Household air pollution and urinary incontinence symptoms among older adults in LASI: a large-scale population-based study.

BACKGROUND: The effects of household air pollution on urinary incontinence (UI) symptoms and stress urinary incontinence (SUI) symptoms have not been studied. This study seeks to investigate the correlation between household air pollution and UI/SUI symptoms among middle-aged and elderly adults in India. METHODS: We employed data derived from individuals aged 45 years and older who participated in the inaugural wave (2017-2018) of the Longitudinal Aging Study in India (LASI). The assessment of household air pollution exposure and the occurrence of UI/SUI symptoms relied on self-reported data. The analytical approach adopted was cross-sectional in nature and encompassed a cohort of 64,398 participants. To explore relationships, we utilized multivariate logistic regression analysis, incorporating subgroup analysis and interaction tests. RESULTS: 1,671 (2.59%) participants reported UI symptoms and 4,862 (7.55%) participants reported SUI symptoms. Also, the prevalence of UI/SUI symptoms is much higher among middle-aged and elderly adults who use solid polluting fuels (UI: 51.23% vs. 48.77%; SUI: 54.50% vs. 45.50%). The results revealed a noteworthy correlation between household air pollution and the probability of experiencing UI/SUI symptoms, persisting even after adjusting for all conceivable confounding variables (UI: OR = 1.552, 95% CI: 1.377-1.749, p < 0.00001; SUI: OR: 1.459, 95% CI: 1.357-1.568, p < 0.00001). Moreover, significant interaction effects were discerned for age, education level, tobacco consumption, alcohol consumption, and physical activity (p for interaction < 0.05). CONCLUSIONS: The results of our study indicate that the utilization of solid fuels in the home increases the likelihood of developing urinary incontinence and stress urinary incontinence. As a result, we argue that there is an immediate need to reform the composition of cooking fuel and raise public awareness about the adverse effects of air pollution in the home.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Effect of vaginal energy-based treatment on female stress urinary incontinence: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy and safety of vaginal energy-based therapies in treating female SUI. METHODS: The PubMed, EMBASE, Web of Science, and Scopus databases were searched up to September 2022 to identify RCTs comparing energy-based therapies with placebo intervention in treating female SUI. The primary outcome was International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score. Secondary outcomes included the 1-h pad test and cure rate. RESULTS: A total of 577 patients from 6 studies were included in the meta-analysis. Energy-based therapies did not significantly improve the ICIQ-SF score at all visits (≤ 1 month: SMD, -0.39; 95% CI - 0.80 to 0.03; P = 0.07; 3 months: SMD, - 1.32; 95% CI - 4.07 to 1.43; P = 0.35; 6 months: SMD, - 0.39; 95% CI - 0.91 to 0.12; P = 0.14). The subgroup analysis showed that there was no significant improvement in ICIQ-SF score in the CO2 laser group compared to the placebo group at all visits (≤ 1 month: SMD, - 0.13; 95% CI - 0.59 to 0.34; P = 0.59; 3 months: SMD, - 1.50; 95% CI - 3.91 to 0.92; P = 0.22; 6 months: SMD, 0.13; 95% CI - 0.47 to 0.72; P = 0.67). Meta-analysis was not performed in Er: YAG laser and radiofrequency therapy due to insufficient trials. CONCLUSION: Based on the limited clinical evidence, our meta-analysis showed no prior efficacy of energy-based therapy over placebo intervention. However, the results of this meta-analysis should be taken with caution due to the limited amount of available evidence and the heterogeneity among the included studies. PROSPERO REGISTRATION NUMBER: CRD42022360471.

Association between preoperative serum albumin and prognosis in patients with adrenocortical carcinoma after primary resection: a retrospective study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. Given the limited treatment options, prognostic assessment of ACC is increasingly crucial. In this study, we aim to assess the correlation between preoperative serum albumin and prognosis in patients with ACC after primary resection. METHODS: We retrospectively collected and reviewed medical information about 71 ACC patients who underwent primary resection. Survival analysis was performed by Kaplan-Meier analysis with log-rank test or Breslow test. Receiver operating characteristic (ROC) curve and Jordan index was generated to explore optimal cut-off value of albumin. Univariate and multivariate analysis was conducted using Cox's hazards model. Statistical significance was defined as P < 0.05. RESULTS: Among included patients, 33 patients (46.5%) relapsed at the end of follow-up, while 39 patients (54.9%) died. The median overall survival (OS) of included patients was 17 (range 1-104) months, and median recurrence-free survival (RFS) was 10 (range 0-104) months. In univariate analysis, the albumin was significantly associated with OS (HR:0.491, 95% CI: 0.260-0.930, P = 0.029) and RFS (HR: 0.383, 95% CI: 0.192-0.766, P = 0.007). In multivariate analysis, serum albumin as an independent prognostic factor of OS was confirmed (HR: 0.351, 95% CI: 0.126-0.982, P = 0.046). CONCLUSIONS: Preoperative albumin might be a significant prognostic factor for ACC patients after primary resection. This result may be useful for risk stratification and management of this rare malignancy.

Comparative effectiveness and safety of intravesical instillation treatment of interstitial cystitis/bladder pain syndrome: a systematic review and network meta-analysis of randomized controlled trials.

INTRODUCTION AND HYPOTHESIS: A large variety of agents are available for intravesical instillation treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). The purpose of the study was to compare the efficacy and safety of those agents. METHODS: PubMed, the Cochrane Library, and Embase were searched from database inception to February 2020 for randomized controlled trials. The language of publication was limited in English. Population, intervention, comparison, outcome, and study design was used to assess the eligible studies for inclusion and the Cochrane Collaboration's risk of bias tool was used to assess the methodological quality of the studies included. The primary outcome was O'Leary-Sant Interstitial Cystitis Problem Index (ICPI) and O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) improvement. RESULTS: Eleven randomized controlled trials covering 8 agents with 902 patients were enrolled. According to the results of the ICPI and ICSI, 0.1 µM resiniferatoxin was more effective than other therapies. Combination therapy of hyaluronic acid and chondroitin sulphate ranked second in ICSI, third in ICPI, and first in the visual analog scale (VAS). Among regimens included for complication comparison, chondroitin sulphate was safer than other agents, with a probability of 78.5%. CONCLUSIONS: Resiniferatoxin (0.1 µM) is more effective at ICPI and ICSI improvement than other agents. More well-designed randomized controlled trials with a large sample size directly comparing the efficacy and safety of those agents are in need in the future to confirm our findings.

Transurethral resection of ejaculatory duct combined with seminal vesiculoscopy for management of persistent or recurrent hemospermia in men with ejaculatory duct obstruction.

BACKGROUND: Persistent or recurrent haemospermia often occurs in individuals with ejaculatory duct obstruction (EDO). This study aimed to evaluate the efficacy and safety of transurethral resection of the ejaculatory duct (TURED) combined with seminal vesiculoscopy in treating persistent or recurrent haemospermia in men with EDO. METHODS: From June 2014 to March 2018, 103 consecutive patients with EDO who underwent TURED combined with seminal vesiculoscopy for persistent or recurrent haemospermia at the Department of Urology of West China Hospital were enrolled into this retrospective study. The patients were evaluated mainly by detailed history-taking and performing semen analysis, transrectal ultrasonography, and magnetic resonance imaging. RESULTS: Among the 103 patients, 79 (76.70%) had cysts of the lower male genitourinary tract; 63 (61.17%) had blood clots; and 32 (31.07%) had calculi in the seminal vesicle and/or prostatic utricle. The duration of postoperative follow-up was 12 months, and the symptoms of haemospermia disappeared in 96 (93.20%) patients. There was no significant difference in the semen PH and sperm count before and after surgery; however, the ejaculate volume and sperm motility significantly improved postoperatively. Except for two cases of acute urinary retention and one case of watery ejaculate after surgery, no severe postoperative complications, including epididymitis, urethral stricture, urinary incontinence, retrograde ejaculation, or rectal injury, were observed. CONCLUSION: TURED combined with seminal vesiculoscopy is a suitable method for the diagnosis and treatment of persistent or recurrent haemospermia in men with EDO.

The relationships between bariatric surgery and sexual function: current evidence based medicine.

BACKGROUND: Controversy remains despite several studies have discussed the role of bariatric surgery in improving male's sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male's erectile function. METHODS: PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome. RESULTS: Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12-6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19-3.94; orgasmic function: MD = 0.50, 95%CI 0.60-0.94; overall satisfaction: MD = 1.67, 95% CI 0.78-2.56; sexual desire: MD = 1.27, 95% CI 0.61-1.93; total erectile function: MD = 7.21, 95% CI 4.33-10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39-2.67; ejaculation: MD = 1.40, 95% CI 1.28-1.51; desire: MD =1.40, 95% CI 1.32-1.49; problem assessment: MD = 2.20, 95% CI 2.06-2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60-0.76) in obese individuals after bariatric surgery. CONCLUSIONS: This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males's sexual function for obese individuals.

The association between variants in the CFTR gene and nonobstructive male infertility: A meta-analysis.

The association of genetic variants and congenital bilateral absence of the vas deferens (CBAVD) has been well acknowledged. By contrast, the link between nonobstructive azoospermia (NOA) or oligospermia and alterations in the cystic fibrosis transmembrane conductive regulator (CFTR) remains inconclusive. To clarify the problem, a meta-analysis was performed out after systematically searching Pubmed, Web of Science, Embase and the Chinese national knowledge infrastructure (CNKI) database. As we know, the ∆F508 and IVS8-5T gene mutations are the most studied genetic variants in CFTR gene. We reviewed the data from male patients who underwent the aforementioned genetic test. Our study revealed that the IVS8-5T mutation may be positively associated with the risk of nonobstructive male infertility (odds ratio (OR) 1.69; 95% CI: 1.12-2.55). This association strengthened when concerning NOA (OR: 2.62; 95% CI: 1.49-4.61). However, the ∆F508 mutation seemed to be a smaller contributing factor to this risk (OR: 1.63; 95% CI: 0.86-3.08). Our study aims to clarify the association between the ∆F508 and IVS8-5T gene mutations and nonobstructive male infertility. Therefore, screening for the IVS8-5T mutation in the CFTR gene may be recommended for men with NOA or severe oligozoospermia seeking assisted reproductive technology (ART).

Analysis of key genes and micro-RNA-mRNA regulatory networks in women with ulcerative interstitial cystitis/pain bladder syndrome.

INTRODUCTION AND HYPOTHESIS: This aim of this study was to better understand ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS) at the molecular level and provide new clues related to diagnosis and treatment. METHODS: The microarray data set GSE11783, including the mRNA and miRNA profiles of bladder tissue obtained at cystoscopic biopsy from patients with ulcerative IC/PBS (presence of at least one Hunner's ulcer) and normal controls, was downloaded from the GEO (Gene Expression Omnibus) database (National Center for Biotechnology Information). These were evaluated using Greenspring GX and Ingenuity Pathway Analysis (IPA) software. The differentially expressed genes (DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, the DEGs were subjected to functional analysis, and a protein-protein interaction (PPI) network was constructed. Finally, the miRNA-mRNA regulatory network was visualized using Cystoscope software. RESULTS: Four DEMs and 1521 DEGs were identified between the ulcerative IC/PBS and control groups. The PPI network of the DEGs was constructed by STRING, which was composed of 393 nodes and 1039 edges, including 221 upregulated genes and 172 downregulated genes. Moreover, 27 genes in the PPI network were identified as hub genes in the IC/PBS group, e.g., PNOC, SSTR1, FPR3, GPR18 and APLNR. Subsequently, 27 clusters were selected from the PPI network using MCODE. It was shown that the most significant cluster consisted of 22 nodes and 231 edges. Moreover, miR-21 was the most significantly upregulated miRNA and was predicted to target one upregulated gene (RASGRP1) and two downregulated genes (KLF5 and SC5D). CONCLUSIONS: The results of this data mining and integration provide further information on the possible molecular basis of IC/PBS pathogenesis as well as potential biomarkers and therapeutic targets for ulcerative IC/PBS diagnosis and treatment.

Aryl hydrocarbon receptor rs2066853 gene polymorphisms and male infertility risk: a meta-analysis.

To evaluate the relationship between the aryl hydrocarbon receptor (AHR) rs2066853 gene polymorphism and the risk of male infertility. PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant case-control studies up to 31 July 2019. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations. Finally, seven case-control studies involving 1247 cases and 1762 controls were included in this meta-analysis. The pooled results showed that there was no significant association between AHR rs2066853 gene polymorphism and male infertility risk (A vs. G: OR = 1.08, 95% CI = 0.83-1.39; AA vs. GG: OR = 1.16, 95% CI = 0.65-2.04; AA vs. GA + GG: OR = 1.17, 95% CI = 0.66-2.07; AA + GA vs. GG: OR = 0.99, 95% CI = 0.85-1.15). Subgroup analysis by ethnicity showed the same result. However, significant association was found between AHR rs2066853 gene polymorphism and male infertility risk in oligoasthenotspermia (A vs. G: OR = 2.52, 95% CI = 1.72-3.70). In conclusion, our meta-analysis indicated that AHR rs2066853 gene polymorphism might be associated with an increased susceptibility to oligoasthenotspermia.

TP53 gene Arg72Pro polymorphism and male infertility risk: A meta-analysis.

To evaluate the association between TP53 codon72 polymorphism and male infertility risk. We conducted a search on Medline, Embase, Web of Science and CNKI up to April 30, 2017. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of the association. Seven studies including 1,818 cases and 2,278 controls met the inclusion criteria. The pooled results indicated that no significant association was observed between TP53 codon72 polymorphism and male infertility risk (G versus C: OR = 1.11, 95%CI = 0.94-1.32; GG versus CC: OR = 1.26, 95%CI = 0.90-1.78; GG versus GC+CC: OR = 1.16, 95%CI = 0.90-1.49; GG+GC versus CC: OR = 1.15, 95%CI = 0.88-1.49). In the subgroup analysis by ethnicity, significant association was observed between TP53 codon72 polymorphism and male infertility risk in non-Chinese (G versus C: OR = 1.47, 95%CI = 1.14-1.89), but not in Chinese population (G versus C: OR = 1.03, 95%CI = 0.87-1.22). In conclusion, this study suggested that TP53 codon72 polymorphism might be associated with an increased susceptibility to male infertility in non-Chinese population, but not in Chinese population. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.

The SPO11-C631T gene polymorphism and male infertility risk: a meta-analysis.

To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.

A Joint Time-Frequency Domain Transformer for multivariate time series forecasting.

In order to enhance the performance of Transformer models for long-term multivariate forecasting while minimizing computational demands, this paper introduces the Joint Time-Frequency Domain Transformer (JTFT). JTFT combines time and frequency domain representations to make predictions. The frequency domain representation efficiently extracts multi-scale dependencies while maintaining sparsity by utilizing a small number of learnable frequencies. Simultaneously, the time domain (TD) representation is derived from a fixed number of the most recent data points, strengthening the modeling of local relationships and mitigating the effects of non-stationarity. Importantly, the length of the representation remains independent of the input sequence length, enabling JTFT to achieve linear computational complexity. Furthermore, a low-rank attention layer is proposed to efficiently capture cross-dimensional dependencies, thus preventing performance degradation resulting from the entanglement of temporal and channel-wise modeling. Experimental results on eight real-world datasets demonstrate that JTFT outperforms state-of-the-art baselines in predictive performance.

Roles of reactive oxygen species in inflammation and cancer.

Reactive oxygen species (ROS) constitute a spectrum of oxygenic metabolites crucial in modulating pathological organism functions. Disruptions in ROS equilibrium span various diseases, and current insights suggest a dual role for ROS in tumorigenesis and the immune response within cancer. This review rigorously examines ROS production and its role in normal cells, elucidating the subsequent regulatory network in inflammation and cancer. Comprehensive synthesis details the documented impacts of ROS on diverse immune cells. Exploring the intricate relationship between ROS and cancer immunity, we highlight its influence on existing immunotherapies, including immune checkpoint blockade, chimeric antigen receptors, and cancer vaccines. Additionally, we underscore the promising prospects of utilizing ROS and targeting ROS modulators as novel immunotherapeutic interventions for cancer. This review discusses the complex interplay between ROS, inflammation, and tumorigenesis, emphasizing the multifaceted functions of ROS in both physiological and pathological conditions. It also underscores the potential implications of ROS in cancer immunotherapy and suggests future research directions, including the development of targeted therapies and precision oncology approaches. In summary, this review emphasizes the significance of understanding ROS-mediated mechanisms for advancing cancer therapy and developing personalized treatments.

Identification of the ferroptosis regulator HELLS with prognostic value for adrenocortical carcinoma based on integrated analysis and experimental validation.

Background: For adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high rate of mortality and recurrence, it is difficult for clinicians to predict overall survival and select the most effective treatment. Targeting ferroptosis, a form of cell death, has been reported to be a promising therapeutic strategy for ACC; however, the core ferroptosis regulator and its prognostic value in ACC remain unknown. Methods: RNA sequencing data and clinical information were downloaded from public databases. Differentially expressed gene and survival analyses were performed to identify candidate ferroptosis regulators. A multivariate Cox regression model was used to construct a gene signature, and a nomogram was constructed to predict the overall survival of patients with ACC. Gene set variation analysis (GSVA) was used to identify underlying aberrant pathways and the relative immune cell infiltration levels of each ACC sample. Immunohistochemistry staining was performed in formalin-fixed paraffin-embedded tumor tissue sections. Results: Ultimately, 23 differentially expressed ferroptosis regulators were identified between normal adrenal gland and ACC tissues, and 50 ferroptosis regulators were related to prognosis, with 13 ferroptosis regulators being simultaneously found to satisfy the differential expression and prognostic value. According to the multivariate Cox regression model, a ferroptosis regulator signature was constructed from 3 genes in The Cancer Genome Atlas (TCGA; hazard ratio =9.01; P=1.39×10-10), and the area under the curve (AUC) values of 3-, 5-, 8-year overall survival were 0.924, 0.906, and 0.866, respectively. The survival analysis and the receiver operating characteristic (ROC) analysis validated the prognostic value of the ferroptosis regulator signature in 3 validation datasets. Moreover, metabolism-, E2F-, MYC-, and G2/M checkpoint-related pathways and aberrant immune cell infiltration levels were identified as being responsible for the different prognosis of risk groups in ACC. HELLS was found to be a significantly differentially expressed ferroptosis-suppressor gene with a prognostic value in ACC and to be highly associated with immune cell infiltration levels and multiple biological functions. Conclusions: A ferroptosis regulator signature showed promising power for predicting the prognosis of ACC, and HELLS was identified as a hub ferroptosis regulator in the initiation and progression of ACC.

Current management strategy of treating patients with erectile dysfunction after radical prostatectomy: a systematic review and meta-analysis.

The aim of this study is to present a summary of current evidence concerning the various treatments in the management of penile rehabilitation after radical prostatectomy (RP) and provide recommendations for future research. Randomized controlled trials (RCTs) were identified from electronic databases including PubMed, the Cochrane Library, Embase, and Web of Science from inception through March 2020 with no limitation to language. Comparable data from each study were combined in a meta-analysis where possible, otherwise data were synthesized narratively. The data analysis was completed by Review Manager version 5.3. A total of 39 RCTs were included in this study. At present, phosphodiesterase type 5 inhibitors (PDE5is) remain the first-line treatment for patients with erectile dysfunction (ED) after RP. Compared with the placebo group, patients in regular PDE5is group (mean difference (MD): 0.76; 95% confidence interval (CI): 1.69-4.44; p < 0.0001) and on demand group (MD: 3.92; 95% CI: 2.95-4.88; p < 0.00001) had a significantly higher mean Erectile Function domain of the International Index of Erectile Function (IIEF-EF) scores within 3 months after RP. As for the proportion of IIEF-EF ≥ 22, patients in regular PDE5is group and on demand PDE5is group had significantly higher proportion than those in placebo group 6 months after RP, and the odds ratios were 1.87 (95% CI: 1.32-2.66; p = 0.0005) and 2.17 (95% CI: 1.20-3.93; p = 0.01), respectively. No significant difference was observed between regular PDE5is group and on demand group regardless of mean IIEF-EF score or the proportion of IIEF-EF ≥ 22. Intracorporeal injection therapy seemed to have similar efficacy to PDE5is. The International Index of Erectile Function-5 items (IIEF-5) scores were significantly higher in vacuum constriction devices group than control group at 6-9 months after RP (MD: 6.70, 95% CI: 2.30-11.10, p = 0.003) with great between-study heterogeneity (p = 0.06, I2 = 72%). The other therapeutics including low-intensity extracorporeal shockwave therapy, statin therapy, psychotherapy interventions, and pelvic floor muscle training plus electrical stimulation showed certain improvement on erectile function. We found that the combination therapy showed certain advantages over monotherapy. Currently, PDE5is-based combination therapy remains the mainstream treatment for ED after RP. Intracorporeal injection therapy and vacuum therapy could be served as alternative treatments if PDE5is are ineffective and contraindicated.

Macrophage-Specific Cathepsin as a Marker Correlated with Prognosis and Tumor Microenvironmental Characteristics of Clear Cell Renal Cell Carcinoma.

Background: Cathepsin Z (CTSZ) is a cathepsin family member that plays a dual role in the adhesion and migration of immune and tumor cells. Methods: The expression pattern of CTSZ in clear cell renal cell carcinoma (ccRCC) was observed by immunohistochemistry and validated by using double-labeling immunofluorescence. Publicly available single-cell sequencing data was used to further define the cell type-specific CTSZ expression in ccRCC. Methylation modification, immune infiltration, and tumor-related signaling enrichment analyses involving CTSZ were performed using multi-omics data. Data from two independent cohorts of anti-programmed death-1 (PD-1) therapeutic clinical trials were used to investigate correlations between CTSZ levels and treatment responses. Results: CTSZ was upregulated in ccRCC tissues compared with adjacent normal tissues at the RNA but not in ccRCC cells. Immunohistochemistry indicated that CTSZ was expressed in tumors infiltrated with lymphocytes. Double immunofluorescence demonstrated that CTSZ was co-expressed with CD68 but not CD8. Single-cell transcriptome data showed macrophage-specific expression of CTSZ in ccRCC. High CTSZ expression was significantly correlated with the enrichment of interferon-γ, epithelial-to-mesenchymal transition, cell cycle, apoptosis pathways, and B cell, macrophage, neutrophil, and dendritic cell infiltrations, as well as the expression of immune checkpoints CTLA4, LAG3, HAVCR2, PDCD1LG2, PDCD1, TIGIT, and SIGLEC15. Hypomethylation modification of cg02744249, cg02744249, and cg22145559 were negatively correlated with CTSZ expression, suggesting an epigenetic mechanism for the regulation of CTSZ expression. Clinically, CTSZ levels were associated with the prognosis of patients with ccRCC (hazard ratio=1.5, P=0.007). Notably, patients with higher CTSZ expression had a worse prognosis with anti-PD-1 monotherapy (hazard ratio=1.51, P=0.039). Conclusion: Macrophage-specific CTSZ was associated with activation of epithelial-to-mesenchymal transition, cell cycle signatures, and a higher infiltration level of B cells, macrophages, neutrophils, and dendritic cells in the tumor microenvironment. High expression of CTSZ could be considered as a prognostic and treatment response biomarker for patients with ccRCC receiving anti-PD-1 immunotherapy.

Integrated Analysis of Energy Metabolism Signature-Identified Distinct Subtypes of Bladder Urothelial Carcinoma.

Background: Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Methods: The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database. A consensus clustering algorithm was then conducted to classify the patients into two clusters. Tumor prognosis, clinicopathological features, mutations, functional analysis, ferroptosis status analysis, immune infiltration, immune checkpoint-related gene expression level, chemotherapy resistance, and tumor stem cells were analyzed between clusters. An energy metabolism-related signature was further developed and verified using data from cBioPortal datasets. Results: Two clusters (C1 and C2) were identified using a consensus clustering algorithm based on an energy metabolism-related signature. The patients with subtype C1 had more metabolism-related pathways, different ferroptosis status, higher cancer stem cell scores, higher chemotherapy resistance, and better prognosis. Subtype C2 was characterized by an increased number of advanced BLCA cases and immune-related pathways. Higher immune and stromal scores were also observed for the C2 subtype. A signature containing 16 energy metabolism-related genes was then identified, which can accurately predict the prognosis of patients with BLCA. Conclusion: We found that the energy metabolism-associated subtypes of BLCA are closely related to the immune microenvironment, immune checkpoint-related gene expression, ferroptosis status, CSCs, chemotherapy resistance, prognosis, and progression of BLCA patients. The established energy metabolism-related gene signature was able to predict survival in patients with BLCA.

Generating comprehensive comparative evidence on various interventions for penile rehabilitation in patients with erectile dysfunction after radical prostatectomy: a systematic review and network meta-analysis.

BACKGROUND: We aim to present a comprehensive comparison of various treatments in the management of penile recovery after radical prostatectomy (RP) and provide recommendations for future research. METHODS: Literature search of electronic databases including PubMed, the Cochrane Library, Embase, PsycInfo, and Web of Science, and manual retrieval were conducted from inception through March 2020. "Erectile dysfunction" and "prostatectomy" were used as the Mesh terms. The patients, intervention, comparison, outcome, and study design (PICOS) approach were used to define study eligibility. Two authors independently selected studies, evaluated the methodological quality, and extracted data using Cochrane Collaboration's tools. The data analysis was completed by STATA version 14.2. RESULTS: A total of 24 studies with 3,500 patients were incorporated in the final analysis after screening 6,131 records. Our findings indicated that vacuum constriction devices (VCD) ranked 1st which meant that patients in VCD group had the best effect regarding mean IIEF scores within 3 months after RP, and no significant difference was observed between VCD and VCD with 20 mg/day tadalafil (V20DT) (MD: 5.44; 95% CI: -0.81 to 11.69). VCD and 50 mg/day sildenafil (VC50DS) showed superiority over 50 mg/day sildenafil (50DS) (MD: 3.75; 95% CI: 2.74-4.76) and intraurethral alprostadil 125-250 µg (MD: 3.05; 95% CI: 0.38 to 5.72), respectively. Moreover, V20DT showed significant superiority over the other interventions for ≥6 months mean International Index Erectile of Function (IIEF) scores after RP. Monotherapy appeared to have similar efficacy in terms of mean IIEF scores and proportion of patients return to baseline, and the effect of phosphodiesterase type 5 inhibitors (PDE5is) did not seem to be affected by the patterns of administration (regular or on demand). CONCLUSIONS: The combination therapy showed certain advantages over monotherapy, and we recommended the combination of VCD and PDE5is to be considered in the clinical management of penile rehabilitation after RP.