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 investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Objective Taking a tertiary hospital in Beijing as an example,to investigate patients'continuous use inclination towards utilizing Internet diagnosis and treatment,dissect the influential factors and elucidate the pathway through which these factors exert their impact,and propose recommendations for optimizing internet diagnosis and treatment services in the hospital.Methods Based on the model of continuous use of information system and the model of success of information system,it constructed a structural equation model of the willingness to use Internet diagnosis and treatment service continuously and put forward the hypotheses,conducted a questionnaire survey.Descriptive analysis,reliability and validity tests,structural model analysis and hypothesis testing were conducted using Excel and SmartPLS 4.0 software to validate the research hypotheses.Results The information quality,service quality,and system quality of Internet diagnosis and treatment services have a positive effect on patients'willingness to continue to use them,with perceived usefulness and user satisfaction playing a major mediating role.Conclusion Internet hospitals should establish skill training and medical record review mechanisms,improve service processes and communication norms,optimize system design and user experience,enhance interactivity and personalized services,to promote the sustainable development of Internet diagnosis and treatment services in entity medical institutions.

Objective To observe the value of intratumoral and peritumoral CT radiomics for predicting Ki-67 expression level of lung adenocarcinoma with mixed ground glass nodules.Methods Totally 284 cases of pathologically confirmed lung adenocarcinoma with mixed ground glass nodules were retrospectively enrolled,among them 197 cases were taken as training set(54 cases with high and 143 cases with low Ki-67 expression)and 87 cases as validation set(27 cases with high and 60 cases with low Ki-67 expression).Intratumoral and peritumoral radiomic features were obtained from non-contrast chest CT,and radiomic models for predicting Ki-67 expression in lung adenocarcinoma with mixed ground glass nodules were established using adaptive boosting,light gradient boosting machine(LightGBM)and multilayer perceptron algorithms based on intratumoral features,peritumoral features,as well as intratumoral+peritumoral features,respectively,and the optimal radiomics signature was selected according to the area under the receiver operating characteristic curve(AUC).Univariate and multivariate logistic regression analysis were performed to identify independent impact factors of Ki-67 expression level,and a clinical model was constructed,and the efficacy of the models were evaluated.Results Among radiomics models,LightGBMintratumoral+peritumoral model had the highest AUC(0.934 in training set and 0.845 in validation set),which were superior to that of clinical model(0.616 in training set and 0.684 in validation set)(both P＜0.05)Conclusion Intratumoral and peritumoral CT radiomics had good efficacy for predicting Ki-67 expression level of lung adenocarcinoma with mixed ground glass nodules.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective To observe the value of intratumoral and peritumoral CT radiomics for predicting Ki-67 expression level of lung adenocarcinoma with mixed ground glass nodules.Methods Totally 284 cases of pathologically confirmed lung adenocarcinoma with mixed ground glass nodules were retrospectively enrolled,among them 197 cases were taken as training set(54 cases with high and 143 cases with low Ki-67 expression)and 87 cases as validation set(27 cases with high and 60 cases with low Ki-67 expression).Intratumoral and peritumoral radiomic features were obtained from non-contrast chest CT,and radiomic models for predicting Ki-67 expression in lung adenocarcinoma with mixed ground glass nodules were established using adaptive boosting,light gradient boosting machine(LightGBM)and multilayer perceptron algorithms based on intratumoral features,peritumoral features,as well as intratumoral+peritumoral features,respectively,and the optimal radiomics signature was selected according to the area under the receiver operating characteristic curve(AUC).Univariate and multivariate logistic regression analysis were performed to identify independent impact factors of Ki-67 expression level,and a clinical model was constructed,and the efficacy of the models were evaluated.Results Among radiomics models,LightGBMintratumoral+peritumoral model had the highest AUC(0.934 in training set and 0.845 in validation set),which were superior to that of clinical model(0.616 in training set and 0.684 in validation set)(both P＜0.05)Conclusion Intratumoral and peritumoral CT radiomics had good efficacy for predicting Ki-67 expression level of lung adenocarcinoma with mixed ground glass nodules.

BACKGROUND:Unilateral chronic ankle instability has adverse effects on the affected limb,and evidence has shown that the nonaffected side may be similarly involved,but direct evidence is currently lacking.OBJECTIVE:To investigate the effects of unilateral chronic ankle instability on bilateral postural stability,proprioception,plantar tactile sensation,and muscle strength.METHODS:A total of 122 participants were recruited in this study,including 67 individuals with unilateral chronic ankle instability and 55 individuals without chronic ankle instability.Postural stability,proprioception,plantar tactile sensation and muscle strength were tested bilaterally in individuals with unilateral chronic ankle instability,as well as in those without chronic ankle instability.One-way analysis of variance or Kruskal-Wallis test was used for intergroup comparisons.RESULTS AND CONCLUSION:(1)Compared with individuals without chronic ankle instability,individuals with chronic ankle instability had longer time to stability in the anterior-posterior direction bilaterally(P=0.001-0.012),and longer time to stability in the medial-lateral direction on the affected side(P=0.012-0.025);had higher proprioception thresholds of plantarflexion,dorsiflexion,inversion,and eversion of the bilateral ankles(P=0.000-0.035);showed lower tactile sensation sensitivities of the bilateral great toe,first metatarsal head,fifth metatarsal head,arch,and heel(P=0.000-0.008);and had weaker muscle strength for inversion and eversion of the bilateral ankles(P=0.000-0.019).(2)Individuals with unilateral chronic ankle instability have bilateral deficits in postural stability,proprioception,plantar tactile sensation,and muscle strength.Therefore,the rehabilitation needs of both limbs should be fully considered when treating chronic ankle instability.

BACKGROUND:Unilateral chronic ankle instability has adverse effects on the affected limb,and evidence has shown that the nonaffected side may be similarly involved,but direct evidence is currently lacking.OBJECTIVE:To investigate the effects of unilateral chronic ankle instability on bilateral postural stability,proprioception,plantar tactile sensation,and muscle strength.METHODS:A total of 122 participants were recruited in this study,including 67 individuals with unilateral chronic ankle instability and 55 individuals without chronic ankle instability.Postural stability,proprioception,plantar tactile sensation and muscle strength were tested bilaterally in individuals with unilateral chronic ankle instability,as well as in those without chronic ankle instability.One-way analysis of variance or Kruskal-Wallis test was used for intergroup comparisons.RESULTS AND CONCLUSION:(1)Compared with individuals without chronic ankle instability,individuals with chronic ankle instability had longer time to stability in the anterior-posterior direction bilaterally(P=0.001-0.012),and longer time to stability in the medial-lateral direction on the affected side(P=0.012-0.025);had higher proprioception thresholds of plantarflexion,dorsiflexion,inversion,and eversion of the bilateral ankles(P=0.000-0.035);showed lower tactile sensation sensitivities of the bilateral great toe,first metatarsal head,fifth metatarsal head,arch,and heel(P=0.000-0.008);and had weaker muscle strength for inversion and eversion of the bilateral ankles(P=0.000-0.019).(2)Individuals with unilateral chronic ankle instability have bilateral deficits in postural stability,proprioception,plantar tactile sensation,and muscle strength.Therefore,the rehabilitation needs of both limbs should be fully considered when treating chronic ankle instability.

Objective Taking a tertiary hospital in Beijing as an example,to investigate patients'continuous use inclination towards utilizing Internet diagnosis and treatment,dissect the influential factors and elucidate the pathway through which these factors exert their impact,and propose recommendations for optimizing internet diagnosis and treatment services in the hospital.Methods Based on the model of continuous use of information system and the model of success of information system,it constructed a structural equation model of the willingness to use Internet diagnosis and treatment service continuously and put forward the hypotheses,conducted a questionnaire survey.Descriptive analysis,reliability and validity tests,structural model analysis and hypothesis testing were conducted using Excel and SmartPLS 4.0 software to validate the research hypotheses.Results The information quality,service quality,and system quality of Internet diagnosis and treatment services have a positive effect on patients'willingness to continue to use them,with perceived usefulness and user satisfaction playing a major mediating role.Conclusion Internet hospitals should establish skill training and medical record review mechanisms,improve service processes and communication norms,optimize system design and user experience,enhance interactivity and personalized services,to promote the sustainable development of Internet diagnosis and treatment services in entity medical institutions.

Objective:To investigate the value of left ventricular systolic synchrony assessed by gated myocardial perfusion imaging(GMPI)in predicting major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease(CHD).Methods:In this retrospective study, clinical data from elderly patients who had completed a two-day assessment of resting-loading GMPI between September 2012 and February 2014 in Beijing Hospital were collected, including the summed stress score(SSS)for total ischemic burden, measured by GMPI, left ventricular ejection fraction(LVEF), peak filling rate(PFR), phase band width(PBW), phase standard deviation(PSD)and phase entropy(PE).Follow-up of MACE was conducted.Independent risk factors for MACE were analyzed using a multifactorial Cox proportional hazards regression model, and the cumulative MACE incidence was analyzed using the Kaplan-Meier survival curve.Results:A total of 427 subjects were enrolled, including 200(46.8%)men, with a mean age of 74.1±6.5(60-92)years and 323(75.6%)aged ≥ 70 years.The median follow-up time was 54.7 months.At the end of follow-up, MACE occurred in 47 patients(11.0%).Compared with the group without MACE, the incidences of hypertension, hyperlipidemia, and hyperuricemia were significantly higher( χ2=5.20, 5.62, 3.86, all P<0.05), LVEF and PFR were significantly lower( t=-5.51, -5.23, both P<0.001), and SSS, PSD, PBW, and PE were significantly higher( Z=4.78, t=5.14, 5.78, 5.62, all P<0.001)in the MACE group.The results of Cox proportional hazards regression model analysis suggested that age ≥ 70(hazard ratio: 2.57, 95% CI: 1.08-6.13), abnormal perfusion(hazard ratio: 2.60, 95% CI: 1.31-5.15), increased PSD(hazard ratio: 3.72, 95% CI: 1.72-8.05)and increased PE(hazard ratio: 4.09, 95% CI: 1.94-8.63)were independent risk factors for the occurrence of MACE(all P<0.05).Further analysis on 323 patients ≥ 70 years indicated that abnormal perfusion(hazard ratio: 2.96, 95% CI: 1.40-6.26), increased PSD(hazard ratio: 3.51, 95% CI: 1.56-7.89), and increased PE(hazard ratio: 4.49, 95% CI: 2.08-9.71)were independent risk factors for MACE( P<0.05 for all). Conclusions:Parameters of GMPI systolic synchrony analysis can very well identify the population at high risk of MACE in elderly patients with CHD.