Investigating gene signatures associated with immunity in colon adenocarcinoma to predict the immunotherapy effectiveness using NFM and WGCNA algorithms.

Colon adenocarcinoma (COAD), a frequently encountered and highly lethal malignancy of the digestive system, has been the focus of intensive research regarding its prognosis. The intricate immune microenvironment plays a pivotal role in the pathological progression of COAD; nevertheless, the underlying molecular mechanisms remain incompletely understood. This study aims to explore the immune gene expression patterns in COAD, construct a robust prognostic model, and delve into the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby providing critical support for individualized treatment strategies and prognostic evaluation. Initially, we curated a comprehensive dataset by screening 2600 immune-related genes (IRGs) from the ImmPort and InnateDB databases, successfully obtaining a rich data resource. Subsequently, the COAD patient cohort was classified using the non-negative matrix factorization (NMF) algorithm, enabling accurate categorization. Continuing on, utilizing the weighted gene co-expression network analysis (WGCNA) method, we analyzed the top 5000 genes with the smallest p-values among the differentially expressed genes (DEGs) between immune subtypes. Through this rigorous screening process, we identified the gene modules with the strongest correlation to the COAD subpopulation, and the intersection of genes in these modules with DEGs (COAD vs COAD vs Normal colon tissue) is referred to as Differentially Expressed Immune Genes Associated with COAD (DEIGRC). Employing diverse bioinformatics methodologies, we successfully developed a prognostic model (DPM) consisting of six genes derived from the DEIGRC, which was further validated across multiple independent datasets. Not only does this predictive model accurately forecast the prognosis of COAD patients, but it also provides valuable insights for formulating personalized treatment regimens. Within the constructed DPM, we observed a downregulation of CALB2 expression levels in COAD tissues, whereas NOXA1, KDF1, LARS2, GSR, and TIMP1 exhibited upregulated expression levels. These genes likely play indispensable roles in the initiation and progression of COAD and thus represent potential therapeutic targets for patient management. Furthermore, our investigation into the molecular mechanisms and therapeutic targets for COAD liver metastasis revealed associations with relevant processes such as fat digestion and absorption, cancer gene protein polysaccharides, and nitrogen metabolism. Consequently, genes including CAV1, ANXA1, CPS1, EDNRA, and GC emerge as promising candidates as therapeutic targets for COAD liver metastasis, thereby providing crucial insights for future clinical practices and drug development. In summary, this study uncovers the immune gene expression patterns in COAD, establishes a robust prognostic model, and elucidates the molecular mechanisms and potential therapeutic targets for COAD liver metastasis, thereby possessing significant theoretical and clinical implications. These findings are anticipated to offer substantial support for both the treatment and prognosis management of COAD patients.

Balloon dilation for the treatment of male urethral strictures: a systematic review and meta-analysis.

OBJECTIVE: The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the safety, efficacy and factors influencing the clinical application of balloon dilation for the treatment of male urethral strictures. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, Web of Science, Cochrane Library and Scopus were searched for publications published before 17 July 2022. STUDY SELECTION: Two independent researchers screened and assessed the results, and all clinical studies on balloon dilation for the treatment of urethral strictures in men were included. DATA EXTRACTION AND SYNTHESIS: The success rate, rate of adverse events, International Prostate Symptom Scores, maximum uroflow (Qmax) and postvoid residual urine volume were the main outcomes. Stata V.14.0 was used for statistical analysis. RESULTS: Fifteen studies with 715 patients were ultimately included in this systematic review. The pooled results of eight studies showed that the reported success rate of simple balloon dilation for male urethral strictures was 67.07% (95% confidence interval [CI]: 55.92% to 77.36%). The maximum urinary flow rate at 3 months (risk ratio [RR]= 2.6510, 95% CI: 1.0681 to 4.2338, p<0.01) and the maximum urinary flow rate at 1 year (RR= 1.6637, 95% CI: 1.1837 to 2.1437, p<0.05) were significantly different after dilation. There is insufficient evidence to suggest that balloon dilation is superior to optical internal urethrotomy or direct visual internal urethrotomy (DVIU) (RR= 1.4754, 95% CI: 0.7306 to 2.9793, p=0.278). CONCLUSION: Balloon dilation may be an intermediate step before urethroplasty and is a promising alternative therapy to simple dilation and DVIU. The balloon is a promising drug delivery tool, and paclitaxel drug-coated balloon dilation is effective in reducing retreatment rates in patients with recurrent anterior urethral strictures. The aetiology, location, length, previous treatment of urethral stricture may be associated with the efficacy of balloon dilation. PROSPERO REGISTRATION NUMBER: CRD42022334403.

The Regenerative Microenvironment of the Tissue Engineering for Urethral Strictures.

Urethral stricture caused by various reasons has threatened the quality of life of patients for decades. Traditional reconstruction methods, especially for long-segment injuries, have shown poor outcomes in treating urethral strictures. Tissue engineering for urethral regeneration is an emerging concept in which special designed scaffolds and seed cells are used to promote local urethral regeneration. The scaffolds, seed cells, various factors and the host interact with each other and form the regenerative microenvironment. Among the various interactions involved, vascularization and fibrosis are the most important biological processes during urethral regeneration. Mesenchymal stem cells and induced pluripotent stem cells play special roles in stricture repair and facilitate long-segment urethral regeneration, but they may also induce carcinogenesis and genomic instability during reconstruction. Nevertheless, current technologies, such as genetic engineering, molecular imaging, and exosome extraction, provide us with opportunities to manage seed cell-related regenerative risks. In this review, we described the interactions among seed cells, scaffolds, factors and the host within the regenerative microenvironment, which may help in determining the exact molecular mechanisms involved in urethral stricture regeneration and promoting clinical trials and the application of urethral tissue engineering in patients suffering from urethral stricture.

Adipose stem cells in tissue regeneration and repair: From bench to bedside.

ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the "ADSCs-scaffold composite" into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.

Integrated analysis to identify the prognostic and immunotherapeutic roles of coagulation-associated gene signature in clear cell renal cell carcinoma.

The coagulation system is closely related to the physiological status and immune response of the body. Recent years, studies focusing on the association between coagulation system abnormalities and tumor progression have been widely reported. In clear cell renal cell carcinoma (ccRCC), poor prognosis often occurs in patients with venous tumor thrombosis and coagulation system abnormalities, and there is a lack of research in related fields. Significant differences in coagulation function were also demonstrated in our clinical sample of patients with high ccRCC stage or grade. Therefore, in this study, we analyzed the biological functions of coagulation-related genes (CRGs) in ccRCC patients using single-cell sequencing and TCGA data to establish the 5-CRGs based diagnostic signature and predictive signature for ccRCC. Univariate and multivariate Cox analyses suggested that prognostic signature could be an independent risk factor. Meanwhile, we applied CRGs for consistent clustering of ccRCC patients, and the two classes showed significant survival and genotype differences. The differences in individualized treatment between the two different subtypes were revealed by pathway enrichment analysis and immune cell infiltration analysis. In summary, we present the first systematic analysis of the significance of CRGs in the diagnosis, prognosis, and individualized treatment of ccRCC patients.

Efficacy of Mitomycin C Combined with Direct Vision Internal Urethrotomy for Urethral Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND: The high recurrence of a urethral stricture after direct vision internal urethrotomy (DVIU) has been a problem for years. Mitomycin C (MMC) is an excellent antifibrosis antigen that has been used in many fields, but its effect on a urethral stricture remains controversial. The purpose of this review was to investigate the effectiveness of MMC in reducing the recurrence rate of a urethral stricture after the first urethrotomy. METHODS: Common databases were searched for publications prior to November 30, 2020. Randomized controlled and cohort trials were all included. Recurrence and success rates after the first urethrotomy of the posterior urethra were the main outcomes. Revman 5.3 was used for statistical analysis. Two evaluation systems, the Cochrane risk of bias tool and the Newcastle Ottawa Scale, were used to examine the risk of bias for RCTs and all studies. The quality of evidence was assessed by the Grading of Recommendations, Assessment, Development, and Evaluation standard. RESULTS: Sixteen trials were included, the reporting quality of which was generally poor, and the evidence level was very low to moderate. The addition of MMC could significantly reduce the recurrence rate of urethral strictures (risk ratio [RR] = 0.42; 95% confidence interval [CI]: 0.26, 0.67; p = 0.0002; 9 trials; 550 participants). The results of the subgroup analysis suggested that the effect of MMC combined with DVIU was significant in short (≤2 cm) anterior urethral strictures (RR = 0.39; 95% CI: 0.20, 0.78; p = 0.008), >12-month follow-up (RR = 0.45; 95% CI: 0.26, 0.76; p = 0.003). It also increased the success rate of the first urethrotomy procedure for posterior urethral contracture (RR = 0.74; 95% CI: 0.65, 0.84; p < 0.00001; 7 trials; 342 participants). Low-dose local injection of MMC was the most commonly used method. CONCLUSION: MMC combined with DVIU is a promising way to reduce the long-term recurrence rate of a short-segment anterior urethral stricture. It also increases the success rate of the first urethrotomy of the posterior urethra. However, more high-quality randomized controlled trials are needed.

Identification of a claudin-low subtype in clear cell renal cell carcinoma with implications for the evaluation of clinical outcomes and treatment efficacy.

Background: In bladder and breast cancer, the claudin-low subtype is widely identified, revealing a distinct tumor microenvironment (TME) and immunological feature. Although we have previously identified individual claudin members as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC), the existence of an intrinsic claudin-low subtype and its interplay with TME and clinical outcomes remains unclear. Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA)- kidney clear cell carcinoma (KIRC) cohort and E-MTAB-1980 were derived as the training and validation cohorts, respectively. In addition, GSE40435, GSE53757, International Cancer Genome Consortium (ICGC) datasets, and RNA-sequencing data from local ccRCC patients were utilized as validation cohorts for claudin clustering based on silhouette scores. Using weighted correlation network analysis (WGCNA) and multiple machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), CoxBoost, and random forest, we constructed a claudin-TME related (CTR) risk signature. Furthermore, the CTR associated genomic characteristics, immunity, and treatment sensitivity were evaluated. Results: A claudin-low phenotype was identified and associated with an inferior survival and distinct TME and cancer immunity characteristics. Based on its interaction with TME, a risk signature was developed with robust prognostic prediction accuracy. Moreover, we found its association with a claudin-low, stem-like phenotype and advanced clinicopathological features. Intriguingly, it was also effective in kidney chromophobe and renal papillary cell carcinoma. The high CTR group exhibited genomic characteristics similar to those of claudin-low phenotype, including increased chromosomal instability (such as deletions at 9p) and risk genomic alterations (especially BAP1 and SETD2). In addition, a higher abundance of CD8 T cells and overexpression of immune checkpoints, such as LAG3, CTLA4 and PDCD1, were identified in the high CTR group. Notably, ccRCC patients with high CTR were potentially more sensitive to immune checkpoint inhibitors; their counterparts could have more clinical benefits when treated with antiangiogenic drugs, mTOR, or HIF inhibitors. Conclusion: We comprehensively evaluated the expression features of claudin genes and identified a claudin-low phenotype in ccRCC. In addition, its related signature could robustly predict the prognosis and provide guide for personalizing management strategies.

Clinical application of a double-modified sulfated bacterial cellulose scaffold material loaded with FGFR2-modified adipose-derived stem cells in urethral reconstruction.

BACKGROUND: Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. METHODS: First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. RESULTS: The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. CONCLUSIONS: Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Construction and validation of a ferroptosis-related long noncoding RNA signature in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear. METHODS: After sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients. RESULTS: The prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients. CONCLUSIONS: Our study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma.

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database. Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses. Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system. Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.

Structural Confinement and Energetic Matching Synergistic Effect toward a High-Energy Transfer Efficiency and a Significant Red Emission Enhancement in a Eu2+,Ln3+ Co-doped Sr9LiMn(PO4)7 Whitlockite Phosphor.

Despite an encouraging progress, Mn2+-activated red phosphors suffer from an insufficient emission intensity and a bad color purity. Thus, it is necessary to find a new strategy to realize a bright red emission through highly efficient Mn2+ sensitization. Herein, manipulating Eu2+-sensitized Sr9LiMn(PO4)7 (SLMP) composition by Ln3+ heterovalent substitution is proved to be able to substantially gain a tremendous Mn2+ emission enhancement and result in a dominant red Mn2+ emission. It is found that the emission enhancement ratio is proportional to the order of lanthanide contraction. Notably, Tb3+ doping realizes a 427-fold rise in the integrated emission intensity compared with the SLMP host, which is close to the theoretical maximum of 500. An underlying mechanism for Mn2+ red emission enhancement is proposed, which is attributed to a high-energy transfer probability from Eu2+ to Mn2+ via Ln3+-induced further structural confinement plus an energetic match effect. Meanwhile, homovalent (Ca2+) substitution could precisely tailor Mn2+ emitting color from orange-red to deep red. A warm-white LED device with a low color temperature of 3394 K, a high color-rendering index of 90.2, and suitable CIE coordinates of (0.403, 0.373) is fabricated using optimized phosphor SLMP:Eu2+, Tb3+. These results might reveal a new strategy to develop new red-emitting phosphors with a bright and highly purified red Mn2+ emission.

NFE2L3 promotes tumor progression and predicts a poor prognosis of bladder cancer.

The high incidence and vulnerability to recurrence of bladder cancer (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in BLCA has not been elucidated. In this study, NFE2L3 expression was significantly increased in BLCA samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival and metastasis-free survival in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited BLCA cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition in BLCA cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

Double-Modified Bacterial Cellulose/Soy Protein Isolate Composites by Laser Hole Forming and Selective Oxidation Used for Urethral Repair.

In this study, a double-modified bacterial cellulose/soybean protein isolate (DMBC/SPI), a new type of urethral tissue engineering scaffold with good biocompatibility, biodegradability, and cell-oriented growth, was prepared. Bacterial cellulose (BC) was physically and chemically modified by laser hole forming and selective oxidation to obtain the double-modified bacterial cellulose (DMBC). The soybean protein isolate (SPI) was compounded on DMBC to obtain DMBC/SPI with better biocompatibility. DMBC/SPI was used to repair the damaged urethra in rabbits. The results showed that DMBC/SPI was beneficial to heal the damaged urethra and did not cause a milder inflammatory response. The repaired urethra was smooth and continuous. DMBC/SPI has a good urethral repair effect and is expected to be used as a new urethral reconstruction material in clinical applications. In addition, FT-IR spectroscopy, SEM, static contact angle measurements, mechanical property investigation, and cell experiments were also performed to characterize the properties of DMBC/SPI composites.

A ureteral stricture disease score and classification system: correlation with upper urinary tract reconstructive surgery complexity.

BACKGROUND: To develop an original and standardized ureteral stricture disease (USD) score and classification system for quantifying ureter stricture characteristics, assessing complexity of the minimally invasive upper urinary tract reconstructive (UUTR) surgical procedure, formulating preoperative plans, and offering objective comparisons of surgical techniques between different institutions and surgeons. METHODS: We retrospectively reviewed a test set of 64 patients and a validation set of 170 patients who underwent minimally invasive UUTR surgery from January 2018 to January 2021. Three factors were selected to be included in the USD score and classification system: (I) stricture etiology (E, 1-2 points); (II) stricture segment (S, 0-3 points); and (III) length of stricture (L, 1-5 points). The UUTR surgery involves low-complex surgeries (cystoscopy with ureteral dilation and stent placement, ureteropyeloplasty, end to end repair, ureteral reimplantation) and high-complex surgeries (onlay repair (buccal mucosae, lingual mucosae, appendix mucosae), Boari flap repair and ileal ureter replacement). Estimated blood loss and operative time were used as surrogate indicators of surgical complexity. RESULTS: The interrater reliability of the USD score and classification system was 0.908. A linear relationship between the USD score and estimated blood loss was observed (rs =0.676, P<0.001). The USD score was also correlated with operative time (rs =0.638, P<0.001). A significant difference in USD scores was found between the high and low complexity surgery groups (4 vs. 7, P<0.001). Variability of UUTR surgery is based on USD classification system, but with regularity to conform to. CONCLUSIONS: The USD score and classification system is a concise, easily applicable, and validated scale to delineate the clinically significant features of ureter stricture that correlate with the complexity of the UUTR surgical procedure. The use of this score and classification system can facilitate preoperative plan and comparison of USD treatments in clinical practice and urological literature. Research with large sample is needed to further examine and modify the use of the system.

Comprehensive bioinformatics analyses of APOBECs family and identification of APOBEC3D as the unfavorable prognostic biomarker in clear cell renal cell carcinoma.

Purpose: At present, how early screening for ccRCC is still a thorny issue for urologists. Probing the mechanisms underlying the development of ccRCC and finding relevant prognostic biomarkers remains crucial. Therefore, we systematically analyzed the APOBEC family in this study and identified APOBEC3D as a prognostic biomarker. Methods: In this study, based on the TCGA database, we systematically assessed the expression and prognosis of the APOBEC family and analyzed potential bioinformatic pathways. We then constructed nomograms to predict the prognosis of ccRCC patients better. Afterward, we further focused on APOBEC3D in our data on ccRCC specimens. The APOBEC3D should be extensively studied in ccRCC in the future. Results: The results showed that the APOBEC family showed the most significant changes in expression in ccRCC. The pathway enrichment analysis showed that APOBEC3 family members mainly regulated cytidine and cytosine-related processes. Subsequently, the Cox regression was used to construct prognostic signature, and validated in ICGC and GEO databases. Next, a nomogram was created integrating clinical parameters showing good predictive performance. Finally, we screened for APOBEC3D and found in our clinical sample that patients with high expression of APOBEC3D had a worse prognosis. Conclusion: Based on these results, APOBEC family members play important roles in the development of ccRCC, and APOBEC3D could serve as the biomarker for predicting patient prognosis.

Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer.

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy. Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset. Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively. Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

Initial experiences with preoperative three-dimensional image reconstruction technology in laparoscopic pyeloplasty for ureteropelvic junction obstruction.

BACKGROUND: To explore the clinical value of three-dimensional image reconstruction technology (3DIT) on preoperative surgical planning and perioperative outcomes in laparoscopic pyeloplasty (LP). METHODS: Data of 25 patients with ureteropelvic junction obstruction (UPJO) admitted to our hospital from January 2018 to January 2019 was analyzed retrospectively. All patients underwent preoperative enhanced computed tomography (CT) scanning. In the 12 cases in the 3DIT group, preoperative planning involved the use of virtual operation and morphometry based on reconstruction of the CT data into three-dimensional (3D) images. Surgery in the other 13 cases was performed with traditional CT examination. Demographic, surgical outcome, and postoperative parameters were compared between these two groups. RESULTS: Reconstructed 3D images clearly showed the spatial structural relationships between the UPJO and surrounding blood vessels. In all 25 cases surgery was completed with no conversion to open surgery. Preoperative 3DIT analyses resulted in significant improvements to mean operation time (107.76 vs. 141.58 min, P=0.024), mean time of dissociating ureteropelvic junction (UPJ) (11.26 vs. 19.40 min, P=0.020), and mean estimated blood loss volume (23.84 vs. 49.16 mL, P=0.028). There were no statistically significant differences in perioperative complications, postoperative hospital stays or postoperative drainage time. CONCLUSIONS: 3DIT based on enhanced CT scans is of clinical value in the treatment of UPJO, as it can provide accurate anatomical information and reliable guidance for preoperative operation planning, and it facilitates image-guided LP.

High expression levels of DEF6 predicts a poor prognosis for patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant tumors and early detection contributes to a better prognosis. Finding new biomarkers for the diagnosis or treatment remains meaningful. DEF6 guanine nucleotide exchange factor (DEF6) is upregulated in ccRCC compared to normal controls, but the relationship between DEF6 expression and prognosis in ccRCC is unclear. Moreover, the potential biological functions of DEF6 in ccRCC remains unclear. In the present study, the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), TISIDB and the clinical database of the Peking University First Hospital were used to analyze DEF6 expression in ccRCC. Immunohistochemistry (IHC), western blotting and reverse transcription­quantitative PCR were used to examine the DEF6 protein and mRNA expression levels in cell lines and clinical samples. Subsequently, the Kaplan­Meier method and Cox regression analyses were used to determine the impact of DEF6 expression on the overall survival of patients alongside other clinical variables in both the TCGA database and the present clinical database. The results showed that both DEF6 mRNA and protein expression levels were upregulated in ccRCC compared to normal controls. The Kaplan­Meier survival analysis showed that patients with high DEF6 expression had poor prognoses from both the TCGA database and the present clinical database. Univariate survival analysis and multivariate survival analysis revealed that DEF6 could be an independent prognostic factor for ccRCC. Additionally, bioinformatics analysis indicated that differentially expressed genes related to DEF6 expression influenced ccRCC by regulating the tumor immune microenvironment. In conclusion, overexpression of DEF6 is significantly correlated with a poor prognosis for patients with ccRCC and DEF6 may influence the biological processes involved with ccRCC by regulating the immune microenvironment.