Non-obstructive azoospermia is the most challenging type of male infertility. Stem cell based therapy provides the potential to enhance the recovery of spermatogenesis following cancer therapy. Bone marrow-derived mesenchymal stem cells (BMSCs) possess the potential to differentiate or trans-differentiate into multi-lineage cells, secrete paracrine factors to recruit the resident stem cells to participate in tissue regeneration, or fuse with the local cells in the affected region. In this study, we tested whether spermatogenically-induced BMSCs can restore spermatogenesis after administration of an anticancer drug. Allogeneic BMSCs were co-cultured in conditioned media derived from cultured testicular Sertoli cells in vitro, and then induced stem cells were transplanted into the seminiferous tubules of a busulfan-induced azoospermatic rat model for 8 weeks. The in vitro induced BMSCs exhibited specific spermatogonic gene and protein markers, and after implantation the donor cells survived and located at the basement membranes of the recipient seminiferous tubules, in accordance with what are considered the unique biological characteristics of spermatogenic stem cells. Molecular markers of spermatogonial stem cells and spermatogonia (Vasa, Stella, SMAD1, Dazl, GCNF, HSP90α, integrinβ1, and c-kit) were expressed in the recipient testis tissue. No tumor mass, immune response, or inflammatory reaction developed. In conclusion, BMSCs might provide the potential to trans-differentiate into spermatogenic-like-cells, enhancing endogenous fertility recovery. The present study indicates that BMSCs might offer alternative treatment for the patients with azoospermatic infertility after cancer chemotherapy.

ChatGPT, an AI-driven conversational large language model (LLM), has garnered significant scholarly attention since its inception, owing to its manifold applications in the realm of medical science. This study primarily examines the merits, limitations, anticipated developments, and practical applications of ChatGPT in clinical practice, healthcare, medical education, and medical research. It underscores the necessity for further research and development to enhance its performance and deployment. Moreover, future research avenues encompass ongoing enhancements and standardization of ChatGPT, mitigating its limitations, and exploring its integration and applicability in translational and personalized medicine. Reflecting the narrative nature of this review, a focused literature search was performed to identify relevant publications on ChatGPT’s use in medicine. This process was aimed at gathering a broad spectrum of insights to provide a comprehensive overview of the current state and future prospects of ChatGPT in the medical domain. The objective is to aid healthcare professionals in understanding the groundbreaking advancements associated with the latest artificial intelligence tools, while also acknowledging the opportunities and challenges presented by ChatGPT.

Background: Exosomes derived from mesenchymal stem cells (MSCs) have shown to have effective application prospects in the medical field, but exosome yield is very low. The production of exosome mimetic vesicles (EMVs) by continuous cell extrusion leads to more EMVs than exosomes, but whether the protein compositions of MSC-derived EMVs (MSC-EMVs) and exosomes (MSC-exosomes) are substantially different remains unknown. The purpose of this study was to conduct a comprehensive proteomic analysis of MSC-EMVs and MSC-exosomes and to simply explore the effects of exosomes and EMVs on wound healing ability. This study provides a theoretical basis for the application of EMVs and exosomes. Methods: In this study, EMVs from human umbilical cord MSCs (hUC MSCs) were isolated by continuous extrusion, and exosomes were identified after hUC MSC ultracentrifugation. A proteomic analysis was performed, and 2315 proteins were identified. The effects of EMVs and exosomes on the proliferation, migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated by cell counting kit-8, scratch wound, transwell and tubule formation assays. A mouse mode was used to evaluate the effects of EMVs and exosomes on wound healing. Results: Bioinformatics analyses revealed that 1669 proteins in both hUC MSC-EMVs and hUC MSC-exosomes play roles in retrograde vesicle-mediated transport and vesicle budding from the membrane. The 382 proteins unique to exosomes participate in extracellular matrix organization and extracellular structural organization, and the 264 proteins unique to EMVs target the cell membrane. EMVs and exosomes can promote wound healing and angiogenesis in mice and promote the proliferation, migration and angiogenesis of HUVECs. Conclusions: This study presents a comprehensive proteomic analysis of hUC MSC-derived exosomes and EMVs generated by different methods. The tissue repair function of EMVs and exosomes was herein verified by wound healing experiments, and these results reveal their potential applications in different fields based on analyses of their shared and unique proteins.

Osteosarcoma is a bone tumor with a high incidence in children and adolescents. Chemotherapy for osteosarcoma is limited, and effective targeted drugs are urgently needed to treat osteosarcoma. Exosomes as a natural nano drug delivery platform have been widely studied and proven to have good drug delivery performance. However, the low production of exosomes hinders its development as a carrier. Exosome mimetics (EMs) as an alternative product of exosomes solve the problem of low production of exosomes and maintain the good performance of exosomes as carriers. In this study, bone marrow mesenchymal stem cells (BMSCs) were sequentially extruded to generate EMs to encapsulate doxorubicin (EM-Dox) to treat osteosarcoma. The results showed that we successfully prepared EMs of BMSC, and EM-Dox was prepared using an active-loading approach. Our engineered EM-Dox demonstrated significantly more potent tumor inhibition activity and fewer side effects than free doxorubicin. This novel biological nanomedicine system provides a promising opportunity to develop novel precision medicine for osteosarcoma.

Background: Osteosarcoma (OSC) and Ewing's sarcoma (EWS) are children's most common primary bone tumors. The purpose of the study is to develop and validate a new nomogram to predict the cancer-specific survival (CSS) of childhood OSC and EWS.Methods: The clinicopathological information of all children with OSC and EWS from 2004 to 2018 was downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were used to screen children's independent risk factors for CSS. These risk factors were used to construct a nomogram to predict the CSS of children with OSC and EWS. A series of validation methods, including calibration plots, consistency index (C-index), and area under the receiver operating characteristic curve (AUC), were used to validate the accuracy and reliability of the prediction model. Decision curve analysis (DCA) was used to validate the clinical application efficacy of predictive models. All patients were divided into low- and high-risk groups based on the nomogram score. Kaplan-Meier curve and log-rank test were used to compare survival differences between the two groups.Results: A total of 2059 children with OSC and EWS were included. All patients were randomly divided into training cohort 60% (N = 1215) and validation cohort 40% (N = 844). Univariate and multivariate analysis suggested that age, surgery, stage, primary site, tumor size, and histological type were independent risk factors. Nomograms were established based on these factors to predict 3-, 5-, and 8-years CSS of children with OSC and EWS. The calibration plots showed that the predicted value was highly consistent with the actual value. In the training cohort and validation cohort, the C-index was 0.729 (0.702–0.756) and 0.735 (0.702–0.768), respectively. The AUC of the training cohort and the validation cohort also showed similar results. The DCA showed that the nomogram had good clinical value.Conclusion: We constructed a new nomogram to predict the CSS of OSC and EWS in children. This predictive model has good accuracy and reliability and can help doctors and patients develop clinical strategies.

Regulated cell death (RCD) is crucial for the elimination of abnormal cells. In recent years, strategies aimed at inducing RCD, particularly apoptosis, have become increasingly important in cancer therapy. However, the ability of tumor cells to evade apoptosis has led to treatment resistance and relapse, prompting extensive research into alternative death processes in cancer cells. A recent study identified a novel form of RCD known as disulfidptosis, which is linked to disulfide stress. Cancer cells import cystine from the extracellular environment via solute carrier family 7 member 11 (SLC7A11) and convert it to cysteine using nicotinamide adenine dinucleotide phosphate (NADPH). When NADPH is deficient or its utilization is impaired, cystine accumulates, leading to the formation of disulfide bonds in the actin cytoskeleton, triggering disulfidptosis. Disulfidptosis reveals a metabolic vulnerability in tumors, offering new insights into cancer therapy strategies. This review provides a detailed overview of the mechanisms underlying disulfidptosis, the current research progress, and limitations. It also highlights innovative strategies for inducing disulfidptosis and explores the potential of combining these approaches with traditional cancer therapies, particularly immunotherapy, to expedite clinical translation.