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Abstract Background Aging of the male prostate is an inevitable process in which the prostate undergoes hyperplasia, and this growth may lead to compression of the urethra, resulting in voiding dysfunction and associated symptoms, and an increased risk of prostate cancer. Despite the significance of prostate aging, the molecular mechanisms involved are still not fully understood. Methods Prostate split by lobes from young (2 months) and aged (24 months) mice were collected for single-cell RNA sequencing (scRNA-seq) analysis. Tissues from both anterior prostate (AP) and ventral/dorsal/lateral prostate (VDLP) were included in the study. Data analysis included unsupervised clustering using the uniform manifold approximation and projection (UMAP) algorithm to identify distinct cell types based on marker gene expression. Differential gene expression analysis was performed to identify age-related changes in gene expression across different cell types. Functional enrichment analysis was conducted to elucidate biological pathways associated with differentially expressed genes. Additionally, cellular interactions and developmental trajectories were analyzed to characterize cellular dynamics during prostate aging. Results The single-cell transcriptome analysis of the mouse prostate during aging revealed heterogeneity across various cell types and their changes during the aging process. We found a significant increase in the proportion of mesenchymal and immune cells in aged mice. Our study unveiled alterations in genes and pathways associated with cellular senescence, oxidative stress, and regeneration in epithelial cells. Furthermore, we observed that basal cells may undergo epithelial-mesenchymal transition (EMT) to become mesenchymal cells, particularly prominent in aged mice. Additionally, immune cells, notably macrophages and T cells, exhibited a heightened inflammatory response in aged mice. Conclusion In summary, our study provides a comparative analysis of the single-cell transcriptome of the aged and young mice prostates, elucidating cellular and molecular changes between the aged and young mice prostates.

Background: Acute myeloid leukemia (AML) is the most common form of leukemia among adults and is characterized by uncontrolled proliferation and clonal expansion of hematopoietic cells. There has been a significant improvement in the treatment of younger patients, however, prognosis in the elderly AML patients remains poor.Methods: We used computational methods and machine learning (ML) techniques to identify and explore the differential high-risk genes (DHRGs) in AML. The DHRGs were explored through multiple in silico approaches including genomic and functional analysis, survival analysis, immune infiltration, miRNA co-expression and stemness features analyses to reveal their prognostic importance in AML. Furthermore, using different ML algorithms, prognostic models were constructed and validated using the DHRGs. At the end molecular docking studies were performed to identify potential drug candidates targeting the selected DHRGs.Results: We identified a total of 80 DHRGs by comparing the differentially expressed genes derived between AML patients and normal controls and high-risk AML genes identified by Cox regression. Genetic and epigenetic alteration analyses of the DHRGs revealed a significant association of their copy number variations and methylation status with overall survival (OS) of AML patients. Out of the 137 models constructed using different ML algorithms, the combination of Ridge and plsRcox maintained the highest mean C-index and was used to build the final model. When AML patients were classified into low- and high-risk groups based on DHRGs, the low-risk group had significantly longer OS in the AML training and validation cohorts. Furthermore, immune infiltration, miRNA coexpression, stemness feature and hallmark pathway analyses revealed significant differences in the prognosis of the low- and high-risk AML groups. Drug sensitivity and molecular docking studies revealed top 5 drugs, including carboplatin and austocystin-D that may significantly affect the DHRGs in AML.Conclusion: The findings from the current study identified a set of high-risk genes that may be used as prognostic and therapeutic markers for AML patients. In addition, significant use of the ML algorithms in constructing and validating the prognostic models in AML was demonstrated. Although our study used extensive bioinformatics and machine learning methods to identify the hub genes in AML, their experimental validations using knock-out/-in methods would strengthen our findings.

Purpose: Carpal tunnel syndrome (CTS) is a common form of median nerve compression in the wrist caused by focal peripheral neuropathy. Platelet-rich plasma (PRP) therapy could improve the healing ability by exposing the injured tissues to high concentrations of autologous growth factors. Our study aims to compare all injective treatments for CTS and assess the efficacy and priority of PRP therapy.Methods: We searched Medline, Embase, Web of Science, Cochrane databases, and Clinicaltrial.gov until 17 October 2022. We only included data from randomized controlled trials (RCTs) that evaluated PRP injection therapy or drug injection therapy. The included RCTs measured at least one of the following three outcomes with validated instruments: in the visual analog scale (VAS), symptom severity scale (SSS), and functional status scale (FSS).Results: Overall, 19 studies with 1,066 patients were included in this study. We used the SUCRA rankings to determine the merits of various therapies. In all, 5% dextrose injections were the best treatment strategy for the VAS (MD −1.22, 95% CI −2.66 to 0.23; SUCRA = 79.2%), followed by triamcinolone (high-dose) injections (MD −0.69, 95% CI −2.11 to 0.73; SUCRA = 62.7%) and PRP injections (MD −0.39, 95% CI −1.67 to 0.89; SUCRA = 60.0%). In the SSS, the most effective intervention was hydroxyprogesterone injections (MD −0.62, 95% CI −1.09 to −0.16; SUCRA = 91.0%). The SUCRA ranking of PRP was second only to steroids and estrogen (MD −0.39, 95% CI −0.60 to −0.18; SUCRA = 60.8%). In the FSS, the best regimen strategy was hydroxyprogesterone injections (MD 0.12, 95% CI −0.30 to 0.54; SUCRA = 99.5%), followed by triamcinolone (low-dose) injections (MD −0.02, 95% CI −0.54 to 0.49; SUCRA = 87.4%) and PRP injections (MD −0.26, 95% CI −0.43 to −0.09; SUCRA = 77.1%).Conclusion: PRP is an alternative choice for CTS treatment. PRP injection is second only to steroids and estrogen in the treatment efficacy of CTS, with a wide indication and safe outcome.

Background: Tranexamic acid (TXA) has been applied in various types of surgery for hemostasis purposes. The efficacy and safety of TXA are still controversial in different surgeries. Guidelines for clinical application of TXA are needed.Materials and method: We systematically searched multiple medical databases for meta-analyses examining the efficacy and safety of TXA. Types of surgery included joint replacement surgery, other orthopedic surgeries, cardiac surgery, cerebral surgery, etc. Outcomes were blood loss, blood transfusion, adverse events, re-operation rate, operative time and length of hospital stay, hemoglobin (Hb) level, and coagulation function. Assessing the methodological quality of systematic reviews 2 (AMSTAR 2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) were used for quality assessment of the included meta-analyses. Overlapping reviews were evaluated by calculating the corrected covered area (CCA).Result: In all, we identified 47 meta-analyses, of which 44 of them were of “high” quality. A total of 319 outcomes were evaluated, in which 58 outcomes were assessed as “high” quality. TXA demonstrates significant hemostatic effects in various surgeries, with lower rates of blood transfusion and re-operation, shorter operative time and length of stay, and higher Hb levels. Besides, TXA does not increase the risk of death and vascular adverse events, but it is a risk factor for seizure (a neurological event) in cardiac surgery.Conclusion: Our study demonstrates that TXA has a general hemostatic effect with very few adverse events, which indicates TXA is the recommended medication to prevent excessive bleeding and reduce the blood transfusion rate. We also recommend different dosages of TXA for different types of adult surgery. However, we could not recommend a unified dosage for different surgeries due to the heterogeneity of the experimental design.Systematic Review Registration:clinicaltrials.gov/, identifier CRD42021240303