Proteomic Identification of Small Extracellular Vesicle Proteins LAMB1 and Histone H4 for Prostate Cancer Diagnosis and Risk Stratification.

Diagnosis and stratification of prostate cancer (PCa) patients using the prostate-specific antigen (PSA) test is challenging. Extracellular vesicles (EVs), as a new star of liquid biopsy, has attracted interest to complement inaccurate PSA screening and invasiveness of tissue biopsy. In this study, a panel of potential small EV (sEV) protein biomarkers is identified from PCa cell lines using label-free LC-MS/MS proteomics. These biomarkers underwent further validation with plasma and urine samples from different PCa stages through parallel reaction monitoring-based targeted proteomics, western blotting, and ELISA. Additionally, a tissue microarray containing cancerous and noncancerous tissues is screened to provide additional evidence of selected sEV proteins associated with cancer origin. Results indicate that sEV protein LAMB1 is highly expressed in human plasma of metastatic PCa patients compared with localised PCa patients and control subjects, while sEV protein Histone H4 is highly expressed in human urine of high-risk PCa patients compared to low-risk PCa patients and control subjects. These two sEV proteins demonstrate higher specificity and sensitivity than the PSA test and show promise for metastatic PCa diagnosis, progression monitoring, and risk stratification.

Identification of novel protein biomarkers from the blood and urine for the early diagnosis of bladder cancer via proximity extension analysis.

BACKGROUND: Bladder cancer (BC) is a very common urinary tract malignancy that has a high incidence and lethality. In this study, we identified BC biomarkers and described a new noninvasive detection method using serum and urine samples for the early detection of BC. METHODS: Serum and urine samples were retrospectively collected from patients with BC (n = 99) and healthy controls (HC) (n = 50), and the expression levels of 92 inflammation-related proteins were examined via the proximity extension analysis (PEA) technique. Differential protein expression was then evaluated by univariate analysis (p < 0.05). The expression of the selected potential marker was further verified in BC and adjacent tissues by immunohistochemistry (IHC) and single-cell sequencing. A model was constructed to differentiate BC from HC by LASSO regression and compared to the detection capability of FISH. RESULTS: The univariate analysis revealed significant differences in the expression levels of 40 proteins in the serum (p < 0.05) and 17 proteins in the urine (p < 0.05) between BC patients and HC. Six proteins (AREG, RET, WFDC2, FGFBP1, ESM-1, and PVRL4) were selected as potential BC biomarkers, and their expression was evaluated at the protein and transcriptome levels by IHC and single-cell sequencing, respectively. A diagnostic model (a signature) consisting of 14 protein markers (11 in serum and three in urine) was also established using LASSO regression to distinguish between BC patients and HC (area under the curve = 0.91, PPV = 0.91, sensitivity = 0.87, and specificity = 0.82). Our model showed better diagnostic efficacy than FISH, especially for early-stage, small, and low-grade BC. CONCLUSION: Using the PEA method, we identified a panel of potential protein markers in the serum and urine of BC patients. These proteins are associated with the development of BC. A total of 14 of these proteins can be used to detect early-stage, small, low-grade BC. Thus, these markers are promising for clinical translation to improve the prognosis of BC patients.

Slightly photo-crosslinked chitosan/silk fibroin hydrogel adhesives with hemostasis and anti-inflammation for pro-healing cyclophosphamide-induced hemorrhagic cystitis.

Cyclophosphamide is commonly used in the treatment of various cancers and autoimmune diseases, while concurrently imposing substantial toxicity on the bladder, frequently manifesting hemorrhagic cystitis. Intravesical interventions, such as hyaluronic acid supplementation, present a therapeutic strategy to reinstate bladder barrier function and alleviate the effects of metabolic toxicants. However, it remains a great challenge to achieve efficient cyclophosphamide-induced hemorrhagic cystitis (CHC) management with accelerated tissue repair owing to the low wet-adhesion, poor hemostasis, and acute inflammatory responses. To address these issues, a hemostatic and anti-inflammatory hydrogel adhesive of chitosan methylacryloyl/silk fibroin methylacryloyl (CHMA/SFMA) is developed for promoting the healing of CHC. The obtained hydrogels show a high adhesive strength of 26.21 N/m with porcine bladder, facilitating the rapid hemostasis within 15 s, and reinstate bladder barrier function. Moreover, this hydrogel adhesive promotes the proliferation and aggregation of SV-HUC-1 and regulates macrophage polarization. Implanting the hydrogels into CHC bladders of a SD rat model, they not only can be completely biodegraded in 14 days, but also effectively control hematuria and inflammation, and accelerate angiogenesis, thereby significantly promote the healing of bladder injury. Overall, CHMA/SFMA hydrogels exhibit rapid hemostasis for treating CHC and accelerate muscle tissue repair via angiogenesis and inflammation amelioration, which may provide a new path for managing severe hemorrhagic cystitis in the clinics.

Construction of a layer-by-layer self-assembled rosemarinic acid delivery system on the surface of CFRPEEK implants for enhanced anti-inflammatory and osseointegration activities.

Carbon fiber-reinforced polyether ether ketone (CFRPEEK) implants have attracted widespread attention in the field of clinical bone defect repair. However, the surface bioinertness confines the application of CFRPEEK implants. Inspired by the study of rosmarinic acid (RA)-promoted osteogenic differentiation, a self-assembly surface modification method based on electrostatic interactions, involving deposition of sodium carboxymethyl cellulose/chitosan and rosmarinic acid layer by layer on the surface of poly-L-lysine modified hydroxy CFRPEEK (SCPP/CC5@RA), is proposed to introduce RA on the surface of CFRPEEK for bioactivation. After layer-by-layer self-assembly (LBL), the surface of SCPP/CC5@RA exhibits weak electrophoresis (11.43 eV), suitable hydrophilicity, and bioactivity. The results of in vitro studies indicate that the RA release behavior of SCPP/CC5@RA effectively regulates the immune-inflammatory response and promotes the differentiation of osteoblasts. The rapid release of RA (0.17 µg mL-1) in the initial stage can downregulate the secretion of inflammation-related cytokines and significantly reduce oxidative stress levels; the sustained release of RA (0.06 µg mL-1) in the late stage can upregulate the expression of osteogenesis-related genes and induce mineralization of osteoblasts. Moreover, the rabbit tibia defect model demonstrates that the LBL technique can enhance the osseointegration of CFRPEEK implants. Compared with the control group, the bone trabecular thickness of the SCPP/CC5@RA group increases by 1.36 times, and the maximum pushing force increases by 2.67 times. In summary, this study provides a promising LBL based RA delivery system for the development of a dual-functional CFRPEEK implant in the field of bone implant biomaterials.

Prostate cancer-derived small extracellular vesicle proteins: the hope in diagnosis, prognosis, and therapeutics.

Current diagnostic tools for prostate cancer (PCa) diagnosis and risk stratification are insufficient. The hidden onset and poor efficacy of traditional therapies against metastatic PCa make this disease a heavy burden in global men's health. Prostate cancer-derived extracellular vesicles (PCDEVs) have garnered attention in recent years due to their important role in communications in tumor microenvironment. Recent advancements have demonstrated PCDEVs proteins play an important role in PCa invasion, progression, metastasis, therapeutic resistance, and immune escape. In this review, we briefly discuss the applications of sEV proteins in PCa diagnosis and prognosis in liquid biopsy, focus on the roles of the PCa-derived small EVs (sEVs) proteins in tumor microenvironment associated with cancer progression, and explore the therapeutic potential of sEV proteins applied for future metastatic PCa therapy.

Pelvic drain placement after robot-assisted radical prostatectomy: meta-analysis.

BACKGROUND: It is not clear whether the routine placement of a pelvic drain after robot-assisted radical prostatectomy is a necessity. The aim of this study was to investigate this through a meta-analysis of RCTs and non-randomized studies. METHODS: A search was performed in PubMed/MEDLINE, Embase, the Cochrane Library, and the Web of Science, up to 9 March 2023, for clinical trials comparing no drain with pelvic drain placement for patients with prostate cancer after robot-assisted radical prostatectomy. Two researchers independently conducted literature screening, data extraction, and quality assessment. A random-effect model was assumed for all analyses. The Cochrane Collaboration's risk-of-bias tool was used to evaluate the methodological quality of RCTs and, for non-randomized studies, the ROBINS-I tool was used (where ROBINS-I stands for Risk Of Bias In Non-randomized Studies - of Interventions). This meta-analysis was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42023406429). RESULTS: A total of six studies with 1480 patients were included in the meta-analysis. Both the meta-analysis of RCTs and the meta-analysis of non-randomized studies showed that patients without drains had a similar estimated blood loss (mean difference 40.49 ml, 95% c.i. -59.75 to 140.74 ml, P = 0.430, and mean difference -14.20 ml, 95% c.i. -32.26 to 3.87 ml, P = 0.120 respectively), overall complication rate (OR 0.60, 95% c.i. 0.35 to 1.04, P = 0.070, and OR 0.90, 95% c.i. 0.59 to 1.39, P = 0.640 respectively), Clavien-Dindo grade I-II complication rate (OR 0.62, 95% c.i. 0.34 to 1.13, P = 0.120, and OR 0.83, 95% c.i. 0.28 to 2.51, P = 0.750 respectively), Clavien-Dindo grade III-V complication rate (OR 0.60, 95% c.i. 0.10 to 3.69, P = 0.590, and OR 0.92, 95% c.i. 0.25 to 3.39, P = 0.900 respectively), and duration of hospital stay (mean difference -0.08 days, 95% c.i. -0.45 to 0.29 days, P = 0.670, and mean difference -0.64 days, 95% c.i. -2.67 to 1.39 days, P = 0.540 respectively) compared with routinely drained patients. Meta-analysis of non-randomized studies revealed that the duration of operation for patients without drains was shorter than that for patients with drains (mean difference -34.88 min, 95% c.i. -43.58 to -26.18 min, P < 0.001), but the meta-analysis of RCTs indicated that there was no significant difference between the two groups (mean difference -7.64 min, 95% c.i. -15.61 to 0.32 min, P = 0.060). CONCLUSION: The intraoperative and postoperative outcomes of patients without drains were not inferior to those of patients with drains. In selected patients, pelvic drains can be omitted after robot-assisted radical prostatectomy.

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.

Construction of Multifunctional Zinc Ion Sustained-Release Biocoating on the Surface of Carbon Fiber Reinforced Polyetheretherketone with Enhanced Anti-inflammatory Activity, Angiogenesis, and Osteogenesis.

Current treatments of carbon fiber-reinforced polyetheretherketone (CFRPEEK) as orthopedic implants remain unsatisfactory due to the bioinert surface. The multifunctionalization of CFRPEEK, which endows it with regulating the immune inflammatory response, promoting angiogenesis, and accelerating osseointegration, is critical to the intricate bone healing process. Herein, a multifunctional zinc ion sustained-release biocoating, consisting of a carboxylated graphene oxide, zinc ion, and chitosan layer, covalently grafts on the surface of amino CFRPEEK (CP/GC@Zn/CS) to coordinate with the osseointegration process. The release behavior of zinc ions theoretically conforms to the different demands in the three stages of osseointegration, including the burst release of zinc ions in the early stage (7.27 µM, immunomodulation), continuous release in the middle stage (11.02 µM, angiogenesis), and slow release in the late stage (13.82 µM, osseointegration). In vitro assessments indicate that the multifunctional zinc ion sustained-release biocoating can remarkably regulate the immune inflammatory response, decrease the oxidative stress level, and promote angiogenesis and osteogenic differentiation. The rabbit tibial bone defect model further confirms that, compared to the unmodified group, the bone trabecular thickness of the CP/GC@Zn/CS group increases 1.32-fold, and the maximum push-out force improves 2.05-fold. In this study, a multifunctional zinc ion sustained-release biocoating constructed on the surface of CFRPEEK that conforms to the requirements of different osseointegration stages can be an attractive strategy for the clinical application of inert implants.

Ag NC and Ag NP/PorC Film-Based Surface-Enhanced Raman Spectroscopy-Type Immunoassay for Ultrasensitive Prostate-Specific Antigen Detection.

Surface-enhanced Raman scattering (SERS) is a spectral detection technology with high sensitivity and detectivity and can be used to detect the fingerprint information of the molecules with ultralow concentration. Herein, a kind of immunostructure constructed by Ag nanoparticle/porous carbon (Ag NP/PorC) films as the immunosubstrate and Ag NCs as the immunoprobes was presented for ultralow level prostate-specific antigen (PSA) detection. Experimentally, the Ag NP/PorC film was first prepared with a facile method by carbonizing the gelatin-AgNO3 film in air, and Ag NCs were synthesized by the hydrothermal method. Then, the Ag NP/PorC film was modified by PSA antibodies as the substrate, while Ag NCs were decorated by R6G and PSA antibodies for probes. The sandwiched SERS detection embodiment was constructed by the immunoreaction between the PSA and PSA antibody predecorated on the substrate and probes. Our results show that the proposed SERS-type immunoassay is highly sensitive and selective to a wide range of PSA concentrations from 10-5 to 10-12 g/mL. Thereafter, it was also implemented to detect the PSA level in human serum, and the results successfully reproduce the PSA levels as those measured by the chemiluminescence method with a recovery rate above 90%. All in all, this SERS-type immunoassay provides a promising method for the early diagnosis of prostate cancer.

Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle-invasive bladder cancer: A multi-center, single-arm, phase 2 study.

BACKGROUND: Neoadjuvant chemotherapy followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). However, treatment outcomes are suboptimal. Camrelizumab, a PD-1 blockade, has shown benefits in several tumors. This study aimed to investigate the efficacy and safety of neoadjuvant camrelizumab in combination with gemcitabine plus cisplatin (GC) followed by RC for MIBC patients. METHODS: This was a multi-center, single-arm study that enrolled MIBC patients with a clinical stage of T2-4aN0-1M0, and scheduled for RC. Patients received three 21-day cycles of camrelizumab 200 mg on day 1, gemcitabine 1000 mg/m2 on day 1 and 8, and cisplatin 70 mg/m2 on day 2, followed by RC. The primary endpoint was pathologic complete response (pCR, pT0N0). RESULTS: From May 2020 to July 2021, 43 patients were enrolled and received study medications at nine centers in China. Three of them were deemed ineligible and excluded from efficacy analysis but included in safety analysis. In total 10 patients were unevaluable as they declined RC (two due to adverse events [AEs] and eight due to patient's willingness). Among 30 evaluable patients, 13 patients (43.3%) achieved pCR, and 16 patients (53.3%) achieved pathologic downstaging. No AEs leading to death were observed. The most common AEs were anemia (69.8%), decreased white blood cell count (65.1%), and nausea (65.1%). Immune-related AEs were all grade 1 or 2. Pathologic response was not correlated with PD-L1 expression status or tumor mutation burden. Individual genes as a biomarker for pathologic response were not identified. CONCLUSIONS: Neoadjuvant treatment with camrelizumab and GC regimen demonstrated preliminary anti-tumor activity for MIBC patients with manageable safety profiles. The study met its primary endpoint, and the following randomized trial is ongoing.

Quantification of underivatized amino acids in solid beverages using high-performance liquid chromatography and a potentiometric detector.

The simultaneous quantification of amino acids (AAs) in solid beverages without prior derivatization was explored by high-performance liquid chromatography (HPLC) coupled to a potentiometric detector. Included were threonine, leucine, methionine, phenylalanine, and histidine. The potentiometric detector was made consisting of a copper(II)-selective electrode based on a polyvinyl chloride (PVC) membrane, and the potential changes in the detector were determined according to the coordination interactions between cupric copper ions released from the inner filling solution of the electrode and AAs. Conditions were optimized for effective separation and sensitive detection. Fundamental characteristics such as linearity, limits of detection, limits of quantitation, accuracy, precision, and robustness were validated experimentally. The calibration curves showed a linear relationship between peak heights and the injection concentrations of the AAs. The detection limits down to the sub-micromolar range were achieved under isocratic conditions, outperforming ultraviolet detection. The copper(II)-selective electrode had a minimum lifetime of one month. Some real samples were examined to further demonstrate the feasibility of the proposed approach. The measurement results obtained by the present method were in good agreement with those obtained by the HPLC-mass spectrometry (MS), indicating that the combined HPLC-potentiometric method is a potential option for quantifying AAs.

Feasibilities and outcomes of patients treated with simultaneous prostate biopsy and general urological surgeries.

The present single-center retrospective clinical real-world study aimed to assess the feasibility and outcomes of patients who underwent simultaneous prostate biopsy and general urological surgeries. The medical records of 49 patients who underwent prostate biopsy and general urological surgeries simultaneously from October 2016 to June 2019 were retrospectively reviewed. Patients' outcomes were evaluated 3 days, 1 month and 6 months after biopsy. Of the 49 biopsy cases, 41 were treated by transurethral prostatectomy, two by ureteroscopic lithotripsy, two by laparoscopic renal cyst decortication, two by cystostomy and two by ureteral stent extraction. The overall detection rate of clinically significant prostate cancer was 22.4%. The rate in patients with a prostate imaging reporting and data system (PI-RADS) score of 4-5 was 100%, while in cases with a PI-RADS score of <3 it was 7.1%. Postoperative complications within 3 days included hematuria in 39 (79.6%) cases, fever in three (6.1%) cases and hematochezia in two (4.1%) cases. There was no significant difference in the incidence of hematuria between the transrectal and transperineal approaches; however, the overall incidence of complications was significantly reduced after switching from a transrectal approach to a transperineal approach. No complications were observed after 1 or 6 months. In summary, combining simultaneous prostate biopsy to general urological surgeries is a safe and feasible approach. The transperineal approach has a lower incidence of complications. This method may benefit certain patients who are concurrently undergoing general urological surgeries and are under suspicion of prostate cancer in real-world clinical practice.

Pathological characteristics and predictive factors of prostate biopsy in patients with serum PSA levels between 0 and 4.0 ng/ml.

Background: This study aimed to analyze the pathological characteristics and predictive factors of prostate biopsy in men with PSA levels below 4.0 ng/ml. Patients and methods: We retrospectively analyzed 158 patients who underwent prostate biopsy with PSA levels below 4.0 ng/ml. Pathological results were statistically analyzed. The logistic regression analysis was used to determine the predictive factors for malignant outcomes. Subgroup analysis was performed on patients who received surgery and the postoperative pathological upgrading was counted. Results: A total of 143 patients were enrolled. The tumor detection rate was 20.3%. Among these patients, most of them (79.3%) had prostate adenocarcinoma, but rare malignant tumors also accounted for 20.7%. Logistic regression analysis indicated that the only independent predictive factor for a positive prostate biopsy was the PI-RADS score. For prostate adenocarcinoma cases, 95.7% of them were organ localized and 47.8% of cases were clinically significant. Subgroup analysis was performed on 14 patients who received surgical treatment. 28.6% of patients were upgraded to clinically significant prostate cancer, while 64.3% of patients had an upgrade in tumor stage. Conclusion: Our study indicated that 20.3% of men with PSA levels between 0 and 4.0 ng/ml were diagnosed with prostate malignancies. Among these patients, most of them (79.3%) were diagnosed with prostate adenocarcinoma, and several uncommon types of malignancies were also detected in 20.7% of patients. The only risk factor for a positive biopsy in patients with a low PSA concentration was the PI-RADS score. It should be emphasized that the invasiveness of PCa patients diagnosed by biopsy may be underestimated as more than half of patients will upgrade their Gleason score or clinical stages after surgery. Thus, clinicians should pay more attention to patients with PSA levels between 0 and 4.0 ng/ml.

The application of 3D bioprinting in urological diseases.

Urologic diseases are commonly diagnosed health problems affecting people around the world. More than 26 million people suffer from urologic diseases and the annual expenditure was more than 11 billion US dollars. The urologic cancers, like bladder cancer, prostate cancer and kidney cancer are always the leading causes of death worldwide, which account for approximately 22% and 10% of the new cancer cases and death, respectively. Organ transplantation is one of the major clinical treatments for urological diseases like end-stage renal disease and urethral stricture, albeit strongly limited by the availability of matching donor organs. Tissue engineering has been recognized as a highly promising strategy to solve the problems of organ donor shortage by the fabrication of artificial organs/tissue. This includes the prospective technology of three-dimensional (3D) bioprinting, which has been adapted to various cell types and biomaterials to replicate the heterogeneity of urological organs for the investigation of organ transplantation and disease progression. This review discusses various types of 3D bioprinting methodologies and commonly used biomaterials for urological diseases. The literature shows that advances in this field toward the development of functional urological organs or disease models have progressively increased. Although numerous challenges still need to be tackled, like the technical difficulties of replicating the heterogeneity of urologic organs and the limited biomaterial choices to recapitulate the complicated extracellular matrix components, it has been proved by numerous studies that 3D bioprinting has the potential to fabricate functional urological organs for clinical transplantation and in vitro disease models.

Process Optimization of Electrochemical Treatment of COD and Total Nitrogen Containing Wastewater.

In this work, an electrochemical method for chemical oxygen demand (COD) and total nitrogen (TN, including ammonia, nitrate, and nitrite) removal from wastewater using a divided electrolysis cell was developed, and its process optimization was investigated. This process could effectively relieve the common issue of NO3-/NO2- over-reduction or NH4+ over-oxidation by combining cathodic NO3-/NO2- reduction with anodic COD/NH4+ oxidation. The activity and selectivity performances toward pollutant removal of the electrode materials were investigated by electrochemical measurements and constant potential electrolysis, suggesting that Ti electrode exhibited the best NO3-/NO2- reduction and N2 production efficiencies. In-situ Fourier transform infrared spectroscopy was used to study the in-situ electrochemical information of pollutants conversion on electrode surfaces and propose their reaction pathways. The effects of main operating parameters (i.e., initial pH value, Cl- concentration, and current density) on the removal efficiencies of COD and TN were studied. Under optimal conditions, COD and TN removal efficiencies from simulated wastewater reached 92.7% and 82.0%, respectively. Additionally, reaction kinetics were investigated to describe the COD and TN removal. Results indicated that COD removal followed pseudo-first-order model; meanwhile, TN removal followed zero-order kinetics with a presence of NH4+ and then followed pseudo-first-order kinetics when NH4+ was completely removed. For actual pharmaceutical wastewater treatment, 79.1% COD and 87.0% TN were removed after 120 min electrolysis; and no NH4+ or NO2- was detected.

Predictability and usefulness of intravascular ultrasound-guided angioplasty in patients with femoropopliteal lesions.

INTRODUCTION: The aim of this study was to assess whether intravascular ultrasound (IVUS)-guided angioplasty in femoropopliteal lesions would improve clinical outcomes and predict restenosis. EVIDENCE ACQUISITION: Studies in which IVUS-guided angioplasty was used for femoropopliteal lesions were searched from the MEDLINE, Embase, Web of Science, and Cochrane databases; articles with the full text were included. The primary endpoint of this study was primary patency at 12 months, while the secondary endpoints were primary patency at 24 months, freedom from target lesion revascularization (TLR) at 12 months, and correlation of restenosis with the distal external elastic membrane (EEM) area, postintervention minimum lumen area, lesion length, dissection, and calcification. EVIDENCE SYNTHESIS: Altogether, 11 observational studies involving 1521 patients (1703 lesions) were analyzed. The quality of the evidence for 7 main outcomes was assessed as "very low" by The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) classification. The mean follow-up period was 1.5 years. The pooled rates were: 78% for 12-month primary patency (95% confidence interval [CI], 0.72-0.83), 74.3% for 24-month primary patency (95% CI: 0.71-0.78), and 80% for 12-month freedom from TLR (95% CI: 0.74-0.86). The 12-month primary patency of IVUS use (relative risk [RR], 2.01; 95% CI: 1.48-2.74) was higher compared to non-IVUS use. The minimum lumen (stent) area (standard mean difference [SMD] = -0.30; 95% CI: -0.46 to -0.15) and dissection (OR 1.58; 95% CI: 1.01-2.49, P=0.047), were associated with midterm patency in terms of restenosis. CONCLUSIONS: In IVUS-guided angioplasty in patients with femoropopliteal lesions, the minimum lumen (stent) area and dissection were associated with restenosis. Nevertheless, there is limited and heterogeneous evidence regarding the usefulness and Predictability of IVUS in patients with peripheral arterial disease in the femoropopliteal artery, especially in long-term patency and as a predictor of declining patency. The optimal role of IVUS in such patients should be elucidated in the future.

Bilateral hematoma after tubeless percutaneous nephrolithotomy for unilateral horseshoe kidney stones: A case report.

BACKGROUND: Bilateral perirenal hematoma is rarely reported in endoscopic management of horseshoe kidney stones, and there are few studies reporting the formation of bilateral hematoma following tubeless percutaneous nephrolithotomy (PCNL) for unilateral horseshoe kidney calculi. CASE SUMMARY: A 32-year-old man was admitted to our hospital because of repeated intermittent hematuria for 10 years. Plain abdominal computed tomography (CT) scan revealed calculi in the horseshoe kidney; the largest being 2 cm in diameter. Tubeless PCNL was performed to remove the stones. Three days after the operation, the patient was discharged in a stable situation. Three days after discharge, the patient presented to our emergency department because of right low back pain and vomiting. Emergent CT scan revealed subcapsular and perirenal hematocele and exudates in both kidneys. Ultrasound-guided puncture and drainage of perirenal effusion were performed. After the temperature stabilized, the patient received low-pressure injection of urokinase 100000 U for 3 d. His routine blood indexes and the renal function returned to normal in 3 wk. CT re-examination 3 mo after lithotripsy showed that the subcapsular and perirenal hematoma and exudates in both kidneys were significantly absorbed as compared with those before. The patient was followed up for 1 year, during which no flank pain or hematuria recurred. CONCLUSION: This is the first case report on the formation of bilateral hematoma following tubeless PCNL for unilateral horseshoe kidney calculi.

Atypical granular cell tumor of the urinary bladder: A case report.

BACKGROUND: Granular cell tumor (GCT) is a neurogenic tumor mainly occurring in the head and neck. GCT in the genitourinary system is extremely rare and only sporadic cases of urinary bladder GCT have been reported. Most urinary bladder GCT cases are benign and only two malignant cases have been reported. Due to its rarity, no consensus criteria for the treatment of urinary bladder GCT are available at present. CASE SUMMARY: A 62-year-old Chinese woman was found to have a urinary bladder tumor without any clinical manifestations on physical examination. Cystoscopy revealed a semispherical shaped lesion measuring approximately 4.0 cm in diameter at the junction of the left wall and roof of the bladder, which was covered with normal bladder mucosa. Computed tomography scan demonstrated a high-density lesion on the left wall of the bladder, measuring approximately 2.9 cm × 2.4 cm with clear boundaries. Contrast-enhanced pelvic magnetic resonance imaging revealed a space-occupying lesion on the left wall of the bladder (non-mucosal origin/ external pressure), which was preliminarily suspected to be a desmoplastic fibroma or leiomyoma. In the context of the above findings, a pre-operative diagnosis of bladder leiomyoma was made. The patient consequently underwent a laparoscopic partial cystectomy. The resected bladder mass looked yellowish and well-demarcated, measuring 4.0 cm × 3.5 cm and infiltrated the muscular layer. The diagnosis of urinary bladder GCT was finally made by postoperative pathology, with positive immunohistochemical S-100 staining and negative pancytokeratin. The patient has been followed for 6 mo so far, with no tumor recurrence detected. CONCLUSION: This case highlights the biological feature and differential diagnosis of urinary bladder GCT at the pathological and molecular levels. Transurethral resection of the bladder tumor and partial cystectomy are recommended in most urinary bladder GCT cases, while radical cystectomy is recommended in malignant cases.

Modified Predictive Model and Nomogram by Incorporating Prebiopsy Biparametric Magnetic Resonance Imaging With Clinical Indicators for Prostate Biopsy Decision Making.

PURPOSE: The purpose of this study is to explore the value of combining bpMRI and clinical indicators in the diagnosis of clinically significant prostate cancer (csPCa), and developing a prediction model and Nomogram to guide clinical decision-making. METHODS: We retrospectively analyzed 530 patients who underwent prostate biopsy due to elevated serum prostate specific antigen (PSA) levels and/or suspicious digital rectal examination (DRE). Enrolled patients were randomly assigned to the training group (n = 371, 70%) and validation group (n = 159, 30%). All patients underwent prostate bpMRI examination, and T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences were collected before biopsy and were scored, which were respectively named T2WI score and DWI score according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v.2) scoring protocol, and then PI-RADS scoring was performed. We defined a new bpMRI-based parameter named Total score (Total score = T2WI score + DWI score). PI-RADS score and Total score were separately included in the multivariate analysis of the training group to determine independent predictors for csPCa and establish prediction models. Then, prediction models and clinical indicators were compared by analyzing the area under the curve (AUC) and decision curves. A Nomogram for predicting csPCa was established using data from the training group. RESULTS: In the training group, 160 (43.1%) patients had prostate cancer (PCa), including 128 (34.5%) with csPCa. Multivariate regression analysis showed that the PI-RADS score, Total score, f/tPSA, and PSA density (PSAD) were independent predictors of csPCa. The prediction model that was defined by Total score, f/tPSA, and PSAD had the highest discriminatory power of csPCa (AUC = 0.931), and the diagnostic sensitivity and specificity were 85.1% and 87.5%, respectively. Decision curve analysis (DCA) showed that the prediction model achieved an optimal overall net benefit in both the training group and the validation group. In addition, the Nomogram predicted csPCa revealed good estimation when compared with clinical indicators. CONCLUSION: The prediction model and Nomogram based on bpMRI and clinical indicators exhibit a satisfactory predictive value and improved risk stratification for csPCa, which could be used for clinical biopsy decision-making.

Identification of novel biomarkers in Hunner's interstitial cystitis using the CIBERSORT, an algorithm based on machine learning.

BACKGROUND:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC. METHODS: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560. RESULTS: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560. CONCLUSION: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers.