Second People’s Hospital of Huai’an

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable therapeutic efficacy in treating cancer and autoimmune diseases. However, current CAR-T cell therapy requires ex vivo T cell engineering, which is both time-consuming and cost-prohibitive, adding complexity to the overall treatment. In this study, using an engineered Sindbis virus envelope, we developed a lentiviral vector system with high specificity for targeting human T cell line and primary T cells, but not targeting other immune cell subsets. Notably, this T cell-specific lentiviral vector does not require additional anti-CD3/CD28 stimulation for primary T cell activation during infection in vitro. Furthermore, the lentiviral vector successfully delivered a CD19-targeting CAR molecule to human primary T cells in vivo. The in vivo generated CD19-CAR-T cells efficiently mediated B cell lymphoma clearance. Overall, our study provides a promising tool for the development of in vivo T cell engineering approaches.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-17342-1.

PurposeAdenomyosis and endometriosis are both recognized as etiological factors in the development of dysmenorrhea; however, their respective contributions to this condition remains ambiguous. This study aims to examine the distinct contributions of adenomyosis and endometriosis to the symptomatology of dysmenorrhea.Patients and MethodsA total of 480 women undergoing laparoscopy for benign conditions were included, among whom 238 were diagnosed with endometriosis and 236 with adenomyosis. Preoperative assessments of general pain severity of dysmenorrhea and 18 specific menstrual symptoms were conducted utilizing the Visual Analog Scale (VAS) and the COX Menstrual Symptom Scale. Symptom clusters were identified using correlation analyses, hierarchical cluster analysis and graphical least absolute shrinkage and selection operator (GLASSO) network analysis. These clusters were further corroborated by examining the varied correlations between symptoms and VAS scores using Spearman correlation, as well as the distinct patterns of how adenomyosis-related key uterine dimension and endometriosis affected these symptoms through logistic regression analysis.ResultsThree distinct clusters of menstrual symptoms were identified. One cluster, which included cramps, nausea, vomiting, loss of appetite, stomachache, and insomnia, demonstrated a close correlation with VAS pain scores. The symptoms within this cluster were influence by common influencing factors, particularly increased uterine anteroposterior diameter and the presence of endometriosis, with a consistent pattern. These characteristics substantiate the classification of these symptoms as the core dysmenorrhea cluster. Although endometriosis exacerbated these symptoms, their severity was not further amplified by higher revised American Society for Reproductive Medicine (rASRM) scores.ConclusionMenstrual symptoms can be primarily categorized into three distinct clusters, with one cluster potentially representing the core symptoms associated with dysmenorrhea. An increased uterine anteroposterior diameter, probably attributed to adenomyosis, serve as a significant imaging correlate of dysmenorrhea severity, while endometriosis primarily acts to exacerbate them.

This letter evaluates Deng et al study examining the gut microbiota and metabolite changes in metastatic colorectal cancer (CRC). The research used 16S rRNA sequencing and liquid chromatography-mass spectrometry metabolomics to investigate microbial and metabolic shifts in patients with metastatic vs non-metastatic CRC. The study reveals that CRC patients with metastasis exhibit significant differences in their gut microbiota and metabolites compared to non-metastatic patients. However, the study’s reliance on 16S rRNA sequencing presents inherent limitations, particularly with respect to species-level resolution. The sequencing depth may not have been sufficient to capture all relevant low-abundance taxa, as indicated by the rarefaction curves which did not fully plateau, potentially affecting the identification of differential species. It also identifies 91 differential metabolites, particularly those involved in nucleic acid, alkaloid, and lipid metabolism, which may contribute to metastasis progression. The findings suggest that microbiota and their metabolites play a critical role in CRC metastasis, offering potential targets for diagnosis and treatment. However, several limitations exist, including small sample size, single-center data, and a cross-sectional design that prevents causal conclusions. Additionally, the study lacks integration of key clinical factors such as dietary patterns and medication use, which could confound the results. Future research should expand these findings through multi-center studies with longer follow-up periods, incorporating more comprehensive clinical data and advanced analytical techniques to validate and refine the role of microbiota and metabolites in CRC metastasis. Despite its limitations, this study provides valuable insights into the microbiota-metabolite axis in CRC metastasis and opens potential avenues for future research. However, it is crucial to note that the metabolite identification was based on database matching rather than chemical standard validation. As such, these results should be considered putative annotations, with their accuracy requiring further confirmation through targeted analyses.

Dwarfism, a condition characterized by short stature, has been the focus of therapeutic advancements with the emergence of novel peptide drugs. Vosoritide, indicated for certain types of dwarfism, has shown therapeutic potential in clinical trials. However, a comprehensive safety profile is essential for its clinical application. The current literature lacks a detailed assessment of vosoritide's safety, indicating a significant gap that this study aims to address. We conducted a retrospective pharmacovigilance study by analyzing the FDA Adverse Event Reporting System (FAERS) database to evaluate adverse events (AEs) associated with vosoritide monotherapy. The study employed a case/non-case methodology and applied signal detection algorithms, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS), to identify AE signals related to vosoritide use. The study included 9319269 reports from the FAERS database, covering the period from 2022 to 2023, with 274 reports specifically citing vosoritide. A significant number of AEs were identified, with a notable incidence in the pediatric population. The most frequently reported AEs were related to endocrine disorders, including altered growth hormone levels and glucose homeostasis issues. Other affected system organ classes (SOCs) were infections and infestations, as well as skin and subcutaneous tissue disorders. Specific preferred terms (PTs) associated with vosoritide included "growth deceleration," "glycemic dysregulation," and "local injection site reactions." The findings from this study underscore the importance of close monitoring of vosoritide treatment, particularly in pediatric patients. The identification of both expected and unexpected AEs highlights the necessity for ongoing pharmacovigilance and further research to fully understand the safety profile of vosoritide in clinical practice. This study contributes to the broader field by emphasizing the critical need for patient safety considerations in the development of new therapeutic agents.