A case report on the atypical metastatic pathway of prostate cancer to the kidney and stomach.

Prostate cancer rarely metastasizes to the stomach and kidneys. We report a 73-year-old male with such spread, highlighting significant clinical challenges. Initially diagnosed via biopsy and imaging, he received hormone therapy and cytoreductive radical prostatectomy. Despite initial management, the cancer progressed to metastatic castration-resistant prostate cancer, with gastric and renal metastases confirmed by imaging and biopsy. This case emphasizes the need for awareness of rare metastatic sites, comprehensive diagnostic evaluations, and further research into these atypical metastases to improve patient outcomes and develop better treatment strategies for managing advanced prostate cancer effectively.

ESM1 facilitates the EGFR/HER3-triggered epithelial-to-mesenchymal transition and progression of gastric cancer via modulating interplay between Akt and angiopoietin-2 signaling.

Gastric cancer (GC) poses global challenges due to its difficult early diagnosis and drug resistance, necessitating the identification of early detection markers and understanding of oncogenic pathways for effective GC therapy. Endothelial cell-specific molecule 1 (ESM1), a secreted glycoprotein, is elevated in various cancers, but its role in GC remains controversial. In our study, ESM1 was elevated in GC tissues, and its concentration was correlated with progression and poorer patient prognosis in independent cohorts. Functionally, ESM1 expression promoted proliferation, anoikis resistance, and motility of GC cells, as well as tumor growth in PDOs and in GC xenograft models. Mechanistically, ESM1 expression triggered the epithelial-to-mesenchymal transition (EMT) of GC cells by enhancing epidermal growth factor receptor (EGFR)/human EGFR 3 (HER3) association and activating the EGFR/HER3-Akt pathway. Additionally, angiopoietin-2 (ANGPT2) was found to be highly correlated with ESM1 and interplayed with Akt to induce the EMT and cancer progression. Use of a signal peptide deletion mutant (ESM1-19del) showed that the secreted form of ESM1 is crucial for its protumorigenic effects by activating the EGFR/HER3-Akt/ANGPT2 pathway to promote the EMT. Patients with high levels of both ESM1 and ANGPT2 had the poorest prognoses. Furthermore, therapeutic peptides successfully inhibited ESM1's induction of the aforementioned signals and motility of GC cells. ESM1's oncogenic role in GC involves activating the EGFR/HER3-Akt/ANGPT2 pathway, presenting a potential therapeutic target for GC.

MicroRNA Signature in an In Vitro Keratinocyte Model of Diabetic Wound Healing.

Treating diabetic wounds effectively remains a significant clinical challenge. Emerging studies suggest that microRNAs (miRNAs) play crucial roles in various physiological and pathological processes and hold promise as therapeutic tools. This study investigates the miRNA expression profile in keratinocytes using a cell model of diabetic wounds. Microarray analysis revealed that 43 miRNAs from wounded keratinocytes incubated under diabetic conditions (high glucose/hypoxia) exhibited a two-fold change in expression compared to those incubated under normal conditions (low glucose/normoxia). Quantitative RT-PCR confirmed significant differences in the expression of eight miRNAs, with miR-3138 and miR-3679-5p being further analyzed for their roles in keratinocyte migration. Transfection with a miR-3138 mimic and a miR-3679-5p inhibitor indicated that upregulation of miR-3138 and downregulation of miR-3679-5p enhance keratinocyte migration in both normal and diabetic wounds. Pathway and gene ontology (GO) analyses identified potential pathways and functional annotations associated with miR-3138 and miR-3679-5p in diabetic wound healing. Potential human gene targets of miR-3138 and miR-3679-5p were predicted using a three-way comparison of the TargetScan, miRDB, and DIANA databases. This study elucidates the miRNA expression signature of human keratinocytes in a diabetes-like environment, providing deeper insights into the pathogenesis of diabetic wounds.

Concurrent occurrence of adenocarcinoma and urothelial carcinoma of the prostate gland: A case report.

BACKGROUND: Adenocarcinoma is the most common subtype of prostate cancer. Prostatic urothelial carcinoma (UC) typically originates from the prostatic urethra. The concurrent occurrence of adenocarcinoma and UC of the prostate gland is uncommon. CASE SUMMARY: We present the case of an 82-year-old male patient with simultaneous adenocarcinoma and UC of the prostate gland. The patient underwent a transrectal ultrasound-guided biopsy, and the pathology test revealed UC. Subsequently, transurethral laser prostatectomy was performed, and the pathology test indicated adenocarcinoma of the prostate with a Gleason score of 3 + 4 and high-grade UC. Therefore, the patient was treated with androgen deprivation therapy, systemic chemotherapy, and immunotherapy. Magnetic resonance imaging performed during follow-up revealed a prostate tumor classified as cT2cN1M0, stage IVA. Therefore, the patient underwent robotic-assisted radical prostatectomy and bilateral pelvic lymph node dissection. The final pathology test of the prostate gland revealed acinar-type adenocarcinoma, Gleason pattern 4 + 3, pT2N0M0, and high-grade UC. The patient regularly presented to the clinic for postoperative follow-up evaluations. He did not experience any urinary discomfort. CONCLUSION: According to our literature review, this is the first reported case of coexisting adenocarcinoma and UC of the prostate gland.

Effect of nocturia in patients with different severity of obstructive sleep apnea on polysomnography: A retrospective observational study.

Objective: Obstructive sleep apnea (OSA) is one of the etiologies of nocturia. We analyzed polysomnography (PSG) results to determine correlated factors related to nocturia in OSA patients with different severity. Methods: Patients with suspected OSA were examined using PSG. They were divided into two groups based on the presence of nocturia. Nocturia was defined as a patient who needed to void at least once. Apnea-hypopnea index (AHI) was employed to classify patients according to degrees of severity: AHI<5 events/h, 5 events/h≤AHI<15 events/h, 15 events/h≤AHI<30 events/h, and AHI≥30 events/h, defined as normal, mild OSA, moderate OSA, and severe OSA, respectively. Demographic variables, PSG parameters, International Prostate Symptom Scores (IPSSs), and quality of life scores due to urinary symptoms were analyzed. Results: In total 140 patients, 114 patients had OSA (48 had mild OSA; 34 had moderate OSA; and 32 had severe OSA) and 107 patients had nocturia. The total IPSS was significantly higher in nocturia patients in all groups except the group of severe OSA patients. With the increasing severity of OSA, more correlated factors related to nocturia were determined. In mild OSA patients, nocturia related to increased age (p=0.025), minimum arterial blood oxygenation saturation (p=0.046), and decreased AHI of non-rapid eye movement (p=0.047), AHI of total sleep time (p=0.010), and desaturation index (p=0.012). In moderate OSA patients, nocturia related to increased age (p<0.001), awake time (p=0.025), stage 1 sleep (p=0.033), and sleep latency (p=0.033), and decreased height (p=0.044), weight (p=0.025), and sleep efficiency (p=0.003). In severe OSA patients, nocturia related to increased weight (p=0.011), body mass index (p=0.009), awake time (p=0.008), stage 1 sleep (p=0.040), arousal number (p=0.030), arousal index (p=0.013), periodic limb movement number (p=0.013), and periodic limb movement index (p=0.004), and decreased baseline arterial blood oxygenation saturation (p=0.046). Conclusion: Our study revealed that there were more correlated factors related to nocturia with increasing severity of OSA. This study helps in clinical education and treatment for OSA patients with different severity.

Evaluating Urine Cytology Slide Digitization Efficiency: A Comparative Study Using an Artificial Intelligence-Based Heuristic Scanning Simulation and Multiple Z-Plane Scanning.

INTRODUCTION: Digitizing cytology slides presents challenges because of their three-dimensional features and uneven cell distribution. While multi-Z-plane scan is a prevalent solution, its adoption in clinical digital cytopathology is hindered by prolonged scanning times, increased image file sizes, and the requirement for cytopathologists to review multiple Z-plane images. METHODS: This study presents heuristic scan as a novel solution, using an artificial intelligence (AI)-based approach specifically designed for cytology slide scanning as an alternative to the multi-Z-plane scan. Both the 21 Z-plane scan and the heuristic scan simulation methods were used on 52 urine cytology slides from three distinct cytopreparations (Cytospin, ThinPrep, and BD CytoRich™ [SurePath]), generating whole-slide images (WSIs) via the Leica Aperio AT2 digital scanner. The AI algorithm inferred the WSI from 21 Z-planes to quantitate the total number of suspicious for high-grade urothelial carcinoma or more severe cells (SHGUC+) cells. The heuristic scan simulation calculated the total number of SHGUC+ cells from the 21 Z-plane scan data. Performance metrics including SHGUC+ cell coverage rates (calculated by dividing the number of SHGUC+ cells identified in multiple Z-planes or heuristic scan simulation by the total SHGUC+ cells in the 21 Z-planes for each WSI), scanning time, and file size were analyzed to compare the performance of each scanning method. The heuristic scan's metrics were linearly estimated from the 21 Z-plane scan data. Additionally, AI-aided interpretations of WSIs with scant SHGUC+ cells followed The Paris System guidelines and were compared with original diagnoses. RESULTS: The heuristic scan achieved median SHGUC+ cell coverage rates similar to 5 Z-plane scans across three cytopreparations (0.78-0.91 vs. 0.75-0.88, p = 0.451-0.578). Notably, it substantially reduced both scanning time (137.2-635.0 s vs. 332.6-1,278.8 s, p < 0.05) and image file size (0.51-2.10 GB vs. 1.16-3.10 GB, p < 0.05). Importantly, the heuristic scan yielded higher rates of accurate AI-aided interpretations compared to the single Z-plane scan (62.5% vs. 37.5%). CONCLUSION: We demonstrated that the heuristic scan offers a cost-effective alternative to the conventional multi-Z-plane scan in digital cytopathology. It achieves comparable SHGUC+ cell capture rates while reducing both scanning time and image file size, promising to aid digital urine cytology interpretations with a higher accuracy rate compared to the conventional single (optimal) plane scan. Further studies are needed to assess the integration of this new technology into compatible digital scanners for practical cytology slide scanning.

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.

Lactoferrin as a therapeutic agent for attenuating hepatic stellate cell activation in thioacetamide-induced liver fibrosis.

Liver fibrosis is a chronic liver disease caused by prolonged liver injuries. Excessive accumulation of extracellular matrix replaces the damaged hepatocytes, leading to fibrous scar formation and fibrosis induction. Lactoferrin (LF) is a glycoprotein with a conserved, monomeric signal polypeptide chain, exhibiting diverse physiological functions, including antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and antitumoral activities. Previous study has shown LF's protective role against chemically-induced liver fibrosis in rats. However, the mechanisms of LF in liver fibrosis are still unclear. In this study, we investigated LF's mechanisms in thioacetamide (TAA)-induced liver fibrosis in rats and TGF-ß1-treated HSC-T6 cells. Using ultrasonic imaging, H&E, Masson's, and Sirius Red staining, we demonstrated LF's ability to improve liver tissue damage and fibrosis induced by TAA. LF reduced the levels of ALT, AST, and hydroxyproline in TAA-treated liver tissues, while increasing catalase levels. Additionally, LF treatment decreased mRNA expression of inflammatory factors such as Il-1ß and Icam-1, as well as fibrogenic factors including α-Sma, Collagen I, and Ctgf in TAA-treated liver tissues. Furthermore, LF reduced TAA-induced ROS production and cell death in FL83B cells, and decreased α-SMA, Collagen I, and p-Smad2/3 productions in TGF-ß1-treated HSC-T6 cells. Our study highlights LF's ability to ameliorate TAA-induced hepatocyte damage, oxidative stress, and liver fibrosis in rats, potentially through its inhibitory effect on HSC activation. These findings suggest LF's potential as a therapeutic agent for protecting against liver injuries and fibrosis.

Kefir peptides mitigate bleomycin-induced pulmonary fibrosis in mice through modulating oxidative stress, inflammation and gut microbiota.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and life-threatening lung disease with high mortality rates. The limited availability of effective drugs for IPF treatment, coupled with concerns regarding adverse effects and restricted responsiveness, underscores the need for alternative approaches. Kefir peptides (KPs) have demonstrated antioxidative, anti-inflammatory, and antifibrotic properties, along with the capability to modulate gut microbiota. This study aims to investigate the impact of KPs on bleomycin-induced pulmonary fibrosis. METHODS: Mice were treated with KPs for four days, followed by intratracheal injection of bleomycin for 21 days. Comprehensive assessments included pulmonary functional tests, micro-computed tomography (µ-CT), in vivo image analysis using MMPsense750, evaluation of inflammation- and fibrosis-related gene expression in lung tissue, and histopathological examinations. Furthermore, a detailed investigation of the gut microbiota community was performed using full-length 16 S rRNA sequencing in control mice, bleomycin-induced fibrotic mice, and KPs-pretreated fibrotic mice. RESULTS: In KPs-pretreated bleomycin-induced lung fibrotic mice, notable outcomes included the absence of significant bodyweight loss, enhanced pulmonary functions, restored lung tissue architecture, and diminished thickening of inter-alveolar septa, as elucidated by morphological and histopathological analyses. Concurrently, a reduction in the expression levels of oxidative biomarkers, inflammatory factors, and fibrotic indicators was observed. Moreover, 16 S rRNA sequencing demonstrated that KPs pretreatment induced alterations in the relative abundances of gut microbiota, notably affecting Barnesiella_intestinihominis, Kineothrix_alysoides, and Clostridium_viride. CONCLUSIONS: Kefir peptides exerted preventive effects, protecting mice against bleomycin-induced lung oxidative stress, inflammation, and fibrosis. These effects are likely linked to modifications in the gut microbiota community. The findings highlight the therapeutic potential of KPs in mitigating pulmonary fibrosis and advocate for additional exploration in clinical settings.

Cyclic increase in the ADAMTS1-L1CAM-EGFR axis promotes the EMT and cervical lymph node metastasis of oral squamous cell carcinoma.

The matrix metalloprotease A disintegrin and metalloprotease with thrombospondin motifs 1 (ADAMTS1) was reported to be involved in tumor progression in several cancer types, but its contributions appear discrepant. At present, the role of ADAMTS1 in oral squamous cell carcinoma (SCC; OSCC) remains unclear. Herein, The Cancer Genome Atlas (TCGA) database showed that ADAMTS1 transcripts were downregulated in head and neck SCC (HNSCC) tissues compared to normal tissues, but ADAMTS1 levels were correlated with poorer prognoses of HNSCC patients. In vitro, we observed that ADAMTS1 expression levels were correlated with the invasive abilities of four OSCC cell lines, HSC-3, SCC9, HSC-3M, and SAS. Knockdown of ADAMTS1 in OSCC cells led to a decrease and its overexpression led to an increase in cell-invasive abilities in vitro as well as tumor growth and lymph node (LN) metastasis in OSCC xenografts. Mechanistic investigations showed that the cyclic increase in ADAMTS1-L1 cell adhesion molecule (L1CAM) axis-mediated epidermal growth factor receptor (EGFR) activation led to exacerbation of the invasive abilities of OSCC cells via inducing epithelial-mesenchymal transition (EMT) progression. Clinical analyses revealed that ADAMTS1, L1CAM, and EGFR levels were all correlated with worse prognoses of HNSCC patients, and patients with ADAMTS1high/L1CAMhigh or EGFRhigh tumors had the shortest overall and disease-specific survival times. As to therapeutic aspects, we discovered that an edible plant-derived flavonoid, apigenin (API), drastically inhibited expression of the ADAMTS1-L1CAM-EGFR axis and reduced the ADAMTS1-triggered invasion and LN metastasis of OSCC cells in vitro and in vivo. Most importantly, API treatment significantly prolonged survival rates of xenograft mice with OSCC. In summary, ADAMTS1 may be a useful biomarker for predicting OSCC progression, and API potentially retarded OSCC progression by targeting the ADAMTS1-L1CAM-EGFR signaling pathway.

Comparative evaluation of slide scanners, scan settings, and cytopreparations for digital urine cytology.

Background: Acquiring well-focused digital images of cytology slides with scanners can be challenging due to the 3-dimensional nature of the slides. This study evaluates performances of whole-slide images (WSIs) obtained from 2 different cytopreparations by 2 distinct scanners with 3 focus modes. Methods: Fourteen urine specimens were collected from patients with urothelial carcinoma. Each specimen was equally divided into 2 portions, prepared with Cytospin and ThinPrep methods and scanned for WSIs using Leica (Aperio AT2) and Hamamatsu (NanoZoomer S360) scanners, respectively. The scan settings included 3 focus modes (default, semi-auto, and manual) for single-layer scanning, along with a manual focus mode for 21 Z-layers scanning. Performance metrics were evaluated including scanning success rate, artificial intelligence (AI) algorithm-inferred atypical cell numbers and coverage rate (atypical cell numbers in single or multiple Z-layers divided by the total atypical cell numbers in 21 Z-layers), scanning time, and image file size. Results: The default mode had scanning success rates of 85.7% or 92.9%, depending on the scanner used. The semi-auto mode increased success to 92.9% or 100%, and manual even further to 100%. However, these changes did not affect the standardized median atypical cell numbers and coverage rates. The selection of scanners, cytopreparations, and Z-stacking influenced standardized median atypical cell numbers and coverage rates, scanning times, and image file sizes. Discussion: Both scanners showed satisfactory scanning. We recommend using semi-auto or manual focus modes to achieve a scanning success rate of up to 100%. Additionally, a minimum of 9-layer Z-stacking at 1 µm intervals is required to cover 80% of atypical cells. These advanced focus methods do not impact the number of atypical cells or their coverage rate. While Z-stacking enhances the AI algorithm's inferred quantity and coverage rates of atypical cells, it simultaneously results in longer scanning times and larger image file sizes.

Theranostic Robot-Assisted Radical Prostatectomy: Things Understood and Not Understood.

OBJECTIVE: This study aimed to explore the benefits of theranostic robot-assisted radical prostatectomy (T-RARP) for clinically highly suspicious prostate cancer (PCa) without proven biopsies. MATERIAL AND METHODS: Between February 2016 and December 2020, we included men with clinically highly suspicious PCa in this study. They were assessed to have possible localized PCa without any initial treatments, and were categorized into previous benign biopsies or without biopsies. Furthermore, another group of malignant biopsies with RARP in the same time frame was adopted as the control group. The endpoints were to compare the oncological outcome and functional outcome between malignant biopsies with RARP and T-RARP. p < 0.05 was considered to be significant. RESULTS: We included 164 men with proven malignant biopsies treated with RARP as the control group. For T-RARP, we included 192 men. Among them, 129 were preoperatively benign biopsies, and 63 had no biopsies before T-RARP. Approximately 75% of men in the T-RARP group had malignant pathology in their final reports, and the other 25% had benign pathology. T-RARP provides several oncological advantages, such as a higher initial pathological T stage, lower Gleason grade, and lower odds of positive surgical margins. However, the biochemical recurrence rates were not significantly decreased. From our cohort, T-RARP (odds ratio with 95% confidence interval; erectile recovery: 3.19 (1.84-5.52), p < 0.001; continence recovery: 2.25 (1.46-3.48), p < 0.001) could result in better recovery of functional outcomes than malignant biopsies with RARP. CONCLUSIONS: For clinically highly suspicious PCa, T-RARP was able to detect around 75% of PCa cases and preserved their functional outcomes maximally. However, in 25% of men with benign pathology, approximately 6% would have incontinence and 10% would have erectile impairment. This part should be sufficiently informed of the potential groups considering T-RARP.

Robotic partial nephrectomy for renal tumor: The pentafecta outcomes of a single surgeon experience.

PURPOSE: This study investigated the oncological and functional surgical outcomes for patients with renal tumor who underwent robot-assisted partial nephrectomy (PN) by a single surgeon in Taiwan from 2006 to 2019. METHODS: This retrospective study assessed patients who underwent robot-assisted PN for renal tumor. Patient data were analyzed for age, sex, body mass index, operative time and total ischemic time, surgical margin (positive/negative), and surgical complications. To evaluate functional and oncological outcomes, achievement of trifecta, and pentafecta criteria was used. Trifecta criteria were defined as a negative surgical margin, no postoperative complications, warm ischemia time <25 min. Pentafecta criteria were the trifecta criteria, >90% preservation of estimated glomerular filtration rate (eGFR) preservation, and no stage progression of chronic kidney disease at 1-year follow-up. RESULTS: Of 101 patients who received robot-assisted PN, the most common type of renal tumor was clear cell renal cell carcinoma (RCC) (38%), followed by angiomyolipoma (26%). Patient characteristics were mean age 54.59 ± 13.8 years; mean RENAL Nephrometry score 6.63 ± 2.16; mean operative time 102.34 ± 50.06 min; and warm ischemia time 20.01 ± 14.12 min. The mean eGFR was 104.43 ± 31.73 mL/min/1.73 m2 preoperatively and 89.39 ± 32.3 mL/min/1.73 m2 postoperatively. Pathologic evaluation showed malignant tumors in 57 patients, among whom achievement of trifecta criteria occurred for 39 (68.42%) and pentafecta criteria for 18 (31.57%). Operation time was the only predictor for pentafecta achievement. CONCLUSION: Robotic PN is a safe and effective approach for patients with renal tumor that can preserve most renal function and achieve oncological control. Pentafecta criteria can be used to more clearly define the surgical outcome of RAPN.

Robot-assisted radical prostatectomy using hugo RAS system: The pioneer experience in Taiwan and Northeast Asia.

BACKGROUND: Among the novel robotic platforms, the Hugo RAS system is the second most studied platform, next to the da Vinci system, and we aim to address our experiences in radical prostatectomy (RP) with the Hugo RAS system. METHODS: We recorded our first 12 cases of prostate cancer undergoing RP with the Hugo RAS system. The median console time was 145 min and median hospital stay was 7 days. Hedge' g was applied to search for the cut-off case in four parameters in surgeries. RESULTS: Pre-console preparation was significantly improved after the first seven cases, and the console time was remarkably shortened after the first two cases. The intraoperative pause for trouble shooting was remarkably shortened after the first three cases. CONCLUSIONS: We found that RP with the Hugo RAS system was feasible, and the learning curve was short as surgeons may benefit from the previous experience with the da Vinci system.

The RNA-binding protein KSRP aggravates malignant progression of clear cell renal cell carcinoma through transcriptional inhibition and post-transcriptional destabilization of the NEDD4L ubiquitin ligase.

BACKGROUND: KH-type splicing regulatory protein (KHSRP, also called KSRP), a versatile RNA-binding protein, plays a critical role in various physiological and pathological conditions through modulating gene expressions at multiple levels. However, the role of KSRP in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: KSRP expression was detected by a ccRCC tissue microarray and evaluated by an in silico analysis. Cell loss-of-function and gain-of-function, colony-formation, anoikis, and transwell assays, and an orthotopic bioluminescent xenograft model were conducted to determine the functional role of KRSP in ccRCC progression. Micro (mi)RNA and complementary (c)DNA microarrays were used to identify downstream targets of KSRP. Western blotting, quantitative real-time polymerase chain reaction, and promoter- and 3-untranslated region (3'UTR)-luciferase reporter assays were employed to validate the underlying mechanisms of KSRP which aggravate progression of ccRCC. RESULTS: Our results showed that dysregulated high levels of KSRP were correlated with advanced clinical stages, larger tumor sizes, recurrence, and poor prognoses of ccRCC. Neural precursor cell-expressed developmentally downregulated 4 like (NEDD4L) was identified as a novel target of KSRP, which can reverse the protumorigenic and prometastatic characteristics as well as epithelial-mesenchymal transition (EMT) promotion by KSRP in vitro and in vivo. Molecular studies revealed that KSRP can decrease NEDD4L messenger (m)RNA stability via inducing mir-629-5p upregulation and directly targeting the AU-rich elements (AREs) of the 3'UTR. Moreover, KSRP was shown to transcriptionally suppress NEDD4L via inducing the transcriptional repressor, Wilm's tumor 1 (WT1). In the clinic, ccRCC samples revealed a positive correlation between KSRP and mesenchymal-related genes, and patients expressing high KSRP and low NEDD4L had the worst prognoses. CONCLUSION: The current findings unveil novel mechanisms of KSRP which promote malignant progression of ccRCC through transcriptional inhibition and post-transcriptional destabilization of NEDD4L transcripts. Targeting KSRP and its pathways may be a novel pharmaceutical intervention for ccRCC.

Efficacy and safety of once-daily prolonged-release tacrolimus versus twice-daily tacrolimus in kidney transplant recipients: A meta-analysis and trial sequential analysis.

BACKGROUND: Kidney transplantation is the most important treatment for end-stage renal disease. Immunosuppressive therapies can prevent acute rejection for kidney transplant recipients. Tacrolimus is usually administered to prevent graft rejection after transplantation. Previous studies have indicated that once-daily tacrolimus may improve medication adherence. Therefore, this meta-analysis aimed to compare clinical outcomes between once-daily and twice-daily tacrolimus in de novo renal transplant patients. METHODS: Eligible studies were identified from the Cochrane Library Database, PubMed, and Embase until July 2022. Those randomized controlled trials (RCTs) evaluating once-daily versus twice-daily tacrolimus formulations in de novo renal transplantation were included. A summary risk ratio (RR) and standardized mean difference (SMD) with the 95% confidence interval (CI) were estimated using a random-effects model. RESULTS: In total, nine RCTs were included. There were no differences in biopsy-confirmed acute rejection rates between patients with once-daily and those with twice-daily tacrolimus (RR, 0.91; 95% CI, 0.73-1.13) in 12 months. Regarding renal function, there was no significant difference between the once-daily and twice-daily tacrolimus groups (SMD, -0.03; 95% CI, -0.12 to 0.07). In addition, the risk of graft failure, death, and adverse events in the first year was similar for the once-daily and twice-daily tacrolimus groups. CONCLUSION: Our major findings suggest that de novo renal transplantation recipients receiving once-daily tacrolimus immediately after transplantation have comparable efficacy and safety with those recipients who received twice-daily tacrolimus. Therefore, once-daily tacrolimus medication can be an alternative for de novo renal transplantation recipients.

Synchronized extracorporeal shockwave lithotripsy may still affect the heart: a case report of perioperative ST-segment elevation myocardial infarction.

Extracorporeal shockwave lithotripsy (ESWL) is widely used as a primary treatment for urolithiasis and is performed as an elective outpatient surgical procedure because of its ease of use. However, patients undergoing this treatment rarely develop cardiac complications. In this article, we present the case of a 45-year-old male patient who presented with ST-elevation myocardial infarction during ESWL. Moreover, atypical symptoms and electrocardiogram patterns were recognized by the nursing staff. Early primary evaluation and intervention resulted in favorable outcomes along with patent coronary artery flow following stent placement for stenosis, and no complications were noted.

One-Step Robot-Assisted Complete Urinary Tract Extirpation in Man with End-Stage Renal Disease on Dialysis: The First Case Report.

Urothelial carcinoma (UC) could be observed in urinary bladder (UBUC) and upper urinary tracts (UTUC). In the National Comprehensive Cancer Network guidelines for bladder cancer, extirpative surgery is indicated in certain cases. However, some extreme cases might also need the extirpation of the majority of the urinary tract, which is called complete urinary tract extirpation (CUTE). We present a patient diagnosed with high-grade UBUC and UTUC. He underwent dialysis for end-stage renal disease (ESRD) at the same time. Considering his non-functional kidneys and removing his high-risk urothelium at the same time, we performed robot-assisted CUTE to extirpate both his upper urinary tracts, urinary bladder, and prostate. In our experience, the console time was not significantly elongated, and the perioperative course was uneventful. To our knowledge, this is the first case report adopting a robotic system in such an extreme case. We conclude that robot-assisted CUTE is worth further study regarding its oncological survival outcomes and perioperative safety in patients with ESRD on dialysis.

Incorporating VR-RENDER Fusion Software in Robot-Assisted Partial Prostatectomy: The First Case Report.

Currently, the active surveillance of men with favorable intermediate-risk localized prostate cancer (PCa) is a longstanding controversy, in terms of their oncological outcomes, and radical prostatectomy would constitute a similar concern of overtreatment, regarding its functional outcomes. Thus, focal therapy could be considered in men belonging to favorable intermediate-risk group. Among all focal therapies, high-intensity focused ultrasound (HIFU) was the most studied methodology in clinical trials. Although HIFU provided better functional outcomes than radical prostatecomy, the oncological outcomes were inferior in men with intermediate-risk localized PCa. Two articles have been published discussing the feasibility and clinical outcomes of robot-assisted partial prostatectomy (RAPP), and both the functional and oncological outcomes were superior than those with HIFU. However, the rate of positive surgical margins (PSMs) was reported as high in the literature. Here, we present a case of favorable intermediate-risk localized PCa with an isolated tumor at the anterior apex. After reconstructing a personal three-dimensional (3D) image, we utilized it in a 3D image-guided precise excise, followed by intraoperative frozen specimen review. We found that this method may present a resolution to the high PSM rate documented in the current literature regarding RAPP. This method merits further study with a well-designed prospective study.

The Immunological Microenvironment and the Emerging Role of Stem Cells Therapy in Peyronie's Disease: A Systematic Narrative Review.

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.