The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Robot-Assisted Radical Prostatectomy by the Hugo Robotic-Assisted Surgery (RAS) System and the da Vinci System: A Comparison between the Two Platforms.

OBJECTIVE: In a previous study, we proved that an experienced urologist is more likely to adapt to the Hugo RAS system. Based on this, we further examine various parameters in this study. Parameters included in this study consisted of console time, functional outcomes, and oncological outcomes. MATERIALS AND METHODS: A total of 60 patients who underwent robot-assisted radical prostatectomy (RARP) performed by a single surgeon using the da Vinci (DV) system (n = 30) or the Hugo RAS system (n = 30) between March 2023 and August 2023 were included in the analysis. The intraoperative operative time was categorized into vesicourethral anastomosis time and overall console time. Functional and oncological outcomes were documented at the 1st and 3rd postoperative months. Parametric and non-parametric methods were adopted after checking skewness and kurtosis, and an α value of 5% was used to determine the significance. RESULTS: The vesicourethral anastomosis time was significantly lengthened (Hedge's g: 0.87; 95% confidence interval (CI): 0.34-1.39; J factor = 0.987). However, the overall console time was not affected. The functional (postoperative 3rd month: p = 0.130) and oncological outcomes (postoperative 3rd month: p = 0.103) were not significantly different. We also found that the adverse effect on surgical specimens and positive surgical margins was not affected (p = 0.552). CONCLUSION: During the process of adaptation, although intricate motions (such as the vesicourethral anastomosis time) would be lengthened, the overall console time would not change remarkably. In this process, the functional and oncological outcomes would not be compromised. This encourages urologists to adopt the Hugo RAS system in RARP if they have previous experiences of using the DV system, since their trifecta advantage would not be compromised.

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma.

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

Primary sclerosing epithelioid fibrosarcoma of the kidney: A rare case report.

Sclerosing epithelioid fibrosarcoma (SEF) represents a rare variant of fibrosarcoma primarily arising in the deep soft tissue of the extremities and trunk. The author reported a rare case of SEF emerged primarily in the kidney. Clinically, the patient complained of hematuria. The diagnosis was confirmed by histological examination and immunohistochemical staining of MUC4. Subsequent fluorescence in situ hybridization (FISH) analysis detected the presence of EWSR1 gene rearrangement, further confirming the histological diagnosis. The patient has been alive with 12 months follow-ups after nephrectomy. The disease should be considered in the differential diagnosis for primary renal tumors.

Skin sympathetic nerve activity as a potential biomarker for overactive bladder.

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.

Cumulative sum analysis of the learning curve of laparoendoscopic single-site robot-assisted radical prostatectomy.

BACKGROUND: Radical prostatectomy has become the gold standard for treating localized prostate cancer. Improvement in the single-site technique and surgeon's skill reduces not only the hospital duration but also the number of wounds. Realizing the learning curve for a new procedure can prevent unnecessary mistakes. OBJECTIVE: To analyze the learning curve of extraperitoneal laparoendoscopic single-site robot-assisted radical prostatectomy (LESS-RaRP). METHODS: We retrospectively evaluated 160 patients diagnosed with prostate cancer during June 2016 to December 2020 who underwent extraperitoneal LESS-RaRP. Calculated cumulative sum analysis (CUSUM) was used to evaluate the learning curves for the extraperitoneal setting time, robotic console time, total operation time, and blood loss. The operative and functional outcomes were also assessed. RESULTS: The learning curve of the total operation time was observed in 79 cases. For the extraperitoneal setting and robotic console times, the learning curve was observed in 87 and 76 cases, respectively. The learning curve for blood loss was observed in 36 cases. No in-hospital mortality or respiratory failure was observed. CONCLUSION: Extraperitoneal LESS-RaRP using the da Vinci Si system is safe and feasible. Approximately 80 patients are required to achieve a stable and consistent operative time. A learning curve for blood loss was observed after 36 cases.

High MRE11 Expression Level Predicts Poor Survival in Upper Tract Urothelial Carcinomas.

Upper tract urothelial carcinoma (UTUC) is an aggressive malignancy with characteristics of high metastasis and poor prognosis. There are some particularly different features of UTUC between the Asian and Western countries. Double-strand break repair protein MRE11 is a component of the MRN complex that is involved in the DNA repair pathway. Emerging studies have focused on the role of MRE11 in human malignancies with conflicting results. We aimed to establish the relationship between MRE11 expression and the oncological outcome of UTUC. This study retrospectively reviewed 150 patients who underwent radical nephroureterectomy with pathologically confirmed UTUC. Pathologic slides were reviewed, and clinical parameters were collected. An immunohistochemical study was performed, and the cytoplasmic and nuclear-staining results of UTUC were recorded. The expression of MRE11 was analyzed to identify correlations with various clinicopathological parameters, metastasis-free survival, and cancer-specific survival (CSS). MRE11 expression was significantly correlated with patients with a high pathologic stage ( P =0.001), perineural invasion ( P =0.015), and tumor necrosis ( P =0.034). Upon univariate analysis, a high MRE11 expression was associated with poor metastasis-free survival ( P =0.014, 95% CI 1.18, 4.38) and poor CSS ( P =0.001, 95% CI 2.45, 27.75). Upon multivariable analysis, a high MRE11 expression was associated with poor CSS ( P =0.019, 95% CI 1.28, 15.65). In summary, MRE11 expression could serve as a potential predictor of prognosis in patients with UTUC.

Exploring the Association between Gut and Urine Microbiota and Prostatic Disease including Benign Prostatic Hyperplasia and Prostate Cancer Using 16S rRNA Sequencing.

Numerous microorganisms residing in the gastrointestinal and genitourinary tracts affect host health. We investigated stool and voided urine samples collected from patients with benign prostatic hyperplasia (BPH) or prostate cancer (PC) and a control group to explore the potential relationship between human microbiota and prostatic disease, and aimed to identify correlations and pathogenic taxonomic units. We studied microbial composition using 16S rRNA sequencing to identify operational taxonomic units (OTUs). Extracted genome was amplified and filtered sequences were used to classify OTUs based on their specific taxonomy. No statistically significant differences were observed in stool samples among the groups. However, urine samples indicated different microbiota compositions in different patient populations. The top five microbial genera that showed significant differences between the BPH and control groups were Alcaligenes, Pseudomonas, Lactobacillus, Akkermansia, and Cetobacterium. Faecalibacterium, Staphylococcus, Ruminococcaceae_UCG_002, Neisseria, and Agathobacter were the genera with the largest proportion differences when comparing the PC and control groups. We discovered that the urine microbiota composition of the BPH and PC groups was distinct from that of the control group. Due to the impact of microbiota on prostatic disease, it is necessary to identify specific microbes for further research.

Surgical outcome predictor analysis following hand-assisted or pure laparoscopic transperitoneal nephroureterectomy using the Taiwan upper urinary tract urothelial carcinoma database.

Purpose: Taiwan has a high incidence of upper tract urothelial carcinoma (UTUC). This study aimed to compare the surgical outcomes following transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) from the Taiwan nationwide UTUC collaboration database using different parameters, including surgical volumes. Materials and methods: The nationwide UTUC collaboration database includes 14 hospitals in Taiwan from the Taiwan Cancer Registry. We retrospectively reviewed the records of 622 patients who underwent laparoscopic nephroureterectomy between July 1988 and September 2020. In total, 322 patients who received TP-LNU or TP-HALNU were included in the final analysis. Clinical and pathological data and oncological outcomes were compared. Results: Of the 322 patients, 181 and 141 received TP-LNU and TP-HALNU, respectively. There were no differences in clinical and histopathological data between the two groups. No differences were observed in perioperative and postoperative complications. There were no significant differences in oncological outcomes between the two surgical approaches. In the multivariate analysis, the cohort showed that age ≥70 years, positive pathological lymph node metastasis, tumors located in the upper ureter, and male sex were predictive factors associated with an increased risk of adverse oncological outcomes. A surgical volume of ≥20 cases showed a trend toward favorable outcomes on cancer-specific survival [hazard ratio (HR) 0.154, p = 0.052] and marginal benefit for overall survival (HR 0.326, p = 0.019) in the multivariate analysis. Conclusion: Although different approaches to transperitoneal laparoscopic nephroureterectomy showed no significant differences in surgical outcomes, age, sex, lymph node metastasis, and tumor in the upper ureter in the following period were predictive factors for oncological outcomes. Higher surgical volume did not impact disease-free survival and bladder recurrence-free survival but was associated with improved overall survival and cancer-specific survival. Exploration of unknown influencing factors is warranted.

Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth.

INTRODUCTION: Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated. METHOD: The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed. RESULT: The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.

High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.

BACKGROUND: Ubiquitin-mediated protein degradation has been reported to be involved in regulating the activity of oncoproteins and tumor suppressors. Dysfunction or dysregulation of the ubiquitin-proteasome system may induce tumorigenesis. Deubiquitinase ubiquitin-specific protease 2a (USP2a) has been reported to regulate cell growth or death and is involved in the pathogenesis of various diseases, including cancers. However, the role of USP2a in upper tract urothelial carcinoma (UTUC) has not been investigated yet. The goal of this study was to evaluate the clinical significance of USP2a expression in UTUC. MATERIALS AND METHODS: A total of 110 UTUC cases were included in this study. USP2a expression level was evaluated through immunohistochemistry staining, and the correlation of USP2a expression level with both clinical and pathologic variables was analyzed. RESULTS: High USP2a expression level was observed in 48 (43.6%) cancer specimens. USP2a expression level was significantly correlated with tumor stage (P=0.001), grade (P=0.033), and tumor recurrence (P=0.008). High USP2a expression level was correlated with poor disease-free survival (P=0.005) and cancer-specific survival (P<0.001). In addition, high USP2a expression level was an independent predictor of poor disease-free survival (hazard ratio=2.31; P=0.007) and cancer-specific survival (hazard ratio=5.49; P=0.009). CONCLUSIONS: This study indicated that USP2a protein expression level may be a potential biomarker for predicting UTUC patient survival. Further prospective studies are needed to investigate the role of USP2a in UTUC progression.

A clinical observational study of effectiveness of a solid coupling medium in extracorporeal shock wave lithotripsy.

This study aimed to investigate clinical effectiveness of stone disintegration by using isolation coupling pad ("icPad") as coupling medium to reduce trapped air pockets during extracorporeal shock wave lithotripsy (ESWL). Patients underwent ESWL between Oct. 2017 and May 2018 were enrolled in this clinical observational study. An electromagnetic lithotripter (Dornier MedTech Europe GmbH Co., Germany) was used in this study. Patients were divided into icPad group P1, P2 and semi-gel group C by different coupling medium. The energy level and total number of shock wave (SW) for group P1 and C was set at level 2 and 3000 and group P2 at level 3 and 2500. The successful stone disintegration rate (SSDR) was determined to evaluate the treatment outcome. All patients were evaluated by KUB film and ultrasonography after 90 days. Complications during ESWL were recorded. A total of 300 patients satisfied the inclusion criteria. There were no significant differences in characteristics of patients and stone among three groups. The corresponding SSDRs for patients in group P1, P2 and C was 73.0%, 73.2% and 55.3%, respectively. The SSDR in group P1 was statistically higher than Group C. Comparing to semi-liquid gel, coupling medium using by icPad could achieve better treatment outcome of stone disintegration in ESWL.

Prognostic value of renal function for upper tract urothelial carcinoma who underwent radical nephroureterectomy: Sex differences.

BACKGROUND/PURPOSE: Upper tract urothelial carcinoma (UTUC) is a relatively rare type of urothelial carcinoma. Additionally, only few reports have examined the sex differences in patients with UTUC. Therefore, the present study aimed to identify the sex factors affecting renal function in patients with UTUC who underwent radical nephroureterectomy (RNU). METHODS: Patients who underwent RNU for non-metastatic UTUC between 2000 and 2013 were retrospectively reviewed and divided into two groups by sex. The Kaplan-Meier method was applied to evaluate the effects of sex on survival, whereas for the other clinicopathological parameters, hazard ratios were evaluated using the Cox regression model. The analyses were also performed in patients with different chronic kidney disease (CKD) stages. RESULTS: A total of 368 patients were included, 147 men and 221 women. Female patients had a higher rate of anemia, advanced CKD stage, and dialysis. Male patients predominantly had a higher rate of smoking. The Kaplan-Meier analysis revealed no differences between sexes on recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariate analysis confirmed that ureteral tumors, advanced pathological tumor stage, and adjuvant chemotherapy indicated significantly worse survival outcomes in both sexes. However, only female patients with advanced CKD showed poorer RFS. After adjusting for renal function, the analysis found men had worse RFS. CONCLUSION: The female sex is significantly associated with a higher prevalence of advanced CKD stage, and dialysis among patients with UTUC who underwent RNU in our institute. Sex differences in renal function needs to be considered when evaluating survival.

Smart Blood Vessel Detection System for Laparoscopic Surgery.

OBJECTIVE: Compared with traditional surgery, laparoscopic surgery offers the advantages of smaller scars and rapid recovery and has gradually become popular. However, laparoscopic surgery has the limitation of low visibility and a lack of touch sense. As such, a physician may unexpectedly damage blood vessels, causing massive bleeding. In clinical settings, Doppler ultrasound is commonly used to detect vascular locations, but this approach is affected by the measuring angle and bone shadow and has poor ability to distinguish arteries from veins. To tackle these problems, a smart blood vessel detection system for laparoscopic surgery is proposed. METHODS: Based on the principle of near-infrared spectroscopy, the proposed instrument can access hemoglobin (HbT) parameters at several depths simultaneously and recognize human tissue type by using a neural network. RESULTS: Using the differences in HbT and StO2 between different tissues, vascular and avascular locations can be recognized. Moreover, a mechanically rotatable stick enables the physician to easily operate in body cavities. Phantom and animal experiments were performed to validate the system's performance. CONCLUSION: The proposed system has high ability to distinguish vascular from avascular locations at various depths.

Prognostic Value of Comorbidity for Patients with Upper Tract Urothelial Carcinoma after Radical Nephroureterectomy.

Patients with upper tract urothelial carcinoma (UTUC) have a high prevalence of comorbidities. However, the prognostic impact of comorbidities in these patients is not well studied. We aimed to outline the comorbidity burden in UTUC patients and investigate its relationship with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). We retrospectively reviewed the clinicopathological data of 409 non-metastatic UTUC patients who received radical nephroureterectomy between 2000 and 2015. The comorbidity burden was evaluated using the Adult Comorbidity Evaluation-27 (ACE-27). Kaplan-Meier survival analysis showed that high ACE-27 grade was significantly associated with worse PFS, CSS, and OS. In multivariate Cox regression and competing risk analyses, we found that ACE-27 grade, tumor stage, and tumor grade were independent prognosticators of OS, CSS, and PFS. We combined these three significant factors to construct a prognostic model for predicting clinical outcomes. A receiver operating characteristic curve revealed that our prognostic model had high predictive performance. The Harrel's concordance indices of this model for predicting OS, CSS, and PFS were 0.81, 0.85, and 0.85, respectively. The results suggest that the UTUC patient comorbidity burden (ACE-27) provides information on the risk for meaningful clinical outcomes of OS, CSS, and PFS.

Association of Warmer Weather and Infectious Complications Following Transrectal Ultrasound-Guided Prostate Biopsy.

The seasonal and meteorological factors in predicting infections after urological interventions have not been systematically evaluated. This study aimed to determine the seasonality and the effects of the weather on the risk and severity of infectious complications (IC) after a transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Using retrospectively collected data at the tertiary care hospital in Taiwan, we investigated the seasonal and meteorological differences in IC after TRUS-Bx. The IC included urinary tract infection (UTI), sepsis, and a positive culture finding (PCF). The severity was assessed on the basis of the Common Terminology Criteria for Adverse Events grading system. The prevalences of the infectious complications (UTI, sepsis, PCF and grade ≥ 3 IC) were significantly higher in the summer than in the winter. Monthly temperature and average humidity were significant factors for IC. After adjusting the demographic factors, multivariate regression revealed that UTI, sepsis, PCF, and grade ≥ 3 IC increased by 12.1%, 16.2%, 21.3%, and 18.6% for every 1 °C increase in the monthly average temperature, respectively (UTI: p = 0.010; sepsis: p = 0.046; PCF: p = 0.037; grade ≥ 3 IC: p = 0.021). In conclusion, the development and severity of IC after TRUS-Bx had significant seasonality. These were dose-dependently associated with warmer weather. Infectious signs after TRUS-Bx should be monitored more closely and actively during warm weather.

Congenital collagenopathies increased the risk of inguinal hernia developing and repair: analysis from a nationwide population-based cohort study.

Herein, we aimed to explore whether male patients with congenital collagen diseases had a higher risk of inguinal herniation than patients without these diseases. Data were retrospectively collected from the National Health Insurance Research Database of Taiwan. The study cohort included 1,801 male patients diagnosed with congenital collagen diseases based on the ICD-9 CM diagnostic codes; after propensity score matching, the control group comprised 6,493 men without congenital collagen diseases. The primary endpoint was inguinal hernia repair during the observation period. During a median follow-up period of 133.9 months, the risk of inguinal herniation in the collagen group was significantly higher than that in the control group (HR = 2.237, 95% CI 1.646-3.291, p < 0.001). This phenomenon was observed in patients younger than 18 years (HR: 3.040, 95% CI 1.819-5.083, p < 0.001) and in those aged 18-80 years (HR: 1.909, 95% CI 1.186-3.073, p < 0.001). Asian men with congenital collagen diseases are at a high risk of developing inguinal hernias, regardless of age. Detailed physical examination and patient education should be performed for these patients to prevent inguinal herniation.

MicroRNA-375-3p Suppresses Upper Tract Urothelial Carcinoma Cell Migration and Invasion via Targeting Derlin-1.

Little is known regarding the molecular characterization of upper tract urothelial carcinoma (UTUC). Novel therapeutic targets and prognostic predictors are imminent. In the present study, we aim to examine the oncogenic function and molecular mechanism of Derlin-1 in UTUC. Derlin-1 overexpression is significantly associated with poor prognosis in patients with UTUC. In vitro, knockdown or over-expression of Derlin-1 markedly regulated UTUC cell invasion and migration. We further discovered miR-375-3p suppresses cell invasion and migration by inversely regulating Derlin-1 and blocking EMT in UTUC cells. Taking this together, miR-375-3p functions as a tumor suppressive microRNA by directly targeting Derlin-1 and blocking epithelial-mesenchymal transition (EMT) in UTUC.

Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients.

Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine's effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-ß-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.