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Abstract Background Ribosomal RNA Processing 8 (RRP8) is a gene associated with RNA modification and has been implicated in the development of several types of tumors in recent research. Nevertheless, the biological importance of RRP8 in pan-cancer has not yet been thoroughly and comprehensively investigated. Methods In this study, we conducted an analysis of various public databases to investigate the biological functions of RRP8. Our analysis included examining its correlation with pan-cancer prognosis, heterogeneity, stemness, immune checkpoint genes, and immune cell infiltration. Furthermore, we utilized the GDSC and CTRP databases to assess the sensitivity of RRP8 to small molecule drugs. Results Our findings indicate that RRP8 exhibits differential expression between tumor and normal samples, particularly impacting the prognosis of various cancers such as Adrenocortical carcinoma (ACC) and Kidney Chromophobe (KICH). The expression of RRP8 is intricately linked to tumor heterogeneity and stemness markers. Additionally, RRP8 shows a positive correlation with the presence of tumor-infiltrating cells, with TP53 being the predominant mutated gene in these malignancies. Conclusion Our findings suggest that RRP8 may serve as a potential prognostic marker and therapeutic target in a variety of cancer types.

Abstract Background Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). Methods PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. Results TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. Conclusions In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.

Abstract Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Abstract Telemedicine has gained tremendous development during the COVID‐19 pandemic. With deblocking and opening, telemedicine accelerates the evolvution of the medical “snack community” and undermines the perception of medical students and staff, which promotes the incidence of psychosocial‐related disorders. Moreover, the inconsistent telemedicine adaptability between medical workers and patients aggravates the doctor–patient conflict due to the aging population and COVID‐19 squeal. Telemedicine is colliding with the national healthcare system, whose synchronization with conventional medical service is crucial to coordinate the relationship among medical payment, patient privacy and qualifications of clinicians. This study puts more emphasis on the double‐edged sword role of telemedicine in clinical practice and medical education during the COVID‐19 pandemic and beyond. Overall, while telemedicine has demonstrated its utility in health care throughout the COVID pandemic, it is pretty critical to continue evaluating the efficacy and limitations of telemedicine in order to maintain equal access to medical service and high‐quality medical education. A new concept as telemedicine‐medical “snack community”‐PHS ecosystem, where the psychological health education system and partners healthcare system with enough bandwidth, especially 5G technology, could optimize the effect of telemedicine on medical practice and education, is proposed.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Background: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. Aim: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. Methods: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. Results: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. Concludsion: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.

Abstract Background Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes. Methods We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0. Results Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance. Conclusions From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa.

Abstract Background Apolipoprotein F (APOF) has been less studied in cancers. Thus, we aimed to perform a pan-cancer analysis of the oncogenic and immunological effects of APOF on human cancer. Methods A standardized TCGA pan-cancer dataset was downloaded. Differential expression, clinical prognosis, genetic mutations, immune infiltration, epigenetic modifications, tumor stemness and heterogeneity were analyzed. We conducted all analyses through software R (version 3.6.3) and its suitable packages. Results Overall, we found that the common cancers differentially expressed between tumor and normal samples and prognostic-associated were BRCA, PRAD, KIRP, and LIHC in terms of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The pan-cancer Spearman analysis showed that the mRNA expression of APOF was negatively correlated with four tumor stemness indexes (DMPss, DNAss, ENHss, and EREG-METHss) with statistical significance for PRAD and was positively correlated for LIHC. In terms of BRCA and PRAD patients, we found negative correlation of APOF with TMB, MSI, neo, HRD and LOH. The mutation frequencies of BRCA and LIHC were 0.3%. APOF expression was negatively correlated with immune infiltration and positively correlated with tumor purity for PRAD patients. The mRNA expression of APOF was negatively associated with most TILs for LIHC, B cells, CD4+ T cells, neutrophils, macrophages and dendritic cells, but was positively associated with CD8+ T cells. Conclusions Our pan-cancer study offered a relatively comprehensive understanding of the roles of APOF on BRCA, PRAD, KIRP, and LIHC.

Abstract Current evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.

Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.

Abstract Background Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension. Methods Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages. Results We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p

Abstract In this study, we established a novel immunologic gene prognostic index (IGPI) to predict metastasis and provided new insights into tumor immune microenvironment (TIME) for PCa patients receiving radical radiotherapy. GBP2 and IGF1 were independent factors associated with metastasis-free survival. IGPI score was calculated based on GBP2 and IGF1 and this score was an independent risk factor for PCa patients undergoing radical radiotherapy. Patients with higher IGPI score were at higher risk of metastasis and biochemical recurrence, which were externally validated in the TCGA database and other GEO datasets. IGPI score had demonstrated moderate diagnostic ability of radiation resistance (AUC: 0.889). This score increased with the augment of Gleason score and T stage, as well as biochemical recurrence. Using EPIC, ESTIMATE and immunophenoscore (IPS) algorithms, cancer associated fibroblasts (CAFs), macrophages, stromal score, and estimate score were significantly higher in patients with metastasis group compared to their counterpart. Besides, for CAFs, macrophages, stromal score, and estimate score, patients with higher scores were at higher risk of metastasis, and the HRs were 3.65, 4.01, 4.27, and 3.78, respectively. IGPI score was highly positively associated with stromal score (coefficient: 0.39), immune score (coefficient: 0.43), estimate score (coefficient: 0.45), CAFs (coefficient: 0.42) and macrophages (coefficient: 0.42), while showing the opposite relationship with tumor purity (coefficient: − 0.45). In conclusion, we found that IGPI based on GBP2 and IGF1 might serve as a biomarker predicting metastasis for PCa patients. Besides, the current data further highlight the importance of CAFs in the metastatic process of PCa.

Abstract Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore that is required for proper chromosomal segregation and cell division. However, little is known regarding the probable mechanism of SKA3, particularly in terms of prostate cancer (PCA) progression. Multiple databases, including TCGA and GTEx, were utilized to examine the expression of SKA3 in PCA patients and to shed light on the clinical significance and potential mechanism of SKA3 in the onset and progression of PCA. The biological function of SKA3 was evaluated in vitro using RT–qPCR and the CCK8 assay. For statistical analysis, the R 3.6.3 software and its associated packages were utilized. SKA3 was shown to be considerably elevated in PCA patients and was linked to a shorter progress free interval (PFI). Furthermore, we discovered that SKA3 mRNA expression was higher in PCA cells than in normal cells, and inhibition of SKA3 could clearly reduce PCA cell proliferation using the CCK8 assay. Finally, SKA3 could be used as a predictive biomarker in PCA patients.

Background: Endothelial cells in the tumor microenvironment play an important role in the development of kidney renal clear cell carcinoma (KIRC). We wanted to further identify the function of endothelial cells in KIRC patients by integrating single-cell and bulk RNA sequencing data.Methods: Online databases provide the original data of this study. An endothelial-related prognostic index (ERPI) was constructed and validated by R version 3.6.3 and relative packages.Results: The ERPI consisted of three genes (CCND1, MALL, and VWF). Patients with high ERPI scores were significantly correlated with worse prognosis than those with low ERPI scores in the TCGA training group, TCGA test group, and GSE29609 group. A positive correlation was identified between the ERPI score and poor clinical features. The results of functional analysis indicated that ERPI was significantly associated with immune-related activities. We suggested that patients with high ERPI scores were more likely to benefit from immunotherapy based on the results of immune checkpoints, tumor microenvironment, stemness index, and TCIA, while patients with low ERPI scores were sensitive to gemcitabine, docetaxel, paclitaxel, axitinib, pazopanib, sorafenib, and temsirolimus according to the results of the “pRRophetic” algorithm. Therefore, this ERPI may help doctors choose the optimal treatment for patients with KIRC.Conclusion: By integrating single-cell and bulk RNA sequencing data from KIRC patients, we successfully identified the key genes from the perspective of endothelial cells in the tumor microenvironment and constructed ERPIs that had positive implications in precision medicine.

Background: We sought to determine whether leucine zipper protein 2 (LUZP2) could benefit men with prostate cancer (PCa) undergoing radical radiotherapy (RT) or prostatectomy (RP). Methods: Analysis was done on differentiating expression, clinical prognosis, co-expressed genes, immune infiltration, and epigenetic changes. All of our analyses were done using the R software (version 3.6.3) and the appropriate packages. Results: In terms of PCa, tumor samples expressed LUZP2 more than normal samples did. In the TCGA database and GSE116918, we found that LUZP2 was the only independent risk factor for PCa. The shared enriched pathways for patients undergoing RP or RT were cell-cell adhesion, regulation of filopodium assembly, and extracellular matrix containing collagen. With the exception of TNFRSF14, we discovered that LUZP2 was negatively correlated with 21 immune checkpoints in PCa patients receiving RT. We found a significant inverse relationship between LUZP2 expression and the tumor immune environment, which included B cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, in patients receiving RP or RT. Additionally, tumor purity was positively correlated with LUZP2. We found that the drug bortezomib may be susceptible to the LUZP2. DNA methylation was significantly associated with the mRNA expression of LUZP2 in PCa patients from the TCGA database, and LUZP2 methylation was positively correlated with immune cells. The proliferative activity of various PCa cells, which correlated to different stages of this disease, was also found to be significantly reduced by LUZP2 reduction, according to the results of our experimental work. Conclusions: We proposed a relatively comprehensive understanding of the roles of LUZP2 on PCa from the fresh perspective of senescence.

Abstract Objective To assess the effectiveness and safety of dorsal penile nerve block (DPNB) compared with tetracaine gel in analgesia for men undergoing rigid cystoscopy. Patients and methods This study was conducted as a prospective, randomized, double‐blind, placebo‐controlled, and single‐center trial. Men undergoing diagnostic rigid cystoscopy were randomly allocated into one of three groups (n = 86 each): (1) tetracaine gel group (DPNB with saline), (2) DPNB group (DPNB with ropivacaine + plain lubricant), and (3) combination group (DPNB with ropivacaine + tetracaine gel). The primary outcome was visual analog scale (VAS) for pain at cystoscopic inspection of the external sphincter. Results VAS (median [interquartile]) at inspection of the external sphincter was significantly lower in both DPNB and combination groups than that in tetracaine gel group (4 [3–6] and 4 [3–5] vs 6 [5–7], P < .0001), with a 33% reduction of median VAS. Overall pain level during procedure was significantly alleviated in the DPNB and combination groups with more stabilized HR and MAP when compared with tetracaine gel group. No adverse events were observed during DPNB including penile hematoma, erection, local anesthetic toxicosis or incompletion of cystoscopy. Conclusion Our study suggests analgesia provided by DPNB with or without tetracaine gel instilled is superior to that provided by tetracaine gel alone in men undergoing diagnostic rigid cystoscopy. Clinical Trials Registration ClinicalTrials.gov registration number: NCT02502487.

Background: Ferroptosis is a new type of programmed cell death which has been reported to be involved in the development of various cancers. In this study, we attempted to explore the possible links between ferroptosis and prostate cancer (PCa), and a novel ferroptosis-related gene prognostic index (FGPI) was constructed to predict biochemical recurrence (BCR) and radiation resistance for PCa patients undergoing radical radiotherapy (RRT). Moreover, the tumor immune microenvironment (TME) of PCa was analyzed.Methods: We merged four GEO datasets by removing batch effects. All analyses were conducted with R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish a network of transcriptional factor and competing endogenous RNA.Results: We established the FGPI based on ACSL3 and EPAS1. We observed that FGPI was an independent risk factor of BCR for PCa patients (HR: 3.03; 95% CI: 1.68–5.48), consistent with the result of internal validation (HR: 3.44; 95% CI: 1.68–7.05). Furthermore, FGPI showed high ability to identify radiation resistance (AUC: 0.963; 95% CI: 0.882–1.00). LncRNA PART1 was significantly associated with BCR and might modulate the mRNA expression of EPAS1 and ACSL3 through interactions with 60 miRNAs. Gene set enrichment analysis indicated that FGPI was enriched in epithelial–mesenchymal transition, allograft rejection, TGF beta signaling pathway, and ECM receptor interaction. Immune checkpoint and m6A analyses showed that PD-L2, CD96, and METTL14 were differentially expressed between BCR and no BCR groups, among which CD96 was significantly associated with BCR-free survival (HR: 1.79; 95% CI: 1.06–3.03). We observed that cancer-related fibroblasts (CAFs), macrophages, stromal score, immune score, estimate score, and tumor purity were differentially expressed between BCR and no BCR groups and closely related to BCR-free survival (HRs were 2.17, 1.79, 2.20, 1.93, 1.92, and 0.52 for cancer-related fibroblasts, macrophages, stromal score, immune score, estimate score, and tumor purity, respectively). Moreover, cancer-related fibroblasts (coefficient: 0.20), stromal score (coefficient: 0.14), immune score (coefficient: 0.14), estimate score (coefficient: 0.15), and tumor purity (coefficient: −0.15) were significantly related to FGPI, among which higher positive correlation between cancer-related fibroblasts and FGPI was observed.Conclusion: We found that FGPI based on ACSL3 and EPAS1 might be used to predict BCR and radiation resistance for PCa patients. CD96 and PD-L2 might be a possible target for drug action. Besides, we highlighted the importance of immune evasion in the process of BCR.

IntroductionTo compare the survival benefit of nephrectomy with or without lymph node dissection (LND) for non-metastatic, especially for high-risk renal cell carcinoma (RCC) patients by investigating different survival evaluation indicators.Evidence AcquisitionEligible studies were identified until September 2021, through common databases including PubMed, the Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) on RCC and LND without language restriction. Data analysis was performed through Stata software, version 16.0 (Stata Corp., College Station, TX, USA).Evidence Synthesis22 articles were included in this meta-analysis. For non-metastatic RCC, performing LND comitantly with nephrectomy did not change the overall survival (OS) of patients of all T stages [hazard ratio (HR)=1.10, 95%CI: 0.95-1.27] and also for T2+NxM0 patients (HR=0.88, 95%CI: 0.68-1.14) as well as for T3+NxM0 patients (HR=0.95, 95%CI: 0.61-1.50). At the same time, cumulative meta-analysis has shown that the survival benefit of LND has a significant declining trend since 1979. However, it is worth noting that the operation of LND presented as a risk factor for cancer specific survival (CSS) (HR=1.22, 95%CI: 1.05-1.43).ConclusionsLatest evidence indicated that LND might not be suitable for all non-metastatic RCC patients, especially in the current situation of various non-invasive examinations for judging lymph node metastasis and adjuvant treatments. On the contrary, excess LND could damage the survival of patients.Systematic Review RegistrationThis study is registered as PROSPERO CRD42021271124.

BackgroundCurrently, the impact of the circadian rhythm on the tumorigenesis and progression of prostate cancer (PCA) has yet to be understood. In this study, we first established a novel nomogram to predict PCA progression based on circadian clock (CIC)-related genes and provided insights into the tumor immune microenvironment.MethodsThe TCGA and Genecards databases were used to identify potential candidate genes. Lasso and Cox regression analyses were applied to develop a CIC-related gene signature. The tumor immune microenvironment was evaluated through appropriate statistical methods and the GSCALite database.ResultsTen genes were identified to construct a gene signature to predict progression probability for patients with PCA. Patients with high-risk scores were more prone to progress than those with low-risk scores (hazard ratio (HR): 4.11, 95% CI: 2.66-6.37; risk score cut-off: 1.194). CLOCK, PER (1, 2, 3), CRY2, NPAS2, RORA, and ARNTL showed a higher correlation with anti-oncogenes, while CSNK1D and CSNK1E presented a greater relationship with oncogenes. Overall, patients with higher risk scores showed lower mRNA expression of PER1, PER2, and CRY2 and higher expression of CSNK1E. In general, tumor samples presented higher infiltration levels of macrophages, T cells and myeloid dendritic cells than normal samples. In addition, tumor samples had higher immune scores, lower stroma scores and lower microenvironment scores than normal samples. Notably, patients with higher risk scores were associated with significantly lower levels of neutrophils, NK cells, T helper type 1, and mast cells. There was a positive correlation between the risk score and the tumor mutation burden (TMB) score, and patients with higher TMB scores were more prone to progress than those with lower TMB scores. Likewise, we observed similar results regarding the correlation between the microsatellite instability (MSI) score and the risk score and the impact of the MSI score on the progression-free interval. We observed that anti-oncogenes presented a significantly positive correlation with PD-L1, PD-L2, TIGIT and SIGLEC15, especially PD-L2.ConclusionWe identified ten prognosis-related genes as a promising tool for risk stratification in PCA patients from the fresh perspective of CIC.

Background: Bladder cancer is the second-ranked tumor of the genitourinary system. Transurethral resection of bladder tumor (TURBT) is currently the most important diagnosis and treatment method for non-muscular invasive bladder cancer (NMIBC). However, due to its high recurrence and progression rate, as well as high cost and inapplicability to some patients, intravesical chemoablation as an alternative to TURBT may be promising for NMIBC patients. However, there are very little data comparing its effectiveness, safety, best effective drug type, dosage selection, and cost with TURBT at present, which deserves further evaluation. The present study was designed in order to discuss which treatment is superior to another between chemoablation and TURBT in patients with NMIBC.Methods and Analysis: Databases including PubMed, MEDLINE, EMBASE, and Cochrane Library databases, as well as Chinese databases including CNKI (China national knowledge infrastructure), Wan Fang database, and Chinese Clinical Trial Registry, from August 1994 to the time when the official submission of this review was published was included in this review and screened by two reviewers (XS and DCF) independently. There were no language limitations. The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data was analyzed using RevMan and Stata software. The primary aims were the clinical effectiveness, including response rate, complete response OS, CSM, recurrence rate, time to recurrent, progression rate, and time to progression, among others. The secondary aims mainly included safety and tolerability, including costs, operation time, hospital stay, bleeding volume, and complications, among others.Study Registration: This study is registered as PROSPERO CRD42021271124.

Background: Tadalafil has been approved for the treatment of benign prostatic hyperplasia (BPH) for nearly 10 years. However, there are insufficient evidence-based studies of the efficacy and safety of tadalafil in treating lower urinary tract symptoms of BPH (LUTS/BPH).Objective: To evaluate the therapeutic effect and clinical safety of tadalafil monotherapy (5 mg once daily for 12 weeks) for LUTS/BPH.Methods: A total of 13 studies (15 randomized clinical trials [RCTs]) were extracted from the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science for the period up to July 2021. The quality of the included RCTs was evaluated independently by two authors, who, respectively, extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles. Conflicts were settled by a discussion with two-third of senior authors. All data analyses were conducted by the Review Manager, version 5.4.Results: Regarding efficacy, 12-week trials indicated that 5 mg once daily tadalafil showed a significantly lower and, consequently, better total International Prostate Symptom Score (IPSS) than the placebo did (mean difference [MD]: −1.97, 95% CI: −2.24 to −1.70; P < 0.00001). In addition, significant differences were found between the tadalafil regimen and the placebo in the IPSS voiding subscore (MD: −1.30, 95% CI: −1.48 to −1.11; P < 0.00001), the IPSS storage subscore (MD: −0.70, 95% CI: −0.82 to −0.58; P < 0.00001), the IPSS quality of life (MD: −0.29, 95% CI: −0.35 to −0.22; P < 0.00001), and BPH impact index (MD: −0.58, 95% CI: −0.76 to −0.40; P < 0.00001). The safety analysis did not show a significant difference in serious adverse events between the two groups (risk ratio: 1.27, 95% CI: 0.80–2.01; P = 0.31), although the adverse events occurred at a higher incidence in the tadalafil group than in the placebo.Conclusions: This study demonstrates that once daily 5 mg tadalafil is a potentially effective and safe treatment choice with excellent tolerability for patients with LUTS/BPH.Systematic Review Registration: Identifier (CRD42021228840).

Conservative treatment is closely associated with renal deterioration for patients with renal staghorn stones. It is well-recognized that percutaneous nephrolithotomy (PCNL) is recommended as the first-line treatment of renal stones larger than 2 cm due to its higher stone clearance and cost-effectiveness when compared with other treatment alternatives, such as shockwave lithotripsy and flexible ureteroscopy (FURS). Besides, our findings indicated that miniaturized PCNL could be served as an alternative to PCNL with a higher stone-free rate and a lower hemorrhage risk. Despite the higher cost-effectiveness of PCNL, the management of staghorn stones are still controversial in some special situations, such as a solitary kidney. Herein, we present a case with complex infectious stones of a right-sided solitary kidney, complaining of persistent pain in the right waist. The rarity of this case is that it is difficult to encounter these cotton-like staghorn stones which are clinically resistant to holmium laser lithotripsy, and the particularity is that the patient with solitary kidney failed to undergo PCNL. We found that the combination of intermittently high-frequency oscillation and flexible ureteroscopy forceps might contribute to treat the complex infectious stones in a patient with solitary kidney. Our surgical experience might be beneficial to such patients undergoing flexible ureteroscopy in clinical practice.

To identify the characteristics of patients with sepsis or acute pyelonephritis (APN) combined with ureteral calculi and to analyze the risk factors in its causation. Methods: We included patients with sepsis or APN caused by ureteral calculi who received treatment in the United States from January 2003 to December 2017 using the Optum® deidentified Clinformatics® Datamart. Demographic factors and risk factors for the receipt of sepsis or APN were subsequently analyzed for statistical significance. Results: Of 467,502 urinary stone patients, age-matched multivariate analysis revealed that a history of urinary tract infection (OR 11.31, 95% CI 10.68–11.99, p < 0.0001) and female gender (OR 2.73, 95% CI 2.62–2.84, p < 0.0001) were significantly related to an increased risk of sepsis or APN. Conversely, a previous past medical history of urolithiasis (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) and cancer (OR 0.91, 95% CI 0.87–0.95, p < 0.0001) were associated with a decreased risk of sepsis or APN. With regards to comorbidities, when more than one comorbidity was present, there was an additive effect with higher OR point estimates, rising to 11.31 (10.68–11.99) when three or more comorbidities present. History of urinary tract infection and female gender are risk factors for sepsis or APN in patients with ureteral calculi. Conclusions: This large national cohort reveals the characteristics of sepsis or APN combined with ureteral stone and provides an important baseline for the treatment of urolithiasis in the future.

Background: We aimed to explore the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in prostate cancer (PCa) patients and provide insights into the tumor immune microenvironment (TME) for those patients undergoing radical radiotherapy. Methods: We performed all analyses using R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish network of competing endogenous RNAs (ceRNAs). Results: Downregulation of ADLH2 was significantly associated with higher risk of BCR-free survival (HR: 0.40, 95%CI: 0.24–0.68, p = 0.001) and metastasis-free survival (HR: 0.21, 95%CI: 0.09–0.49, p = 0.002). Additionally, ALDH2 repression contributed to significantly shorter BCR-free survival in the TCGA database (HR: 0.55, 95%CI: 0.33–0.93, p = 0.027). For immune checkpoints, patients that expressed a higher level of CD96 had a higher risk of BCR than their counterparts (HR: 1.79, 95%CI: 1.06–3.03, p = 0.032), as well as NRP1 (HR: 2.18, 95%CI: 1.29–3.69, p = 0.005). In terms of the TME parameters, the spearman analysis showed that ALDH was positively associated with B cells (r: 0.13), CD8+ T cells (r: 0.19), neutrophils (r: 0.13), and macrophages (r: 0.17). Patients with higher score of neutrophils (HR: 1.75, 95%CI: 1.03–2.95, p = 0.038), immune score (HR: 1.92, 95%CI: 1.14–3.25, p = 0.017), stromal score (HR: 2.52, 95%CI: 1.49–4.26, p = 0.001), and estimate score (HR: 1.81, 95%CI: 1.07–3.06, p = 0.028) had higher risk of BCR than their counterparts. Our ceRNA network found that PART1 might regulate the expression of ALDH via has-miR-578 and has-miR-6833-3p. Besides, PHA-793887, PI-103, and piperlongumine had better correlations with ALDH2. Conclusions: We found that ALDH2 might serve as a potential biomarker predicting biochemical recurrence for PCa patients.

Background: A systematic review and meta-analysis was conducted to explore the effect of local treatment (LT) on overall survival (OS) and cancer-specific mortality (CSM) for patients diagnosed with M1c prostate cancer (PCa).Methods: PubMed, Web of Science, Embase, EBSCO, and Cochrane library databases (updated November 2020) were searched for studies assessing the effect of LT on patients with M1c Pca. The search strategy and study selection process was managed according to the PRISMA statement.Results: Four cohort respective studies were identified for satisfying the inclusion criteria. Our results indicated that LT significantly improved CSM (HR = 0.36, 95% CI = 0.22–0.60; P < 0.0001) and OS (HR = 0.42, 95% CI = 0.24–0.77; P = 0.004). Subgroup analysis showed that radical prostatectomy (RP) and radiation therapy (RT) including brachytherapy (BT), conformal radiation therapy (CRT), and intensity modulated radiation (IMRT) had a significant benefit on cutting down the CSM of M1c PCa patients (HR = 0.27, 95% CI = 0.13–0.56; P = 0.0005 and HR = 0.42, 95% CI = 0.20–0.89; P = 0.02). In addition, RP had improved the OS for patients (HR = 0.33, 95% CI = 0.15–0.73; P = 0.008). There was no difference of OS in patients that underwent RT (HR = 0.58, 95% CI = 0.24–1.40; P = 0.23). No significant heterogeneity was among the results, indicating consistency in the study.Conclusions: Present meta-analysis indicates that LT for M1c PCa correlated with decreased CSM and enhanced OS. The survival benefit of RP was successfully confirmed and the advantage of RT seemed to be associated with the tumor burden and method of RT.

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) for investigating the effect of dietary treatment and fluid intake on the prevention of recurrent calcium stones and changes in urine composition. PubMed, Web of Science, Embase, EBSCO, and Cochrane Library databases (updated November 2020) were searched for studies with the following keywords: diet, fluid, recurrent, prevention, randomized controlled trials, and nephrolithiasis. The search strategy and study selection process was conducted by following the PRISMA statement. Six RCTs were identified for satisfying the inclusion criteria and enrolled in this meta-analysis. Our result showed that low protein with or without high fiber diet intervention does not decrease the recurrence of stone upon comparing with control groups (RR = 2.32, 95% CI = 0.42-12.85; P = 0.34) with significant heterogeneity among the studies (I2 = 81%, P = 0.02). But normal-calcium, low protein, low-salt diet had recurrences did reduced the recurrence compared to normal-calcium diet. And the fluid intake has a positive effect on prevention of recurrent stone formation (RR = 0.39, 95% CI = 0.19-0.80; P = 0.01) with insignificant heterogeneity among the studies (I2 = 9%, P = 0.30). The different components of urine at baseline were reported in four studies. Upon reviewing the low protein with or without high fiber dietary therapy groups, it was found that there were no obvious changes in the 24-hour urine sodium, calcium, citrate, urea, and sulfate. In conclusion, our study shows that the only low protein with or without fiber does not affect recurrence, but low Na, normal Ca diet has a marked effect on reducing recurrence of calcium stone. And fluid intake shows a significant reduction in the recurrence of calcium stone.

A systematic review and meta-analysis was conducted to explore the effect of a eutectic mixture of local anaesthetics (EMLA) on pain reduction during extracorporeal shockwave lithotripsy (ESWL). PubMed, Web of Science, Embase, EBSCO, and Cochrane library databases (updated March 2020) were searched for randomised controlled trials (RCTs) assessing the effect of EMLA for patients that underwent ESWL. The search strategy and study selection process were managed according to the PRISMA statement. Six RCTs were included in the meta-analysis. Overall, the results indicated that EMLA significantly reduced pain compared to the control group (RR = -2.98, 95% CI = -5.82 to -0.13, P = 0.04) with a heterogeneity of I2 = 57% (P = 0.04). Subgroup analysis showed that EMLA did not significantly reduce pain when the patients took an analgesic premedication (RR = -1.46, 95% CI = -5.89 to 2.98, P = 0.52) with a heterogeneity of I2 = 38% (P = 0.52). Conversely, studies without premedication showed a significant pain relief effect (RR = -4.08, 95% CI = -7.36 to -0.65, P = -0.80) with a heterogeneity of I2 = 48% (P = 0.14). Most studies showed there was no difference in the patient's need for analgesics. EMLA was effective for reducing pain during EWSL. However, this analgesic effect was limited and did not reduce the need for analgesics.

Background: The purpose of this study was to explore the ability of nonpharmacologic adjuvant interventions to alleviate pain in male patients during flexible cystoscopy (FC) under local anesthesia. Methods: Electronic databases including PubMed, the Cochrane Library, and Embase were searched to identify eligible clinical trials from inception to 31 December 2020, with no language restrictions. Two independent reviewers used Cochrane Collaboration tools to assess the selection criteria, methodological rigor and risk of bias. Statistical analyses were performed using STATA 14.2. Results: In total, 717 studies were initially identified, and fourteen randomized controlled trials were ultimately included. We observed that patients who underwent FC with higher irrigation pressures had significantly lower pain scores on the visual analog scale than their counterparts with lower irrigation pressure during FC (weight mean difference (WMD): −1.43; 95% confidence interval (CI): −1.72 to −1.14) with no between-study heterogeneity (p = 0.661). There were no significant differences in pain between immediate or delayed FC groups under the same local anesthetic (standard mean difference (SMD): −0.19; 95% CI: −0.39 to 0.01). A pooled analysis of three studies including 340 male patients showed that men who observed the cystoscopy on the monitor had significantly lower pain ratings compared to those who did not view the operation on the monitor (SMD: −0.64; 95% CI: −1.14 to −0.15). Two studies, including a total of 272 patients, assessed the influence of listening to music on pain and anxiety in male patients during FC. Our meta-analysis found that music significantly improved patient pain (WMD: −0.92; 95% CI: −1.29 to −0.54). Hand-holding and urination during FC also relieved pain and anxiety in male patients undergoing FC. Conclusions: We observed that elevated irrigation pressure, real-time cystoscopy visualization, and music therapy alleviated pain in male patients undergoing FC. Well-designed trials are needed to confirm our findings.

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pancancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large Bcell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention. [ABSTRACT FROM AUTHOR]

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients. [ABSTRACT FROM AUTHOR]