group D at a ratio of 1∶3. Clinical and obstetric outcomes were compared among the four groups. Multiple logistic regression analysis was used to analyze the effect of oocyte retrieval age, embryo transfer age, the duration of embryo cryopreservation, endometrial preparation scheme, endometrial thickness, the number of transferred embryos and the number of high-quality embryos on pregnancy and live birth outcome. Results:1) Before PSM, there were significant differences in the maternal age at oocyte retrieval and embryo transfer and duration of embryo cryopreservation among the four groups(all P<0.001). 2) After PSM, the baseline characteristics of oocyte retrieval age reached a balance among the four groups. There were no statistical differences in the number of embryos transfer, the number of high-quality embryos, the transferred embryo stage, the endometrial regimen among the groups (all P>0.05). The clinical pregnancy rate [37.04% (20/54)] and the live birth rate [33.33% (18/54)] in group D were lower than those in group A [51.57% (82/159), 40.88% (65/159)], group B [50.00% (65/130), 40.77% (53/130)] and group C [49.59% (61/123), 39.02% (48/123)], but the difference was not statistically significant between the four groups ( P=0.310, P=0.781). There were no statistical differences among the four groups in the ratio of male to female newborns, gestational age, birth weight, preterm delivery rate, low birth weight rate, macrosomia rate, birth defects, and premature repture of membranes (all P>0.05). 3) Multiple logistic regression analysis showed that the number of high-quality embryos transferred affected the clinical pregnancy outcome (before PSM, OR=2.614, 95% CI: 2.168-3.151, P<0.001; after PSM, OR=1.984, 95% CI: 1.406-2.800, P<0.001) and live birth (before PSM, OR=2.708, 95% CI: 2.198-3.336, P<0.001; after PSM, OR=2.122, 95% CI: 1.474-3.053, P<0.001). The duration of embryo cryopreservation does not affect the clinical outcome and live birth (all P>0.05). Conclusion:The duration of embryo cryopreservation does not affect the clinical outcome and live birth, but large sample data are still needed to support this conclusion in the future.

Malignant peritoneal mesothelioma (MPM), as a highly aggressive primary malignant tumor of the peritoneum, often leads to structural damage and functional impairment of female reproductive organs during its treatment course. This study presents a clinical case of an MPM patient who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), subsequently achieving successful live birth through in vitro fertilization and embryo transfer. A comprehensive review of relevant literature was conducted to analyze both the potential benefits and associated risks. While the possibility of successful pregnancy exists for MPM patients following combined CRS and HIPEC treatment, significant clinical risks during the gestational process cannot be overlooked. Current evidence remains limited, necessitating more robust clinical data to substantiate these findings.

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 the personnel, equipment, new technology of various radiotherapy units in Gansu Province, aiming to deeply understand the current status of radiotherapy in Gansu Province.Methods:From March 2023 to March 2024, the data of personnel, equipment and technology of different radiotherapy units in Gansu Province were investigated via online questionnaire survey and offline field visits by Gansu Provincial Quality Control Center for Radiation Oncology. The questionable data were reviewed, logical verification and outlier identification were conducted, and all information was entered according to the principle of double entry. Qualitative data were described by frequency (percentage).Results:As of March 2024, there are 26 radiotherapy units in Gansu Province, including 7 units in Lanzhou, capital city of Gansu Province and none in Linxia Hui Autonomous Prefecture and Gannan Tibetan Autonomous Prefecture. The ratio of radiotherapy physicians and physicists was 2.71 vs. 1, lower than the national level of 3.51 vs. 1. Radiotherapy physicians with intermediate and senior titles accounted for 66.2%, 54% for physicists with intermediate and senior titles and 34.0% for therapists with intermediate and senior titles, respectively. There were 1.70 accelerators per million population in Gansu Province. Among 42 accelerators in Gansu Province, 40 were linac and 2 heavy ion accelerators. In Lanzhou, 7 radiotherapy units had 17 linac, and the remaining 11 cities had 23 linac. All 40 linac could perform 3D conformal radiotherapy and intensity-modulated radiotherapy. The high-end equipment could apply advanced technologies such as volumetric modulated arc radiotherapy, stereotactic body radiotherapy, optical surface-guided radiation therapy and adaptive radiation therapy, etc. Relevant data in this survey were improved compared with those in the national surveys conducted in 2006, 2015 and 2019. Conclusions:The radiotherapy status has developed in Gansu Province, whereas uneven development still exists among regions. According to the actual demands of equipment, talents and technology in each region, the structural adjustment should be oriented to the underdeveloped cities and counties in the province to meet the local medical needs.

Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3％dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P＜0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P＜0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P＜0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P＜0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.

Objective:To test the difficulty, discrimination, and reliability of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire.Methods:Two researchers independently translated the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire and cross-checked it to form a Chinese version of the questionnaire. The Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire consists of 24 items, with correct answers scoring one point and incorrect answers scoring zero points, with a total score of 24 points. Convenience sampling was used to select ICU nurses from 14 GradeⅢ Class A hospitals in five provinces/autonomous regions and two municipalities in China for the survey between April and July 2023. The difficulty index, discrimination index, and Cronbach's α coefficient of the questionnaire were analyzed.Results:A total of 1 121 questionnaires were distributed, with 1 020 valid responses, yielding a valid response rate of 90.99%. The mean score of the 1 020 ICU nurses on the Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire was (16.10±5.58) , with a minimum score of 4.00 and a maximum score of 24.00. The Cronbach's α coefficient of the Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire was 0.91. The questionnaire's overall difficulty and discrimination indexes were 0.67 and 0.59, respectively.Conclusions:The Chinese version of the ICU Nurse Pressure Injury Prevention and Care Knowledge Questionnaire has appropriate difficulty, moderate discrimination, and strong reliability, making it a valuable tool for assessing ICU nurses' knowledge of pressure injury-related topics.

Objective:To investigate the effect of the embryo cryopreservation duration on pregnancy and obstetric outcome.Methods:A retrospective cohort study of 2 662 frozen-thawed embyro tranfer (FET) cycles was conducted in the Reproductive Medicine Center, Department of Obstetrics and Gynecology, Tianjin Medical University General Hospital from January 2016 to December 2020. According to embryo cryopreservation duration, the patients were divided into group A (≤1 year, n=2 115), group B (>1 years and ≤3 years, n=319), group C (>3 years and ≤6 years, n=174), and group D (>6 years, n=54). We used the propensity score matching (PSM) to match the baseline data of oocyte retrieval age of the other three groups according to group D at a ratio of 1∶3. Clinical and obstetric outcomes were compared among the four groups. Multiple logistic regression analysis was used to analyze the effect of oocyte retrieval age, embryo transfer age, the duration of embryo cryopreservation, endometrial preparation scheme, endometrial thickness, the number of transferred embryos and the number of high-quality embryos on pregnancy and live birth outcome. Results:1) Before PSM, there were significant differences in the maternal age at oocyte retrieval and embryo transfer and duration of embryo cryopreservation among the four groups(all P<0.001). 2) After PSM, the baseline characteristics of oocyte retrieval age reached a balance among the four groups. There were no statistical differences in the number of embryos transfer, the number of high-quality embryos, the transferred embryo stage, the endometrial regimen among the groups (all P>0.05). The clinical pregnancy rate [37.04% (20/54)] and the live birth rate [33.33% (18/54)] in group D were lower than those in group A [51.57% (82/159), 40.88% (65/159)], group B [50.00% (65/130), 40.77% (53/130)] and group C [49.59% (61/123), 39.02% (48/123)], but the difference was not statistically significant between the four groups ( P=0.310, P=0.781). There were no statistical differences among the four groups in the ratio of male to female newborns, gestational age, birth weight, preterm delivery rate, low birth weight rate, macrosomia rate, birth defects, and premature repture of membranes (all P>0.05). 3) Multiple logistic regression analysis showed that the number of high-quality embryos transferred affected the clinical pregnancy outcome (before PSM, OR=2.614, 95% CI: 2.168-3.151, P<0.001; after PSM, OR=1.984, 95% CI: 1.406-2.800, P<0.001) and live birth (before PSM, OR=2.708, 95% CI: 2.198-3.336, P<0.001; after PSM, OR=2.122, 95% CI: 1.474-3.053, P<0.001). The duration of embryo cryopreservation does not affect the clinical outcome and live birth (all P>0.05). Conclusion:The duration of embryo cryopreservation does not affect the clinical outcome and live birth, but large sample data are still needed to support this conclusion in the future.

Malignant peritoneal mesothelioma (MPM), as a highly aggressive primary malignant tumor of the peritoneum, often leads to structural damage and functional impairment of female reproductive organs during its treatment course. This study presents a clinical case of an MPM patient who underwent cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), subsequently achieving successful live birth through in vitro fertilization and embryo transfer. A comprehensive review of relevant literature was conducted to analyze both the potential benefits and associated risks. While the possibility of successful pregnancy exists for MPM patients following combined CRS and HIPEC treatment, significant clinical risks during the gestational process cannot be overlooked. Current evidence remains limited, necessitating more robust clinical data to substantiate these findings.