Evaluation of efficacy and safety of low-intensity pulsed ultrasound in patients with concurrent erectile dysfunction and chronic prostatitis/chronic pelvic pain syndrome: a prospective, randomized controlled study.

OBJECTIVE: The primary objective of this clinical trial is to investigate the effect of low-intensity pulsed ultrasound (LIPUS) on patients suffering from comorbid erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS). METHODS: The clinical trial was conducted in the andrology outpatient treatment room of the Department of Urology, Xiangya Hospital, Central South University from August to November 2022 A total of 60 patients who met the research criteria for comorbid ED combined with CP/CPPS were recruited and randomly assigned to three treatment groups. They were treated with LIPUS (Group A), drug therapy(Group B), and LIPUS combined with drug therapy (Group C), respectively. Each group comprised 20 patients. Statistical analysis was performed on the five-item version of International Index of Erectile Function (IIEF-5), Erection Hardness Score (EHS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the nine-item Patient Health Questionnaire (PHQ-9), the seven-item Generalized Anxiety Disorder Scale (GAD-7), and the incidence of adverse events to comprehensively evaluate the efficacy and safety of LIPUS. RESULTS: The positive response rate of ED and CP/CPPS treatment in Group A is 40%(8/20) and 45%(9/20), while those in Group B is 55%(11/20) and 60%(12/20), and those in Group C is 85%(17/20) and 85%(17/20). A notable increase in IIEF-5 scores was observed across the three groups post-treatment (10.45 ± 2.50 vs. 13.65 ± 3.03, P = 0.008; 11.80 ± 3.21 vs. 16.40 ± 3.20, P = 0.011; 12.90 ± 3.92 vs. 19.40 ± 2.35, P = 0.042) with a concomitant significant decrease in NIH-CPSI scores (16.75 ± 4.53 vs. 14.65 ± 4.51, P = 0.016; 16.35 ± 4.32 vs. 12.20 ± 4.74, P = 0.007; 16.00 ± 4.40 vs. 8.15 ± 4.28, P = 0.021). Notably, the most pronounced changes were seen in the group receiving LIPUS combined with tadalafil and doxazosin. Additionally, all groups exhibited marked improvements in anxiety and depression symptoms post-treatment. No adverse events were observed during treatment. CONCLUSION: LIPUS can improve erectile function and CP/CPPS symptoms with good safety, and LIPUS combined with tadalafil and doxazosin is more effective during the treatment. However, its long-term efficacy remains to be seen. TRIAL REGISTRATION: Chinese Clinical Trial Registry; approval number: ChiCTR2200063038 ( https://www.chictr.org.cn/ ) on August 29, 2022.

Verapamil inhibits inflammation and promotes autophagy to alleviate ureteral scar by regulation of CaMK IIδ/STAT3 axis.

BACKGROUND: Ureteral stricture (US) is a pathological stenosis in the urinary tract characterized by increased collagen synthesis and inflammation. Autophagy activation has been shown to ameliorate tissue fibrosis and protect against fibrotic diseases. Verapamil has beneficial therapeutic benefits on fibrotic disorders. The pharmacological effects of verapamil on fibroblast autophagy in US and the underlying mechanism need to be investigated further. METHODS: US patients were recruited to isolate scar tissues, hematoxylin-eosin (HE) and Masson trichrome staining were performed to analyze histopathological changes. The US animal model was established and administered with verapamil (0.05 mg/kg) in the drinking water. Transforming growth factor (TGF)-ß1 was adopted to facilitate collagen synthesis in fibroblasts. The mRNA and protein expressions were examined by qRT-PCR, western blot, immunofluorescence and immunohistochemistry. ELISA was adopted to measure interleukin (IL)-1ß and IL-6 levels. Molecular interaction experiments like dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between signal transducers and activators of transcription 3 (STAT3) and RNA polymerase II associated factor 1 (PAF1). RESULTS: Herein, our results revealed that verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited inflammation and fibrosis by repressing Ca2+/calmodulin-dependent protein kinase II (CaMK II) δ-mediated STAT3 activation. Our following tests revealed that STAT3 activated PAF1 transcription. PAF1 upregulation abrogated the regulatory effect of verapamil on fibroblast autophagy and fibrosis during US progression. Finally, verapamil mitigated US in vivo by activating fibroblast autophagy. CONCLUSION: Taken together, verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited fibrosis by repressing the CaMK IIδ/STAT3/PAF1 axis.

A novel trauma induced urethral stricture in rat model.

Urethral stricture (US) is a longstanding disease, while there has not existed a suitable animal model to mimic the condition. We aimed to establish a trauma-induced US animal model to simulate this clinical scenario. A total of 30 rats were equally distributed into two groups, sham and US group. All rats were anesthetized with isoflurane and undergone cystostomy. In the US group, a 2 mm incision was made in the urethra and sutured to induce US. The sham group only make a skin incision on the ventral side of the anterior urethra. 4 weeks later, ultrasound and cystourethrography were performed to evaluate the degree of urethral stricture, pathological examinations were carried out to evaluate the degree of fibrosis. Urodynamic evaluation and mechanical tissue testing were performed to evaluate the bladder function and urethral tissue stiffness. The results showed that the urethral mucosa was disrupted and urethral lumen was stenosed in the US group. Additionally, the US group showed elevated bladder pressure, prolonged micturition intervals and increased tissue stiffness. In conclusion, the rat urethral stricture model induced by trauma provides a closer representation of the real clinical scenario. This model will significantly contribute to advancing research on the mechanisms underlying traumatic urethral stricture.

Effects of internet-based exercise intervention on depression and anxiety: A systematic review and meta-analysis.

BACKGROUND: While exercise is acknowledged for its positive effects on depression and anxiety symptoms, the benefits of internet-based exercise on mental health have not been extensively examined. This study seeks to systematically review and quantify the outcomes of high-quality randomized controlled trials (RCTs) that investigate the impact of internet-based exercise on depression and anxiety symptoms. METHODS: Following the PRISMA 2020 guidelines, we conducted a comprehensive meta-analysis of RCTs. Databases, including Web of Science Core Collection, PubMed, PsycINFO, Medline, BIOSIS Previews, SPORTDiscus, and Education Source, were scoured through in September 2023. After quality assessment and data extraction, the analysis was performed using R. Using random effects models, effect sizes were determined and subsequently represented as standardized mean differences (SMD). RESULTS: Our analysis incorporated data from 11 RCTs, involving a cohort of 1009 participants. We observed a modest yet significant reduction in depression and anxiety symptoms, with an SMD of -0.44 [95% confidence interval (CI) (-0.63, -0.26), I^2 = 79.3%, P < .01]. Interestingly, the effects were more pronounced in individuals diagnosed with depression, as indicated by an SMD of -0.96 [95% CI (-1.55, -0.37), I^2 = 82%, P < .01]. Furthermore, participants utilizing smartphone applications as part of their intervention reported a meaningful reduction in their symptoms, evidenced by an SMD of -0.52 [95% CI (-0.90, -0.14), I^2 = 87%, P < .01]. Additionally, short-term interventions, specifically those lasting <12 weeks, indicated a notable alleviation in depression symptoms, with an SMD of -0.76 [95% CI (-1.38, -0.14), I^2 = 86%, P < .01]. CONCLUSION: Internet-based exercise interventions yield significant amelioration in depression and anxiety symptoms, with heightened efficacy observed among individuals with depression. Notably, short-term interventions, specifically those under 12 weeks, demonstrate enhanced benefits for depression relief.

Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, and it demonstrates high clinical heterogeneity and complex genetic architecture. A variation within TRMT2B (c.1356G>T; p.K452N) was identified to be associated with ALS in a family comprising two patients with juvenile ALS (JALS). Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS, and three more variants were identified in a public ALS database including 3317 patients with ALS. A decreased number of mitochondria, swollen mitochondria, lower expression of ND1, decreased mitochondrial complex I activities, lower mitochondrial aerobic respiration, and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 cells. Further, TRMT2B variations overexpression cells also displayed decreased ND1. In conclusion, a novel JALS-associated gene called TRMT2B was identified, thus broadening the clinical and genetic spectrum of ALS.

Extracellular matrix stiffness aggravates urethral stricture through Igfbp3/Smad pathway.

Urethral stricture refers to the narrowing of the urethral lumen. While previous studies have hinted at inflammation as the initial driver of this condition, the reasons and mechanisms behind its progression remain largely unknown. By Atomic force microscope (AFM), researchers measured the matrix stiffness of urethra to be 5.23 ± 0.37 kPa for normal tissue and 41.59 ± 2.48 kPa for stricture urethral scar. Similar results were observed in rat urethral stricture models, where the matrix stiffness of normal urethra was 4.29 ± 0.82 kPa, while 32.94 ± 7.12 kPa for urethral stricture scar. Notably, the matrix stiffness increased in rat models over time. To further investigate, polyacrylamide hydrogels were employed to mimic different levels of stiffness for normal and stricture condition. Interestingly, higher matrix stiffness led to an increased fibroblast-to-myofibroblast transition (FMT) in rat urethral fibroblasts, indicated by enhanced expression of α-SMA and Collagen I, as well as changing in the morphology of fibroblast. RNA-seq analysis suggested that Igfbp3/Smads might regulate the progressive FMT in urethral stricture. In the experiment where the expression of Igfbp3 was inhibited, increasing matrix stiffness lose the potential to stimulate FMT progression and the expression of p-Smad2/3 decreased. On the contrary, overexpression of Igfbp3 promoted the process of FMT in urethral fibroblasts. In conclusion, Igfbp3/Smad pathway appeared to be involved in the progression of urethral fibrosis. This finding suggested that Igfbp3/Smad might be an promising target for future research and treatment in this filed.

Anesthesia Analysis of Compound Lidocaine Cream Alone in Adult Male Device-Assisted Circumcision.

OBJECTIVE: to evaluate the anesthetic effect among adult male patients with the single use of compound lidocaine cream in device-assisted circumcision, hoping to provide an anesthetic method for the simplification of the surgical process. METHODS: Male adult patients undergoing device-assisted circumcision through prepuce local anesthesia using lidocaine cream in Xiangya Hospital of Central South University from December 2020 to August 2021 were selected. According to different age groups and different surgical procedures, the anesthetic effect of compound lidocaine cream was analyzed considering the aspects of anesthetic cost, anesthetic time, anesthetic duration, anesthetic effect, anesthetic side effects and anesthetic satisfaction. RESULTS: In the study, 99.1% of 649 patients needed only 1 application of compound lidocaine cream to complete the operation. The time taken for anesthesia was short; the whole anesthesia process only required approximately 2-5 min. However, for patients with severe phimosis, the time to complete the anesthesia procedure was correspondingly longer. The pain degree caused by anesthesia was low, and the patients with a pain score of ≤3 points accounted for 96.7%. The anesthetic effect lasted for a sufficiently long period, and the time of algesia recovery from local anesthesia was almost 1 h after surgery. The anesthesia effect was sufficient, and patients with an intraoperative pain score of ≤3 accounted for 98.7%, which could meet the surgical requirements. There were few side effects of the anesthesia. The overwhelming majority of patients were pleased with the anesthesia, and 98.9% of patients had an anesthesia satisfaction score of ≥7. CONCLUSION: The compound lidocaine cream, as a local anesthetic, is safe and effective for most adult male device-assisted circumcisions. More useful information needs to be corroborated by more advanced evidence, especially for severe phimosis.

Venous Thromboembolism and Bleeding after Transurethral Resection of the Prostate (TURP) in Patients with Preoperative Antithrombotic Therapy: A Single-Center Study from a Tertiary Hospital in China.

BACKGROUND: Venous thromboembolism (VTE) and postoperative hemorrhage are unavoidable complications of transurethral resection of the prostate (TURP). At present, more and more patients with benign prostate hyperplasia (BPH) need long-term antithrombotic therapy before operation due to cardiovascular diseases or cerebrovascular diseases. The purpose of this study was to investigate the effect of preoperative antithrombotic therapy history on lower extremity VTE and bleeding after TURP. METHODS: Patients who underwent TURP in the Department of Urology, Xiangya Hospital, Central South University, from January 2017 to December 2021 and took antithrombotic drugs before operation were retrospectively analyzed. The baseline data of patients were collected, including age, prostate volume, preoperative International Prostate Symptom Score (IPSS), complications, surgical history within one month, indications of preoperative antithrombotic drugs, drug types, medication duration, etc. Main outcome measures included venous thromboembolism after TURP, intraoperative and postoperative bleeding, and perioperative blood transfusion. Secondary outcome measures included operation duration and postoperative hospitalization days, the duration of stopping antithrombotic drugs before operation, the recovery time of antithrombotic drugs after operation, the condition of lower limbs within 3 months after operation, major adverse cardiac events (MACEs), and cerebrovascular complications and death. RESULTS: A total of 31 patients after TURP with a long preoperative history of antithrombotic drugs were included in this study. Six patients (19.4%) developed superficial venous thrombosis (SVT) postoperatively. Four of these patients progressed to deep vein thrombosis (DVT) without pulmonary thromboembolism (PE). Only one patient underwent extra bladder irrigation due to blockage of their urinary catheter by a blood clot postoperatively. The symptoms of hematuria mostly disappeared within one month postoperatively and lasted for up to three months postoperatively. No blood transfusion, surgical intervention to stop bleeding, lower limb discomfort such as swelling, MACEs, cerebrovascular complications, or death occurred in all patients within three months after surgery. CONCLUSION: Short-term preoperative discontinuation may help patients with antithrombotic therapy to obtain a relatively safe opportunity for TURP surgery after professional evaluation of perioperative conditions. The risks of perioperative bleeding, VTE, and serious cardiovascular and cerebrovascular complications are relatively controllable. It is essential for urologists to pay more attention to the perioperative management of these patients. However, further high-quality research results are needed for more powerful verification.

Incidence and risk factors of in-hospital venous thromboembolism in non-oncological urological inpatients: A single center experience.

Objective: To determine incidence and risk factors for venous thromboembolism (VTE) development of in-hospital VTE in urological inpatients who underwent non-oncological surgery in a tertiary hospital in China. Methods: Consecutive 1453 inpatients who were admitted to a non-oncological urological ward in the tertiary hospital from January 1, 2018 to December 31, 2018 were enrolled in the study, and the VTE events were diagnosed by ultrasound or computed tomographic pulmonary angiography. Patients' occurrence of VTE and characteristics which may contribute to the development of VTE were collected and analyzed as incidence and risk factors. Results: The incidence of VTE in non-oncological urological inpatients is 2.3%. In our cohort, patients who experienced previous VTE (adjusted odds ratios [aOR] 14.272, 95% CI 3.620-56.275), taking anticoagulants or antiplatelet agents before admission (aOR 10.181, 95% CI 2.453-42.256), D-dimer (max) ≥1 µg/mL (aOR 22.456, 95% CI 6.468-77.967), lower extremity swelling (aOR 10.264, 95% CI 2.242-46.994), chest symptoms (aOR 79.182, 95% CI 7.132-879.076), operation time of more than or equal to 180 min (aOR 10.690, 95% CI 1.356-84.300), and Caprini score (max) of more than or equal to 5 (aOR 34.241, 95% CI 1.831-640.235) were considered as risk factors for VTE. Conclusion: In this study, we found that the incidence of VTE in non-oncological surgery was about 2.3%, which was higher than some previous studies. Risk factors could be used for early detection and diagnosis of VTE.

The effect of different types of physical activity on cognitive reaction time in older adults in China.

Introduction: Aging is not only reflected in the degeneration of physiological functions but is also embodied in the decline of psychological and cognitive functions. The decline of cognitive function can reduce the quality of life in older adults, and even potentially cause Alzheimer's disease, which may lead to a heavy burden on patients, families, and society. The purpose of this study was to investigate the effects of physical activity (PA) on cognitive reaction time in older adults. Methods: A cross-sectional survey design was used in this study. A total of 839 elderly subjects were recruited from Beijing and Shanghai. In total, 792 subjects met the inclusion criteria (age > 60 years, without disability, speech, and hearing impairment), including 384 men (age:67.7 ± 5.7 years) and 408 women (age: 68.2 ± 5.8 years). The PA was assessed by the Physical Activity Scale for the Elderly (PASE). All kinds of PA were divided into three levels: "Low" (< 50% average score), "Moderate" (50-150% average score), and "High" (>150% average score). The reaction time of subjects was measured by the selective reaction tester (Model: CSTF-XF, TFHT, Beijing, China). Results: For leisure-time PA, the results showed that the cognitive reaction time of older adults in the "Low" group (1.11 ± 0.32 s) was significantly longer than that in the "Moderate" group (1.05 ± 0.30 s, p < 0.01) and the "High" group (0.99 ± 0.28 s, p < 0.01). For housework PA, there was no significant difference in the cognitive reaction time among the three groups ("Low": 1.09 ± 0.31 s; "Moderate": 1.07 ± 0.31 s; "High": 1.05 ± 0.28 s, p > 0.05). For work-related PA, the results showed that the cognitive reaction time of older adults in the "Low" group (1.09 ± 0.30 s) was significantly longer than that in the "High" group (0.99 ± 0.28 s) and the "Moderate" group (1.03 ± 0.32 s, p < 0.01). Conclusion: The PA has a positive effect on reducing cognitive reaction time in older adults. It is recommended that older adults maintain a moderate level of leisure PA and work-related PA to delay the decline in cognitive reaction time.

Effects of aquatic exercise on mood and anxiety symptoms: A systematic review and meta-analysis.

Objective: Exercise has beneficial effects on mood and anxiety symptoms. However, the impact of aquatic exercise on mood and anxiety symptoms has not been clearly confirmed. Therefore, this study aimed to synthesize and systematically analyze evidence available on boosting mental health through aquatic exercise. Method: A systematic review and meta-analysis were conducted under the PRISMA 2020 guidelines. PubMed, BIOSIS Previews, PsycINFO, Medline, SPORTDiscus, Education Source, and Web of Science Core Collection (WoSCC) were searched in May 2022. The research included the influence of aquatic exercises on mood and anxiety symptoms. After assessing trial quality and completing data extraction, a meta-analysis was carried out through R software. The results were presented as a standardized mean difference (SMD) and the corresponding 95% confidence interval. Results: A total of 18 original trials were included. People who received aquatic exercise intervention had a statistically significant reduction in mental disorder symptoms compared with before. The results were aquatic exercise [SMD = -0.77, 95% CI (-1.08, -0.47), I2 = 77%, P < 0.01], swimming [SMD = -0.51, 95% CI (-1.14, 0.12), I2 = 78%, P < 0.01], aquatic aerobics [SMD = -0.92, 95% CI (-1.32, -0.53), I2 = 78%, P < 0.01], moderate intensity [SMD = -0.75, 95% CI (-1.07, -0.43), I2 = 67%, P < 0.01], and low intensity [SMD = -1.07, 95% CI (-1.08, -0.47), I2 = 85%, P < 0.01]. Conclusion: Aquatic exercise could statistically significantly improve mental health. Light aquatic aerobics probably has a better effect on mood and anxiety symptoms. However, given the number and quality of included research, verifying the aforementioned conclusions requires a larger sample of high-quality studies.

Pulmonary embolism following urological non-oncological surgery: The clinical features, management, and long-term follow-up outcome from a tertiary hospital of China.

Objective: To evaluate the clinical features, treatment, and outcomes of pulmonary embolism (PE) after urological non-oncological surgery in a tertiary hospital of China. Methods: A total of eight patients who suffered from PE after urological non-oncological surgery from 2016 to 2019 were recruited to the study. Clinical data such as symptoms, vital signs, electrocardiogram, echocardiography, and computed tomographic pulmonary arteriography (CTPA) were reviewed. In addition, the management and long-term follow-up outcome of PE were reported. Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire was applied for five patients to evaluate health-related quality of life after PE. Results: All patients survived during their hospitalization, and five patients were contacted during follow-up. Five of the eight patients were anticoagulated regularly until the re-examination results of CTPA and lower extremities ultrasound were normal. The period of anticoagulant sustained at least one month for each patient. The long-term follow-up outcomes showed that PE had little impact on the patients' quality of life. Conclusions: The study demonstrated that the prognosis of PE patients was not as terrible as feared when treated immediately in the ward. Early diagnosis and treatment of PE is vital for prognosis. However, further verifications based on the results of large studies are still needed.

Transperitoneal Laparoscopic Unroofing versus Fenestration Under Seminal Vesiculoscopy for Seminal Vesicle Cyst, a Multi-Institutional Retrospective Cohort Study.

Background: To illustrate the transperitoneal laparoscopic unroofing (TLU) and compare the efficacy and safety of TLU to fenestration under seminal vesiculoscopy (FUSV) in treating symptomatic seminal vesicle cyst (SVC). Methods: We retrospectively reviewed all patients with symptomatic SVC who underwent TLU or FUSV between 2008 and 2020 at 3 institutions in Hunan. The two groups were evaluated with reference to radiological failure-free survival (R-FFS), fertility outcome, symptoms, and complications at a median 33.5-month follow-up. Results: Of the 98 males, 58 (59.2%) received TLU, and 40 (40.8%) underwent FUSV. Baseline characteristics were comparable. Semen analysis, prostatitis-like symptoms, and the maximum diameter of cyst were partially improved after both surgeries at 12-month follow-up. The TLU groups suggested a higher incidence rate of fertility for SVC patients with comorbid infertility compared with the FUSV group (82.4% vs 70.3%, p = 0.041), as well as better R-FFS of cysts at five-year follow-up (Log rank test, p = 0.021). In addition, the number of patients with NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index) scores higher than 15 decreased more significantly after TLU (p = 0.004). Except for hematospermia within 3 months, no significant difference in adverse events was observed in the two groups during the long-term follow-up. Conclusion: TLU was superior for patients with large and symptomatic SVC to FUSV, with more relieved symptoms, better R-FFS of cysts and fertility outcomes. Registration Number of Clinical Trial: ChiCTR2100053850 in Chinese Clinical Trial Registry Platform (ChiCTR).

Establishment of Prediction Models for Venous Thromboembolism in Non-Oncological Urological Inpatients - A Single-Center Experience.

Purpose: Venous thromboembolism (VTE) comprises deep venous thrombosis (DVT) and pulmonary embolism (PE), which can lead to death. VTE is an insidious disease with no specific symptoms and overlooked readily. We aimed to establish prediction models for VTE in non-oncological urological inpatients to aid urologists to better identify VTE patients. Patients and Methods: A retrospective analysis of 1453 inpatients was carried out. The risk factors for VTE had been clarified in our previous study. A stepwise regression method was used to screen the relevant influencing factors for VTE and construct a logistic regression prediction model to predict VTE. To validate the accuracy of the model, data from 291 patients from another cohort were used for external validation. Results: A total of 1453 inpatients were enrolled. Five potential risk factors (previous VTE; treatment with anticoagulants or anti-platelet agents before hospital admission; D-dimer ≥0.89 µg/mL; lower-extremity swelling; chest symptoms) were selected by multivariable analysis with p < 0.05. These five risk factors were used to build a logistic regression prediction model. When p < 0.1 in the multivariable logistic regression model, two additional risk factors were added: Caprini score ≥5 and complications, and all seven risk factors were used to build another prediction model. Internal verification showed the cutoff values, sensitivity, and specificity of the two models to be 0.02474, 0.941, 0.816 (model 1) and 0.03824, 0.941, and 0.820 (model 2), respectively. Both models had good predictive ability, but prediction accuracy was 43.0% for both when using the data of the additional 291 inpatients in the two models. Conclusion: Two novel prediction models were built to predict VTE in non-oncological urological inpatients. This is a new method for VTE screening, and internal validation showed a good performance. External validation results were suboptimal but may provide clues for subsequent VTE screening.

Comprehensive Characterization of Ageing-Relevant Subtypes Associated With Different Tumorigenesis and Tumor Microenvironment in Prostate Cancer.

Objective: Accumulated evidence demonstrates that ageing is a robust risk factor of prostate cancer prognosis. Herein, we conducted a systematic analysis about ageing-relevant molecules and relevant tumor microenvironment features in prostate cancer. Methods: Transcriptome data, clinical information, and mutational data of prostate cancer patients were retrospectively collected from the Cancer Genome Atlas cohort. In accordance with the expression of specific ageing-relevant genes, prostate cancer patients were clustered with consensus clustering analyses. WGCNA was adopted for determination of subtype-associated co-expression modules and genes. Thereafter, characteristic genes were further screened with random forest algorithm and a prognostic model was conducted with multivariate cox regression analyses. Tumor microenvironment-infiltrating immune cells were estimated with ssGSEA and ESTIMATE. Activities of the cancer immunity cycle and expressions of HLA and immune checkpoint molecules were then quantified across prostate cancer cases. A serious experiment was conducted to investigate the roles of EIF2S2 in prostate tumorigenesis. Results: This study characterized three ageing-relevant subtypes (C1, C2, and C3) with diverse clinical prognosis. Subtype C1 presented the features of low mutational frequency and immune activation; C2 was characterized by stromal and immune activation; and C3 showed immune suppression. An ageing-derived gene signature was conducted, which independently and robustly predicted patients' prognosis. Additionally, this signature was in relation to immune inactivation. Among the genes in the signature, EIF2S2 triggered proliferation, invasion, and migration of LNCaP and PC-3 cells. Conclusion: Collectively, ageing-relevant molecular subtypes and gene signature might be of great significance to determine clinical outcomes and tumor microenvironment features and immunotherapeutic responses in prostate cancer.

Transcriptomic analysis of bladder tissue in a rat model of ketamine-induced bladder fibrosis.

INTRODUCTION: Ketamine-induced cystitis (KIC) is a disease caused by ketamine that can cause lower urinary tract symptoms (LUTS). Its end-stage is bladder contracture, which is related to bladder fibrosis and poses a serious burden to patient lives. METHODS: We established a KIC model in female Sprague Dawley rats and verified bladder fibrosis in the model by Masson trichrome staining and western blot analysis. The bladders of the rats from the ketamine and control groups were used to perform transcriptome analysis. In particular, association analysis with metabolomics was also used to determine the potential mechanisms of ketamine-induced bladder fibrosis. RESULTS: A total of 685 differentially expressed messenger RNAs, 71 differentially expressed long noncoding RNAs, 23 differentially expressed microRNAs, and 68 differentially expressed circular RNAs were identified. We found that ribosome, Wnt signaling, vascular endothelial growth factor signaling, cytoskeleton organization, and cytoskeletal protein binding may be potential pathways in ketamine-induced bladder fibrosis as identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. In addition, the mitogen-activated protein kinase pathway appeared to be closely related to the development of ketamine-induced bladder fibrosis according to association analysis. CONCLUSIONS: In this study, using transcriptomic and correlation analyses of metabolomics, we identified pathways that may be potential targets for the prevention and treatment of ketamine-induced bladder fibrosis.

Dkk3/REIC Deficiency Impairs Spermiation, Sperm Fibrous Sheath Integrity and the Sperm Motility of Mice.

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×106), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice.

Incidence, Risk Factors, Risk Assessment Model and Compliance of Patients on Anticoagulants for Asymptomatic Venous Thromboembolism in Nononcological Urological Inpatients.

PURPOSE: To study the incidence, risk factors for developing asymptomatic venous thromboembolism and the compliance of patients on anticoagulants for asymptomatic venous thromboembolism (VTE) in nononcological urological medium-high risk inpatients, and build a risk assessment model (RAM) for early screening for asymptomatic VTE. MATERIALS AND METHODS: We conducted a retrospective analysis of 573 inpatients admitted to a nononcological urological ward of a tertiary hospital in China from January 1, 2017, to June 30, 2019. Data were collected using the electronic medical record system, and patients underwent a follow-up by phone 6 months after discharge. RESULTS: Among the 573 medium-high risk inpatients, 73 (15.4%) were diagnosed with VTE, including 20 (4.2%) symptomatic and 53 (11.2%) asymptomatic. Prior history of VTE, a history of anticoagulants or antiplatelet agents before admission, and D-dimer ≥ 1 were the potential risk factors identified for asymptomatic VTE. Patients with poor awareness of VTE and its dangers, and patients who lived more than 1 hour away from the hospital had a high probability of poor compliance with anticoagulation therapy after discharge. Using D-dimer (1.785 µg/ml), we built a RAM for the early diagnosis of asymptomatic VTE. CONCLUSION: We found that patients with urinary nontumor VTE had low compliance with anticoagulation therapy after discharge. The key factors for determining asymptomatic VTE in nononcological urological inpatients included prior history of VTE, a history of taking anticoagulants or anti-platelet agents before admission, and D-dimer ≥ 1. Furthermore, we found that the threshold of D-dimer should be elevated to 1.785 µg/ml to predict asymptomatic VTE.