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 explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability. Methods: From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated. Results: The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2. Conclusions Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.

[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.

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: 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 evaluate the incidence and case fatality rate of cardiovascular disease (CVD) among populations in urban and rural communities in eastern, central and western regions of China.Methods:The present study was based on the data of the Prospective Urban and Rural Epidemiology (PURE)-China cohort, which enrolled participants who had at least one follow-up visit and complete information on age and sex. Information on baseline demographics, cardiovascular risk factors, and prevention and treatment for CVD were collected. CVD and mortality events were documented using the standardized case report form of the PURE Global Study to assess the incidence and case fatality rate of CVD among populations in urban and rural communities in eastern, central and western China.Results:This study included a total of 47 262 community-dwelling participants (age: (51.1±9.6) years; female, n=27 529, 58.2%) from 115 urban and rural communities in 12 provinces across the eastern, central, and western regions of China. Over a follow-up period of 11.9 (9.5, 12.6) years, 2 686 deaths and 5 873 cardiovascular events were documented. The incidence of CVD was 11.90 (95%CI: 11.60-12.21)/1 000 person-years. A significant difference in CVD incidence was observed across regions ( Ptrend<0.001), which was highest in the western provinces (13.99 (95% CI: 13.33-14.65)/1 000 person-years), intermediate in the eastern provinces (11.92 (95% CI: 11.52-12.33)/1 000 person-years), and lowest in the central provinces (8.87 (95% CI: 8.25-9.50)/1 000 person-years). The 1-year case fatality rate of CVD demonstrated an increasing trend from eastern to western regions (eastern: 10.20% (95% CI: 6.95-14.73); central: 13.50% (95% CI: 9.90-18.14); western: 18.62% (95% CI: 14.95-22.94); Ptrend<0.001). Moreover, the incidence of major CVD was consistently higher in rural areas compared with urban areas across eastern ( P<0.001), central ( P=0.01) and western ( P<0.001)_regions, respectively. The 1-year case fatality rate in rural areas was also significantly higher compared with that in urban areas in both eastern ( P<0.001) and western regions ( P=0.02). Conclusions:The incidence and case fatality rate of CVD were high among middle-aged population in China, especially those in western regions with low socioeconomic levels and in rural areas.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective:Exploration on the mechanism of acupuncture-targeted therapy for rheumatoid arthritis and identification of candidate Chinese materia medica.Methods:Targets of acupuncture for RA were collected from related literature, and GSE205962 gene chips were obtained from GEO database. The weighted co-expression network (WGCNA) was constructed by screening differentially expressed genes using R 4.3.1. The collection targets were taken to intersect with the differential genes, and the common genes were obtained for high-throughput GO and KEGG enrichment. The Hub genes were screened by constructing protein interaction networks using the String database and Cytoscape 3.9.0 software. The CIBERSORT algorithm was used to explore the mechanisms of RA immune infiltration, and finally the Coremine Medical database was applied to predict Chinese materia medica.Results:A total of 8 key targets were selected (RHOA, JAK1, FYN, LCK, STAT1, STAT3, EGF, GATA3). The results of immune infiltration analysis showed that various immune cells were closely related to the biological processes of rheumatoid arthritis, including γδ T cells, monocytes, regulatory T cells, CD8 T cells, etc. Saposheikovize Radix, Cinnamomi Ramulus, Anemarrhenae Rhizoma, Dendrobii Caulis, Rehmannine Radix, Lonicerae Japonicae Flos, Pinelliae Rhizoma, Cimicifugae Rhizoma, Poria, Stephaniae Tetrandrae Radix were the 10 kinds of commonly used key Chinese materia medica in the treatment of RA.Conclusions:Acupuncture and moxibustion may treat RA by regulating RHOA, JAK1, FYN, LCK and other core targets. This study predicts that Chinese materia medica can be used as a source of drugs for the treatment of RA, and can provide new ideas for the combination of acupuncture and medicine for the treatment of RA.

Objective To identify the relationship between physical activity,insulin resistance and cardiovascular risk in individuals with different glucose tolerance status and to provide evidence for exercise intervention in people with different glucose tolerance status.Methods A total of 691 patients with different glucose metabolism status were recruited as subjects of the research.Spearman correlation analysis was used to study the relationship between exercise frequency and insulin resistance,insulin sensitivity,neck circumference(NC)and neck circumference height ratio(NHtR)in the subjects with different glucose metabolism status,the relationship between NC and insu-lin resistance and insulin sensitivity in different glucose metabolism groups.Results 171(62.9%)Subjects with diabetes were intervened by exercised every day.Spearman correlation analysis showed the correlation between exer-cise frequency and tri-glyceride triglyceride-glucose index(TyG index)(r=-0.120,P＜0.05)and NC(r=-0.168,P＜0.05)were negatively correlated.In subjects with diabetes,NC was positively correlated with triglyc-erides(TG)(r=-0.100,P＜0.05),homeostasis model assessment of insulin resistance(HOMA-R)(r=-0.163,P＜0.05),total cholesterol/high-density lipoprotein(TC/HDL-C)(r=-0.214,P＜0.05)and TyG index(r=-0.156,P＜0.05).Conclusions Increased frequency of exercise is associated with reduced NC,improved insulin resistance,and cardiovascular risk factors in subjects of our team with newly diagnosed diabetes.Exercise has no significant effect on insulin resistance of subjects with normal glucose tolerance and pre-diabetes.