BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

Objective To explore the application effect of a standardized management method based on failure mode and effect analysis （FMEA） in optimizing the whole-process quality control system of the intravenous admixture service （PIVAS）. Methods The quality control management system of the PIVAS was optimized by establishing six quality control groups led by the head nurse, with full participation of pharmacy, nursing, and logistical staff, ensuring comprehensive coverage and traceability of all quality control links. Each group conducted risk priority number （RPN） scoring for potential failure modes in their respective quality control processes, and targeted improvement measures were formulated based on the scoring results. The RPN values of failure modes and quality control-related evaluation indicators before and after implementation were compared to achieve closed-loop management. Results After one year of management, the RPN values of the six major failure modes significantly decreased compared to those before implementation （P<0.05）. The compounding error rate dropped to 0.13%, the dispensing error rate decreased to 0.95%, the compounding efficiency increased to 98%, the delivery time was shortened by 0.45 h per batch, the intervention rate for irrational prescriptions rose to 94.87%, satisfaction improved to 96.78%, and the participation rate of quality control personnel reached 95.36% （P<0.05）. Conclusion FMEA-based identification of potential failure modes in the whole-process quality control system of the IVAS, combined with risk quantification and targeted interventions, significantly reduced high-risk failure modes, improved compounding accuracy and efficiency, and ensured the safety of clinical intravenous medication and the effectiveness of healthcare quality management.

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 analyze the implementation status and challenges of sex education in special education schools, so as to provide a scientific basis for formulating effective promotion strategies. Methods: From November 2023 to January 2024, a census survey was conducted among 120 in service teachers from 7 special education schools in Luzhou. The questionnaire covered the current status of sex education in schools, teachers attitudes and knowledge toward sex education, and their coping methods for students inappropriate sexual behaviors. Results: About 77.5% of teachers reported having provided sex education to students, but 93.2% indicated a lack of specialized sex education textbooks for special children, 90.4% reported no full time teachers for sex education, and the methods of sex education were relatively limited (50.0% mainly based on lecture method). Nearly 95.8% of teachers held a positive attitude toward sex education, with 98.3% supporting its implementation. Only 26.7% of teachers demonstrated a good grasp of sex education knowledge, with the best understood topic being "recognition and protection of private parts" (21.6%). When dealing with students inappropriate sexual behaviors, the active response rate of teachers was 23.9%, with the highest active response rate observed for "intentionally hugging or kissing the opposite sex" (39.7%). Conclusions The special education schools in Luzhou lack comprehensive sex education curricula, teaching materials and full time teachers, sufficient knowledge among teachers, and adequate proactive responses to students inappropriate sexual behaviors. Greater emphasis should be placed on sex education for special children, including the training of dedicated teachers, to provide comprehensive and high quality sex education services for special children.

OBJECTIVE To explore the distribution and drug resistance of pathogens isolated from the diabetes mel-litus patients complicated with skin soft tissue infections(SSTI)so as to provide guidance for reasonable clinical use of antibiotics.METHODS A total of 1177 diabetes mellitus patients with SSTI who were hospitalized in endo-crinology department of Zhongda Hospital Affiliated to Southeast University from Jan.2016 to Dec.2023 were re-cruited as the research subjects.The wound secretion specimens were cultured for pathogens,and the drug suscep-tibility testing was performed.The pathogens isolated in the 8 years and the results of drug susceptibility testing for the main pathogens were divided into the first 4-year group(from 2016 to 2019)and the last 4-year group(from 2020 to 2023).RESULTS Among the 1177 patients with SSTI,the patients with diabetic foot infections ac-counted for 76.10％.Among the 1383 strains of isolated pathogens,there were 815(58.93％)strains of gram-positive bacteria,529(38.25％)strains of gram-negative bacteria,and 39(2.82％)strains of fungi.The constitu-ent ratio of Staphylococcus aureus strains of the last 4-year group was lower than that of the first 4-year group,while the constituent ratio of Pseudomonas aeruginosa strains of the last 4-year group was higher than that of the first 4-year group(P＜0.05).The drug resistance rate of the S.aureus strains to oxacillin and the drug resistance rate of Streptococcus agalactiae strains to erythromycin were increased,and the drug resistance rate of Escherichia coli strains to ampicillin-sulbactam was increased(P＜0.05).The P.aeruginosa strains that were resistant to piperacillin-tazobac-tam,ceftazidime,cefepime,tobramycin,gentamycin,amikacin,ciprofloxacin and levofloxacin were detected in the last 4-year group.Among 7 strains of Candida glabrata,1 strain was resistant to fluconazole,and 2 strains were resistant to itraconazole.CONCLUSIONS There are a great variety of pathogens isolated from the diabetes mellitus patients complicated with SSTI,the gram-positive bacteria are dominant.The drug resistance rates of the major species of pathogens are remarkably higher in the last 4-year group than in the first 4-year group.

Objective:To Analyze the psychological behavior characteristics of young military personnel stationed in Xinjiang,providing a basis for the mental health education of military personnel.Methods:Using the Symptom Checklist-90(SCL-90)and a cluster sampling method,the mental health screening of young military personnel in Xinjiang was conducted from July to August 2024,with 2 218 valid questionnaires collected.Total scores and subscale scores of the SCL-90 were compared across demographic variables,including ethnicity,personnel categories,education level,marital status,singleton status,and urban/rural background.Results:The positive symptom rate was 1.53%(34/2218).Statistically significant differences(P＜0.05)were observed in total SCL-90 scores and subscale scores among the young military personnel with different ethnicities,personnel categories,education levels,marital statuses,singleton statuses,etc.Conclusions:To address the evolving demands of military psychological services,frontline-oriented interventions should be prioritized,leveraging the roles of psychologists and mental health officers.Institutional safeguards for basic needs,enhanced military support systems,and strengthened humanistic care are critical to improving psychological resilience among personnel,thereby bolstering combat readiness and stability.

OBJECTIVE To analyze the clinical characteristics of the 12 patients tested with Candida auris in a three-A hospital so as to provide guidance for prevention and control of nosocomial C.auris infection.METHODS The specimens sources and departments where the C.auris strains were isolated as well as the drug resistance were retrospectively collected from Zhongda Hospital Affiliated to Southeast University between Sep.2023 and Jun.2024.The clinical characteristics of the patients with C.auris infection were summarized.The epidemiological survey was conducted for the possibility of its transmission in hospitals,and the corresponding modified preven-tion measures were put forward.RESULTS Among the 12 patients who were tested with C.auris,10 were male,and 2 were female;the age ranged between 21 and 92 years old.Most of the patients were complicated with multi-ple underlying diseases and had the history of repeated hospitalization as well as the history of invasive operation procedures such as tracheotomy,urinary catheterization,gastric tube indwelling and venoarterial catheterization;in the meantime,other multidrug-resistant organisms(MDROs)and fungi were tested in those patients,and the patients used multiple types of antibiotics.Totally 16 strains of C.auris were isolated from the 12 patients with C.auris tested,62.50％(10/16)of which were isolated from urine specimens,18.75％(3/16)were isolated from sputum specimens,and 6.25％(1/16)were isolated from deep venous catheter,tissue biopsy and wound swab specimens.All of the 16 strains of C.auris were resistant to fluconazole and sensitive to caspofungin;4 strains were resistant to amphotericin B.Totally 2 patients had Candida auris infection,one was pulmonary infection,and the other was urinary tract infection,and the infection rate was 16.67％;both patients were cured.There were 10 cases of colonization,and the colonization rate was 83.33％.The result of epidemiological survey indicated that the C.auris that was tested in the No.8 patient may originate from the No.4 patient who carelessly brought from outside the hospital due to poor implementation of standardized prevention measures.CONCLUSIONS The patients tested with C.auris usually have complicated medical backgrounds.Although the colonized C.auris strains are dominant among the strains in the hospital,the related departments need to intensify the implementation of pre-vention measures so as to prevent the transmission of C.auris and pay special attention to the early identification and management of imported pathogens.