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Abstract Background Bladder cancer (BC) is a prevalent malignancy characterized by significant cellular heterogeneity. While single-cell multi-omics studies have provided valuable insights, much of the existing data remains underexplored, limiting our understanding of BC’s molecular mechanisms. Uncovering the pathogenesis of BC and finding new treatment methods are urgent problems to be solved. This study aims to address this gap by re-analyzing available single-cell datasets to uncover novel insights into BC. Methods In this study, we retrieved three single-cell transcriptome datasets by searching the Gene Expression Omnibus (GEO) database, focusing on single-cell sequencing of normal mouse bladder within the past 5 years. Through quality control and batch effect elimination, we obtained a total of 24,930 cells including epithelial, stromal, and immune cells. Subgroup analysis, pseudotemporal analysis, cell–cell communication, and transcription factor analysis were conducted specifically on epithelial cells to identify a transitional state during basal cell differentiation. We further compared the expression profiles of key transcription factors in cancer and normal tissues. In addition, we also performed immunohistochemical staining and survival analysis for key transcription factors. Results Subgroup analysis revealed multiple subtypes of epithelial cells, including basal, umbrella, and intermediate cells. Through pseudotemporal analysis, we discovered the developmental trajectory from basal cells to umbrella cells and further found that Basal_I is a transitional state for basal cell differentiation. Cell-to-cell communication analyses highlighted the pivotal role of Basal_I in cell–cell interactions, and key ligand-receptor pairs associated with cancer progression were also identified. Furthermore, elevated expression levels of key transcription factors in Basal_I were found to be closely associated with the stage and prognosis of BC. Immunohistochemical staining results further confirmed the upregulated expression of these transcription factors in BC. Conclusions Collectively, we found a transitional state of basal cells in normal bladder epithelial cells in mice, which may be related to the occurrence and development of BC, providing important clues for further understanding of the pathogenesis of BC. Our study provided possible molecular mechanisms or target for the research and treatment of BC.

Abstract Purpose The advantages of en bloc resection of bladder tumors (ERBT) over transurethral resection of bladder tumors (TURBT) in terms of patient prognosis are not yet clear, and there are some technical limitations. We aimed to compare the tumor recurrence in non-muscle invasive bladder cancer (NMIBC) patients with tumor diameter ≥ 3 cm undergoing either TURBT or thulium laser ERBT. Methods The patients included were those diagnosed with NMIBC based on pathological confirmation and underwent TURBT or modified thulium laser ERBT in the Department of Urology at Tongji Hospital from 2019 to 2024. The patients’ medical records were meticulously collected and postoperative follow-up was diligently conducted by trained personnel. Recurrence-free survival curves were generated utilizing the Kaplan–Meier method, and group comparisons were performed using the log-rank trend test. To minimize biases, we employed stratified survival analysis, alongside univariate and multivariate Cox regression analysis. Results This study included a total of 396 patients with NMIBC, with 214 undergoing TURBT and 182 undergoing ERBT. For all patients, there was no significant difference (P = 0.180) in RFS between the TURBT and ERBT groups. For patients with tumor diameter ≥ 3 cm, stratified analysis revealed that the RFS of the ERBT group was significantly better than that of the TURBT group (P = 0.033). However, in patients with tumor diameter

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.

Abstract Contrast-enhanced magnetic resonance neurography (CE-MRN) holds promise for diagnosing brachial plexopathy by enhancing nerve visualization and revealing additional imaging features in various lesions. This study aims to validate CE-MRN’s efficacy in improving brachial plexus (BP) imaging across different patient cohorts. Seventy-one subjects, including 19 volunteers and 52 patients with BP compression/entrapment, injury, and neoplasms, underwent both CE-MRN and plain MRN. Two radiologists assessed nerve visibility, with inter-reader agreement evaluated. Quantitative parameters such as signal intensity (SI), contrast-to-noise ratio (CNR), and contrast ratio (CR) of the C7 nerve were measured. Both qualitative scoring and quantitative metrics were compared between CE-MRN and plain MRN within each patient group. Patient classification followed the Neuropathy Score Reporting and Data System (NS-RADS), summarizing additional imaging features for each brachial plexopathy type. Inter-reader agreement for qualitative assessment was strong. CE-MRN significantly enhanced BP visualization and nerve-tissue contrast across all cohorts, particularly in volunteers and patients with injuries. It also uncovered additional imaging features such as hypointense signals in ganglia, compressed nerve sites, and neoplastic enhancements. CE-MRN effectively mitigated muscle edema and vascular contamination, enabling precise classification of BP injuries. Overall, CE-MRN consistently enhances BP visualization and provides valuable imaging features for accurate diagnosis.

Abstract Background Fusobacterium necrophorum (F. necrophorum)-induced necrotizing pneumonia is a rare but severe pulmonary infection. Insufficient microbiological detection methods can lead to diagnostic difficulties. Methods We report a case of F. necrophorum lung abscess diagnosed by next-generation sequencing (NGS) of bronchoalveolar lavage fluid (BALF). Results BALF-NGS detected F. necrophorum, guiding subsequent targeted antibiotic therapy. With active drainage and metronidazole treatment, the patient’s condition was effectively treated. Conclusion BALF-NGS is a valuable tool for the rapid diagnosis of infections caused by difficult-to-culture bacteria. It played a decisive role in the early identification of F. necrophorum, enabling timely and targeted antibiotic intervention. Early diagnosis and appropriate treatment are crucial for the management of F. necrophorum pneumonia.

Titanium alloy has excellent performance and wide application prospects in the aerospace, energy, chemical industry, and other areas. However, low hardness and poor wear resistance severely limit the application range of titanium alloys. Therefore, in the present research, multi-flow channel electrode and gas-liquid atomization medium are used for surface strengthening of Ti–6Al–4V alloy by electrical discharge machining (EDM). Benefiting from the multi-flow channel electrode, the gas-liquid atomization medium passes into the discharge gap uniformly. Under the environment of transient high-temperature and high-pressure generated by discharge, the ionized element N and molten titanium in the atomizing medium are induced to undergo in-situ synthesis reactions and generate a nitride reinforcement layer. Influence parameters such as peak current, pulse on time (Ton), and pulse off time (Toff) on the surface characteristics are optimized through single-factor experiments. Scanning electron microscope (SEM) and X-ray diffractometer (XRD) are adopted to investigate the hardness and wear resistance characteristics of the strengthening surface. The results indicate that a continuous and uniform reinforcement layer with fewer defects can be obtained. TiN and other hard phases are observed in the strengthened surface. The hardness of the strengthening layer is about 3–5 times as much as that of the substrate, and the wear resistance is increased by more than 40 %. Electrochemical analysis shows that the corrosion tendency of the strengthened layer decreased by 72 % compared to that of the substrate.

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.

Abstract Scimitar syndrome is a rare congenital anomaly characterized by partial or total anomalous pulmonary venous drainage of the right lung to the inferior vena cava. We report a case of a 67‐year‐old female who presented with cough and dyspnea and was diagnosed with scimitar syndrome and pulmonary arterial hypertension based on comprehensive imaging and hemodynamic evaluation. This case highlights the importance of considering scimitar syndrome as a cause of pulmonary hypertension even in adult patients.

With the increase in studies on high-entropy alloys and their impressive structural properties, the preparation processes and applications of high-entropy alloys have become a popular research topic in metallic materials. In this paper, the preparation of FeCrNiCoMnSi0.1 high-entropy alloy coatings was carried out by the follow-welding high-frequency power ultrasonic impact composite TIG arc melting process, the effects of different power ultrasonic impacts on the microstructure and properties of the coatings are investigated. The results showed that the average grain size is reduced by 74 % (from 278 μm to 72 μm), the average microhardness is increased by 41 % from 568 HV1 to 807 HV1, the abrasion resistance is improved by 68 % under the effect of ultrasonic impact. The ultrasonic impact treatment process can effectively refine the microstructure of the coatings and improve the strength of grain boundaries. The corrosion resistance of the coating in 3.5 wt% NaCl solution is enhanced by 65 %, the corrosion type was changed from intergranular corrosion to uniform corrosion. This is mainly caused by the ultrasonic impact treatment which suppresses the elemental segregation of Cr and Mn and improves the grain boundary strength.

Abstract Background Circular RNAs (circRNAs) have risen to prominence as important regulators of biological processes. This study investigated whether circGNB1 functions as a competitive endogenous RNA to regulate the pathological process of oxidative stress in age‐related osteoarthritis (OA). Methods The relationship between circGNB1 expression and oxidative stress/OA severity was determined in cartilages from OA patients at different ages. The biological roles of circGNB1 in oxidative stress and OA progression, and its downstream targets were determined using gain‐ and loss‐of‐function experiments in various biochemical assays in human chondrocytes (HCs). The in vivo effects of circGNB1 overexpression and knockdown were also determined using a destabilization of the medial meniscus (DMM) mouse model. Results Increased circGNB1 expression was detected in HCs under oxidative and inflammatory stress and in the cartilage of older individuals. Mechanistically, circGNB1 sponged miR‐152‐3p and thus blocked its interaction with its downstream mRNA target, ring finger protein 219 (RNF219), which in turn stabilized caveolin‐1 (CAV1) by preventing its ubiquitination at the K47 residue. CircGNB1 inhibited IL‐10 signalling by antagonizing miR‐152‐3p‐mediated RNF219 and CAV1 inhibition. Consequently, circGNB1 overexpression promoted OA progression by enhancing catabolic factor expression and oxidative stress and by suppressing anabolic genes in vitro and in vivo. Furthermore, circGNB1 knockdown alleviated the severity of OA, whereas circGNB1 overexpression had the opposite effect in a DMM mouse model of OA. Conclusion CircGNB1 regulated oxidative stress and OA progression via the miR‐152‐3p/RNF219/CAV1 axis. Modulating circGNB1 could be an effective strategy for treating OA.

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 and Objectives: Fractures are common in pediatric trauma, and they are caused by a broad spectrum of factors. Only a few studies have discussed the mechanisms of injury and their relationships to different types of fractures. The most frequent type of fractures in different age groups remains unclear. Therefore, we aim to summarize the epidemiological characteristics of pediatric fractures in a medical center in Zhuhai, China from 2006 to 2021 and analyze the causes of fractures with the highest frequency in different age groups. Materials and Methods: We extracted the information from the Zhuhai Center for Maternal and Child Health Care of those under 14 years old who had fractures from 2006 to 2021. Results: We reviewed the information of 1145 children. The number of patients increased during the 15 years (p < 0.0001). The number of patients was significantly different between genders after Y2 (p = 0.014). In addition, more than two-thirds of patients (71.3%) had upper limb fractures, and all types of falls were the most common cause of fractures (83.6%). The incidence demonstrated an insignificant difference in age groups except for the fractures of humerus and radius. Moreover, we discovered that the prevalence of fall-related injuries decreased with age, while that of sports-related injuries increased with age. Conclusions: Our study demonstrates that the prevalence of fall-related injuries decreases with age, and that of sports-related injuries increases with age. Most patients have upper limb fractures, and all types of falls are the most common cause of fractures. Fracture types with the highest frequency differ in each age group. These findings might supplement current epidemiological knowledge of childhood fracture and provide references for decision-making in children’s health policies.

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

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction–compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions.

Intervertebral disk degeneration (IVDD) is a spinal disk condition caused by an inflammatory response induced by various proinflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. cyclin-dependent kinase 9 (CDK9) is a transcriptional regulator and potential therapeutic target for many diseases, especially in regulating the activation of primary inflammatory response genes. Our study investigated a highly selective CDK9 inhibitor, atuveciclib, which protects nucleus pulposus (NP) cells from proinflammatory stimuli-induced catabolism. The effects of CDK9 inhibition were determined in human and rat NP cells treated with IL-1β in the presence or absence of atuveciclib or small interfering RNA target CDK9. Inhibition of CDK9 led to the attenuation of inflammatory response. In addition, rat intervertebral disk (IVD) explants were used to determine the role of CDK9 inhibition in extracellular matrix degradation. The rat IVDD model also proved that CDK9 inhibition attenuated IVDD, as validated using magnetic resonance imaging and immunohistochemistry. Taken together, CDK9 is a potential therapeutic target to prevent IVDD.

Aim. To analyze changes in peripheral blood monocytes and their clinical significance in patients with early stage of idiopathic membranous nephropathy (IMN). Methods. A total of 27 patients with early stage of IMN and 16 age- and sex-matched healthy controls (HCs) were recruited for the study. The monocyte subset counts in circulation were measured by flow cytometry, and serum interleukin- (IL-) 10 and IL-12 concentrations were tested by enzyme-linked immunosorbent assay. The potential association between clinical signs and monocyte subset counts was analyzed statistically. Results. Compared with the HCs, the patients with early stage of IMN had higher counts of CD14+CD163+, CD14+CD163+CD206+, and CD14+CD163+CD206+CD115+ M2-like monocytes. The CD14+CD163+CD206+ M2-like cell counts and intracellular IL-10 concentrations in the monocytes were positively correlated with progression in proteinuria. The levels of serum IL-10 were significantly higher in early IMN patients than in the HCs. Furthermore, CD14+CD163+CD206+ M2-like cell counts in the patients with incipient IMN were also positively related with 24 h urinary albumin levels and the values of serum M-type phospholipase A2 receptor (PLA2R). Conclusion. CD14+CD163+CD206+ M2-like monocytes may contribute to the pathologic process in early-stage IMN and could serve as potential markers for evaluating the disease severity.