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: To investigate the effect of orexin-A-mediated regulation of ionotropic glutamate receptors for promoting motor function recovery in rats with spinal cord injury (SCI). METHODS: Thirty-six newborn SD rats (aged 7-14 days) were randomized into 6 groups (n=6), including a normal control group, a sham-operated group, and 4 SCI groups with daily intrathecal injection of saline, DNQX, orexin-A, or orexin-A+DNQX for 3 consecutive days after PCI. Motor function of the rats were evaluated using blood-brain barrier (BBB) score and inclined plane test 1 day before and at 1, 3, and 7 days after SCI. For patch-clamp experiment, spinal cord slices from newborn rats in the control, sham-operated, SCI, and SCI+orexin groups were prepared, and ventral horn neurons were acutely isolated to determine the reversal potential and dynamic indicators of glutamate receptor-mediated currents under glutamate perfusion. RESULTS: At 3 and 7 days after SCI, the orexin-A-treated rats showed significantly higher BBB scores and grip tilt angles than those with other interventions. Compared with those treated with DNQX alone, the rats receiving the combined treatment with orexin and DNQX had significantly higher BBB scores and grip tilt angles on day 7 after PCI. In the patch-clamp experiment, the ventral horn neurons from SCI rat models exhibited obviously higher reversal potential and greater rise slope of glutamate current with shorter decay time than those from sham-operated and orexin-treated rats. CONCLUSIONS Orexin-A promotes motor function recovery in rats after SCI possibly by improving the function of the ionotropic glutamate receptors.
Animals ; Spinal Cord Injuries/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Receptors, Ionotropic Glutamate/metabolism* ; Recovery of Function/drug effects* ; Orexins/pharmacology* ; Male ; Female ; Animals, Newborn ; Neuropeptides/pharmacology* ; Intracellular Signaling Peptides and Proteins/pharmacology*

Objective: To investigate the association between self-rated health status and mortality risk, and to evaluate the predictive value of self-rated health status for mortality risk among the elderly. Methods: Based on the China Health and Retirement Longitudinal Study (CHARLS) database, data of sociodemographic information, self-rated health status and mortality of the elderly aged 60 years and older were collected from 2011 to 2018. The association between self-rated health status and mortality risk among the elderly was analyzed using a multivariable Cox proportional risk regression model. Results: Totally 4 850 individuals were included, with an median age of 65 (interquartile range, 8) years. There were 2 485 males (51.24%) and 2 365 females (48.76%). There were 877 individuals (18.08%) rated their health as good, 2 078 individuals (42.85%) as general, 1 895 individuals (39.07%) as poor. A total of 28 955 person-years were followed up, with an average follow-up of 5.97 years per person. There were 855 deaths by the end of follow-up in 2018, and the median survival time was 7 (interquartile range, 3) years. Multivariable Cox proportional risk regression analysis showed that there were interactive effects of age, sex and self-rated health status on mortality, respectively (both P<0.05). The results of gender-stratified analysis showed that there was no significant association between self-rated health status and mortality risk in old women (P>0.05). The mortality risk was higher in old men with poor self-rated health than with good self-rated health (<70 years, HR=5.382, 95%CI: 3.263-8.876; 70 to 79 years, HR=3.536, 95%CI: 1.070-11.686; ≥80 years, HR=3.043, 95%CI: 1.827-5.066). Conclusion There is an association between self-rated health status and mortality risk among the elderly, the old men with poor self-rated health had a higher mortality risk.

Objective To retrieve,extract,evaluate,and integrate the relevant evidence of postoperative pulmonary rehabilitation management in patients with lung cancer complicated with chronic obstructive pulmonary disease,so as to provide an evidence-based basis for improving the quality of postoperative pulmonary rehabilitation.Methods Relevant literature on postoperative pulmonary rehabilitation of lung cancer complicated with chronic obstructive pulmonary disease were searched by computer from clinical decisions,guideline websites,professional association websites,and comprehensive databases.The types of the literature included clinical decisions,guidelines,expert consensuses,evidence summaries,systematic reviews,meta-analyses,and randomized controlled trials.The retrieval time limit was from the establishment of the database to September 2023.Results A total of 19 articles were included,including 4 clinical decisions,3 guidelines,6 expert consensuses,1 evidence summary,3 systematic reviews,and 2 randomized controlled trials.Through reading,extraction and classification,23 pieces of best evidence were finally formed,including multidisciplinary cooperation,evaluation,pulmonary rehabilitation strategies and health education.Conclusion This study summarizes the best evidence for postoperative lung rehabilitation management in patients with lung cancer and chronic obstructive pulmonary disease.Clinical medical staff can implement practical evidence for postoperative lung rehabilitation based on actual situations,and promote the transformation of evidence-based knowledge into practice.

[Objective]Using CiteSpace software to visualize and analyse the literature related to acupuncture treatment of post-stroke dysphagia in China,to reveal the dynamics of frontiers and the evolution of hotspots in this field,as well as provide suggestions and references for future research.[Methods]By searching the three major Chinese databases,China National Knowledge Internet(CNKI),Wanfang Data and China Science and Technology Journal Database(VIP),the literature related to acupuncture treatment of post-stroke dysphagia was retrieved between the establishment of these databases and June 2023.Then the data issuance,authors,institutions,keywords clustering and keywords emergence were analyzed and presented in a visualization map or chart with CiteSpace 6.1.R6 software.[Results]After searching and screening,a total of 1 585 relevant literatures were included,and the overall trend of the number of studies within the field showed a steady increase in terms of the number of publications.However,links among study authors are scattered and mostly intra-institutional.At the same time,the connection among institutions for cross-regional collaboration is not close enough.Keywords clustering analysis showed that the type of research in the literature mainly consists overviews and clinical randomized controlled trial(RCT).In terms of treatment approaches,the use of combination of multiple therapies is common.The time zone map reflects the continuous process of refinement of acupuncture therapies,from which the creation of a series of new types of acupuncture therapies could be observed.[Conclusion]The field of acupuncture for the treatment of post-stroke dysphagia is becoming increasingly sophisticated.It is predicted that the combination of acupuncture with other common therapies for the treatment of post-stroke dysphagia will remain a hot research topic in the coming years.Meanwhile,there will be a new trend towards integrating resources and conducting high-quality clinical studies with multi-centre collaboration.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.

Nowadays,the one hospital with multiple districts has become a common model for the development of large public hospitals at present.Through the analysis of the common problems in the development of one hospital with multiple districts,the homogeneous management of one hospital with multiple districts has practical problems,it reflected in difficulties in space management,difficulties,difficulties in staff management,difficulties in system management,difficulties in collaborative development of medical service,difficulties in assessment,difficulties in cost management,difficulties in culture integrations.The case of the scientific management of one hospital with multiple districts in a tertiary public hospitals of provincial state-owned is analyzed,the experience are summarized in terms of organizational structure level,development orientation level,personnel level,performance pay level,cost control level,basic facilities level,culture level,to expected to provide references for promoting the construction of one hospital with multiple districts in public hospitals.