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AIMS: To fabricate a novel nanoyarn biomaterial via a dynamic liquid electrospinning system, and to simultaneously evaluate whether nanoyarn is capable of being applied as a urinary sling for future clinical transfer. METHODS: Nanoyarn was cultured with adipose-derived stem cells (ADSCs). Cell morphology and function were observed on nanoyarn. Female rats that underwent vagina dilatation (VD) and bilateral ovarian resection (BOR) were used as the urinary incontinence model. After 2 weeks, the cells-sling was fixed to the suburethra. A commercial sling that tension-free vaginal tape-obturator (TVT-O) was used as a control. The urodynamic test for leak point pressure (LPP) and histological tests were used to evaluate the sling's performance in vivo. RESULTS: The nanoyarn possessed beneficial properties and the actin filament from ADSCs, which is very similar to muscle. Rats that underwent VD and BOR maintained a low LPP, whereas the LPP in rats with VD alone recovered to normal levels within 2 weeks. LPP in the nanoyarn group gradually decreased on the three urodynamic tests post-suburethral surgery, however, the cell-laden nanoyarn maintained LPP at normal levels for 8 weeks; the TVT-O group showed a significant increase in LPP at 8 weeks. Cell-laden nanoyarn was infiltrated with more cells, collagen, and vessels than the controls. CONCLUSIONS: The nanoyarn showed sufficient efficacy to maintain LPP in urinary incontinence rat model. In addition, it improved cell infiltration, collagen and muscle development compared to TVT-O. Thus, the combination of ADSCs and a nanoyarn scaffold could be a promising tissue-engineered sling for the treatment of urinary incontinence.
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Ingeniería de Tejidos , Andamios del Tejido , Incontinencia Urinaria de Esfuerzo/cirugía , Animales , Materiales Biocompatibles , Caproatos/química , Colágeno/química , Dioxanos/química , Femenino , Lactonas/química , Ratas , Cabestrillo SuburetralRESUMEN
PURPOSE: We determined whether endoscopic realignment or cystostomy would provide the best immediate management of pelvic fracture urethral injury. MATERIALS AND METHODS: We retrospectively reviewed the records of 590 patients with pelvic fracture urethral injury. Of the patients 522 were included in analysis due to strict criteria, including 129 in the endoscopic realignment group and 393 in the cystostomy group. Data on stricture formation and length, intervention technique and long-term functional outcomes were analyzed. RESULTS: In the endoscopic realignment group stricture developed in 111 patients (83%) at a mean of 23.5 months, which is longer than the 7.6 months reported in the cystostomy group (p <0.05). Mean stricture length was 3.2 cm in the realignment group and 3.7 cm in the cystostomy group (p <0.05). Internal urethrotomy was performed in 21 patients (19%) treated with realignment vs 18 (5%) treated with cystostomy (p <0.05). Further repair was accomplished via simple perineal anastomosis in 57 patients (51%) with realignment and 138 (35%) with cystostomy (p <0.05). Ancillary procedures such as corporeal splitting, inferior pubectomy and crural rerouting were necessary in 14 (13%), 14 (13%) and 5 patients (4%) in the endoscopic realignment group, and in 94 (24%), 100 (25%) and 43 (11%), respectively, in the cystostomy group (all p <0.05). The rates of impotence and incontinence did not statistically differ between the endoscopy and cystostomy groups (14.3% vs 16.2% and 1.6% vs 2.1%, respectively, p >0.05). CONCLUSIONS: Endoscopic realignment may reduce stricture formation and length, and facilitate urethroplasty. However, endoscopic realignment is also associated with a prolonged clinical course for recurrence.
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Fracturas Óseas/complicaciones , Complicaciones Posoperatorias/epidemiología , Uretra/lesiones , Enfermedades Uretrales/cirugía , Procedimientos Quirúrgicos Urológicos Masculinos/efectos adversos , Adolescente , Adulto , Anciano , Niño , Cistostomía/efectos adversos , Cistostomía/métodos , Endoscopía/efectos adversos , Endoscopía/métodos , Disfunción Eréctil/epidemiología , Disfunción Eréctil/etiología , Humanos , Masculino , Persona de Mediana Edad , Huesos Pélvicos/lesiones , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/efectos adversos , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Uretra/cirugía , Enfermedades Uretrales/etiología , Obstrucción Uretral/epidemiología , Obstrucción Uretral/etiología , Incontinencia Urinaria/epidemiología , Incontinencia Urinaria/etiología , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Adulto JovenRESUMEN
Currently there is little effective treatment available for castration resistant prostate cancer, which is responsible for the majority of prostate cancer related deaths. Emerging evidence suggested that cancer stem cells might play an important role in resistance to traditional cancer therapies, and the studies of cancer stem cells (including specific isolation and targeting on those cells) might benefit the discovery of novel treatment of prostate cancer, especially castration resistant disease. In this review, we summarized major biomarkers for prostate cancer stem cells, as well as their functional mechanisms and potential application in clinical diagnosis and treatment of patients.
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Biomarcadores/metabolismo , Células Madre Neoplásicas/patología , Neoplasias de la Próstata/terapia , Animales , Humanos , Masculino , Células Madre Neoplásicas/metabolismo , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/metabolismoRESUMEN
PURPOSE: To assess the efficacy of intra-arterial chemotherapy as a bladder-preservation treatment in patients with muscle-invasive bladder cancer (MIBC) following transurethral resection of bladder tumors (TURBT). MATERIALS AND METHODS: From 2005 June to 2012 November, 46 patients diagnosed with MIBC (clinical stage T2-T3N0M0) underwent three courses of cisplatin-based intra-arterial chemotherapy as a remedial approach for bladder preservation after TURBT. All patients also received intravesical instillation of chemotherapy as a maintenance strategy. RESULTS: All 46 patients completed the treatment with minor complications. The median follow-up time was 34.5 months (range, 8-87 months). Thirty-two patients (69.6%) demonstrated complete response. The three-year and five-year overall survival was 70.65 and 61.23%, and the disease-specific survival over the same periods was 78.03 and 67.62%, respectively. During the entire follow-up period, more than 80% preserved their bladder. CONCLUSIONS: Intra-arterial chemotherapy can be performed as a remedial treatment for MIBC patient following TURBT. Combined with TURBT, it offers an option for bladder preservation therapy on patients who are unable or unwilling to undergo radical cystectomy.
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Antineoplásicos/administración & dosificación , Cisplatino/administración & dosificación , Cistectomía/métodos , Tratamientos Conservadores del Órgano/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Administración Intravesical , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Quimioterapia Adyuvante , Cisplatino/efectos adversos , Cistectomía/efectos adversos , Cistectomía/mortalidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales , Estimación de Kaplan-Meier , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Tratamientos Conservadores del Órgano/efectos adversos , Tratamientos Conservadores del Órgano/mortalidad , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
OBJECTIVE: To report our 10-year diagnosis and treatment experience of acute urogenital and genitalia tract traumas and outline the management of the traumatic injury. METHODS: We reviewed the diagnoses and treatments of 208 cases of acute kidney, ureter, bladder, urethra, or male genitalia injuries in our department between March 2002 and March 2012. The patient data including general information, injury position and mechanism, diagnosis and treatment, the follow-up information was analyzed and summarized. RESULTS: Of 62 patients with renal injury examined by ultrasound and computed tomography (CT) examination, 45 were treated conservatively, 9 with superselective arterial embolization, and 8 with nephrectomy. Intravenous pyelogram (IVP) was conducted in two patients with ureteral injury, one was treated with cystoscopic ureteral catheterization and the other with ureteric reimplantation. Bladder injury (6 patients) confirmed with a waterflood susceptibility test combined with CT scans underwent laparotomy and the bladder suturing was done. Of 92 patients with urethral injury, 6 were treated with a nonoperative approach (indwelling catheter), 18 with urethral realignment, 35 with cystoscopic urethral realignment, 29 with end-to-end anastomotic urethroplasty, and 4 with urethral repairmen. Of the 24 cases with penile injuries, 1 underwent conservative treatment, 8 were treated with debridement and suture ligation, and 15 were managed with suture repair of the penis white membrane. Of the 24 cases with penile injuries, 1 underwent conservative treatment, 8 were treated with debridement and suture ligation, and 15 were managed with suture repair of the penis white membrane. During the follow-up period, 62 patients with renal injury had normal renal function. Neither of the two patients with ureteral injury developed hydronephrosis. Twenty-nine patients with urethral injury suffered from urethral structure. All patients with vesical or genital injury recovered. CONCLUSIONS: Urethra and kidney injuries are the most common acute urogenital system traumas. Superselective arterial embolization can effectively cease bleeding and maximally protect renal function and ureterorenoscopic realignment is an easily operative and minimally invasive technique in the treatment of urethral injuries. As diagnosis and treatment techniques continue to evolve, minimally invasive procedures should be widely used in acute urogenital trauma.
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BACKGROUND: With the rapid development of laparoscopic and robot-assisted surgery, many technological innovations and improvements have emerged to optimize minimally invasive surgery and ensure minimal patient risk. Although AirSeal has been widely reported in the field of urology, its perioperative outcomes and safety in minimally invasive urological surgery remain unclear because of inconsistent levels of evidence. OBJECTIVES: We performed this meta-analysis to evaluate the perioperative outcomes and safety of the valveless insufflation system(VIS) in minimally invasive urological surgery compared with the conventional insufflation system(CIS). METHODS: We comprehensively searched PubMed, Web of Science, Cochrane Library, and Embase databases to identify eligible studies published up to January 2024. Review Manager software (version 5.3.0) was used for the statistical analysis. Eligible studies were randomized controlled trials (RCTs) or non-RCTs of minimally invasive urological surgery with VIS vs CIS. The study outcomes included perioperative outcomes and safety. We excluded publication types, including letters, reviews, case reports, and animal and pediatric studies. RESULTS: We finally identified five RCTs and eight non-RCTs in this meta-analysis. The meta- analysis indicated that the operative time was comparable between the groups (P=0.57, I2=91%). However, a valveless insufflation system may increase blood loss (P=0.0004, I2=45%) and shorten hospital stays (P<0.00001, I2=90%). Due to the high heterogeneity of the results, we carefully evaluated all included studies and discovered that the studies by Bucur and Ferroni may be the sources of heterogeneity.When these two studies were excluded, heterogeneity was significantly reduced, and the operative time for VIS was significantly shorter than that for CIS (P=0.0002). Adjusted blood loss showed no difference between the VIS and CIS groups (P=0.10). In terms of safety, the pooled results revealed that the incidence of Clavien- Dindo III-IV complications in the VIS group was significantly lower than that in the CIS group (P=0.02, I2=0%). Moreover, VIS significantly reduced general pain (P=0.02, I2=15%) and shoulder pain (P=0.001, I2=0%) 12-24 hours postoperatively. No significant differences were observed in total complications (P=0.06, I2=0%), blood transfusion (P=0.14, I2=0%), and subcutaneous emphysema (P=0.96, I2=63%) between the two groups. CONCLUSIONS: Our meta-analysis revealed additional perioperative advantages of the valveless insufflation system in minimally invasive urological surgery. Moreover, VIS is superior to CIS owing to less severe complication rates, general pain, and shoulder pain.
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INTRODUCTION: Pelvic lymph node dissection (PLND) is commonly performed during radical prostatectomy (RP) for prostate cancer staging. This study aimed to comprehensively analyze existing evidence compare perioperative complications associated with standard (sPLND) versus extended PLND templates (ePLND) in RP patients. METHODS: A meta-analysis of prospective studies on PLND complications was conducted. Systematic searches were performed on Web of Science, Pubmed, Embase, and the Cochrane Library until May 2023. Risk ratios (RRs) were estimated using random-effects models in the meta-analysis. The statistical analysis of the data was carried out using Review Manager software. RESULTS: Nine studies, including three randomized clinical trial and six prospective studies, with a total of 4962 patients were analyzed. The meta-analysis revealed that patients undergoing ePLND had a higher risk of partial perioperative complications, such as lymphedema ( I2 =28%; RR 0.05; 95% CI: 0.01-0.27; P <0.001) and urinary retention ( I2 =0%; RR 0.30; 95% CI: 0.09-0.94; P =0.04) compared to those undergoing sPLND. However, there were no significant difference was observed in pelvic hematoma ( I2 =0%; RR 1.65; 95% CI: 0.44-6.17; P =0.46), thromboembolic ( I2 =57%; RR 0.91; 95% CI: 0.35-2.38; P =0.85), ureteral injury ( I2 =33%; RR 0.28; 95% CI: 0.05-1.52; P =0.14), intraoperative bowel injury ( I2 =0%; RR 0.87; 95% CI: 0.14-5.27; P =0.88), and lymphocele ( I2 =0%; RR 1.58; 95% CI: 0.54-4.60; P =0.40) between sPLND and ePLND. Additionally, no significant difference was observed in overall perioperative complications ( I2 =85%; RR 0.68; 95% CI: 0.40-1.16; P =0.16). Furthermore, ePLND did not significantly reduce biochemical recurrence ( I2 =68%; RR 0.59; 95% CI: 0.28-1.24; P =0.16) of prostate cancer. CONCLUSION: This analysis found no significant differences in overall perioperative complications or biochemical recurrence between sPLND and ePLND, but ePLND may offer enhanced diagnostic advantages by increasing the detection rate of lymph node metastasis.
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Pelvis , Neoplasias de la Próstata , Masculino , Humanos , Estudios Prospectivos , Pelvis/cirugía , Escisión del Ganglio Linfático/efectos adversos , Neoplasias de la Próstata/cirugía , Prostatectomía/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: Clear cell renal cell carcinoma (ccRCC), the most common type of RCC, typically produces no symptoms initially. Patients with ccRCC are at increased risk of developing advanced metastatic disease due to the absence of dependable and effective prognostic biomarkers. Therefore, it is particularly urgent to find optimal stratification of patients with ccRCC to distinguish the clinical benefits of different malignant degrees. Angiogenesis has a profound impact on the malignant behavior of renal cancer cells, and anti-angiogenic drugs have been applied to metastatic renal cancer patients. Moreover, immune function dysregulation is also a significant factor in tumorigenesis. We aim to construct a predictive model that combines angiogenesis and immune-related genes (AIRGs) to aid clinicians in predicting ccRCC prognosis. Methods: We gathered transcriptome and clinicopathology data from two datasets, the E-MTAB-1980 dataset and the Cancer Genome Atlas (TCGA). We utilized consensus clustering to find new molecular subgroups. A predictive model for the prognosis of angiogenesis-immune-associated genes (AIRGs) was conducted by the lasso and multivariate Cox regression analysis. The signature's predictive ability was then tested in different datasets. Meticulous scrutiny and comprehensive assessment were undertaken, both internally and externally, to establish the prognostic model. Analyses of immunogenomics were carried out to examine the relationship between risk scores and clinical/immune features, including immune cell infiltration, genomic alterations, and response to targeted and immunotherapy therapy. Results: Our prognostic signature, comprising 4 AIRGs, stood as an independent prognostic factor for ccRCC, while risk scores emerged as a novel indicator for forecasting overall survival. Risk scores exhibited significant associations with various immunophenotypic factors, such as oncogenic pathways, antitumor response, different immune cell infiltration, antitumor immunity, and response to targeted and immunotherapy therapy. Conclusions: AIRGs-based prognostic prediction model could effectively predict immunotherapy responses and survival outcomes of ccRCC.
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Adenoid cystic carcinoma (ACC), a rare malignancy, typically originates in salivary glands and is rarely found in other locations. In this case report, we describe a 54-year-old male patient who was presented to the Urology Department of Yantai Yuhuangding hospital with right-sided waist pain. The patient underwent percutaneous ultrasound-guided biopsies of lesions in the kidney and lung, which were histologically confirmed as primary adenoid cystic carcinoma of the lung and metastatic renal adenoid cystic carcinoma, respectively. Given the presence of multiple metastases, the patient received systemic palliative chemotherapy, which was well-tolerated and effectively controlled the tumor. At the last follow-up, there was no evidence of tumor progression in the patient.
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Carcinoma Adenoide Quístico , Neoplasias Renales , Neoplasias Pulmonares , Masculino , Humanos , Persona de Mediana Edad , Carcinoma Adenoide Quístico/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Riñón , HospitalesRESUMEN
OBJECTIVE: We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral stent-related symptoms. METHODS: Until August 2023, we conducted a comprehensive literature search on PubMed, Embase, Web of Science, and Cochrane Library to identify randomized controlled trials evaluating the efficacy and complications of tolterodine and α-adrenergic receptor blockers in treating ureteral stent-related symptoms. Two reviewers independently screened studies and extracted data. The scores from various domains of the Ureteral Stent Symptom Questionnaire (USSQ) were summarized and compared, and statistical analysis was performed using RevMan 5.4.0 software. RESULTS: A total of 8 studies met the inclusion criteria for our analysis. These studies were conducted at different centers. All studies were randomized controlled trials, involving a total of 487 patients, with 244 patients receiving α-adrenergic receptor blockers and 243 patients receiving tolterodine. The results showed that tolterodine demonstrated significantly better improvement in body pain (MD, 1.56; 95% CI [0.46, 2.66]; p = 0.005) (MD, 0.46; 95% CI [0.12, 0.80]; p = 0.008) (MD, 3.21; 95% CI [1.89, 4.52]; p = 0.00001) among patients after ureteral stent placement compared to α-adrenergic receptor blockers at different time points. Additionally, at 4 weeks, tolterodine showed superior improvement in general health (MD, 0.15; 95% CI [0.03, 0.27]; p = 0.01) and urinary symptoms (MD, 1.62; 95% CI [0.59, 2.66]; p = 0.002) compared to α-adrenergic receptor blockers, while at 6 weeks, tolterodine showed better improvement in work performance (MD, -1.60; 95% CI [-2.73, -0.48]; p = 0.005) compared to α-adrenergic receptor blockers. Additionally, the incidence of dry mouth (RR, 4.21; 95% CI [1.38, 12.87]; p = 0.01) is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, there were no significant statistical differences between the two drugs in other outcomes. CONCLUSION: This meta-analysis suggests that tolterodine is superior to α-adrenergic receptor blockers in improving physical pain symptoms after ureteral stent placement, while α-adrenergic receptor blockers are more effective than tolterodine in enhancing work performance. Additionally, the incidence of dry mouth is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, higher-quality randomized controlled trials are needed to further investigate this issue.
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Antagonistas Adrenérgicos alfa , Stents , Tartrato de Tolterodina , Uréter , Tartrato de Tolterodina/uso terapéutico , Humanos , Stents/efectos adversos , Antagonistas Adrenérgicos alfa/uso terapéutico , Uréter/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: This study aims to explore the prognostic significance of Proline-rich γ-carboxyglutamic acid protein 2 (PRRG2) in Kidney Renal Clear Cell Carcinoma (KIRC), a prevalent and deadly cancer, and its association with immune cell infiltration, a key strategy in developing effective biomarkers. METHODS: The study meticulously elucidated the prognostic significance and potential role of PRRG2 in KIRC, correlating its expression with patient sex, age, metastasis, and pathological stage. Utilizing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the involvement of PRRG2 in immune response was investigated. The association between PRRG2 expression and immune cell infiltration was also scrutinized. Ultimately, cellular and tissue identity were confirmed via immunohistochemical staining and quantitative real-time PCR. RESULTS: The study elucidates a notable decrease in PRRG2 expression in KIRC patients, correlating with demographic factors, metastasis, and pathological staging, and portending an unfavorable prognosis. Bioinformatic analyses underscore PRRG2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression. CONCLUSION: PRRG2 may potentially impact prognosis in KIRC patients by regulating immune infiltration, thus rendering PRRG2 a promising candidate prognostic biomarker for KIRC-associated immune infiltration.
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Objective: Urolithiasis is a common urological diseases and affects the daily life of patients. Medical expulsive therapy has become acceptable for many parents. We conducted a meta-analysis to determine the efficacy and safety of tadalafil compared with tamsulosin for treating distal ureteral stones less than 10 mm in length. Methods: Related studies were identified via searches of the PubMed, Embase, and Cochrane Library databases. All the articles that described the use of tadalafil and tamsulosin for treating distal ureteral stones were collected. Results: A total of 14 studies were included in our meta-analysis. Our results revealed that tadalafil enhanced expulsion rate [odds ratio (OR) = 0.68, 95% confidence interval (CI): 0.47 to 0.98, p = 0.04]; reduced expulsion time [mean difference (MD) = 1.22, 95% CI (0.13, 2.30), p = 0.03]; lowered analgesia use [MD = 38.66, 95% CI (7.56, 69.77), p = 0.01] and hospital visits [MD = 0.14, 95% CI (0.06, 0.22), p = 0.0006]. According to our subgroup analysis, either tadalafil 5 mg or 10 mg did not promote expulsion rate and accelerate expulsion time compared with tamsulosin. But patients receiving 5 mg tadalafil decreased analgesia usage [MD = 101.04, 95% CI (67.56, 134.01), p < 0.00001]. Conclusion: Compared with tamsulosin, tadalafil demonstrates a higher expulsion rate and less expulsion time for patients with distal ureteral stones less than 10 mm with a favorable safety profile.
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Objective: We conducted a meta-analysis to assess the efficacy and safety of mirabegron (50 mg/day) and antimuscarinics in treating ureteral stent-related symptoms (SRSs). Methods: All randomized controlled trials (RCTs) were identified by searching PubMed, Embase, Web of Science, and Cochrane Library. The RevMan version 5.3.0 software was used for statistical analysis. Results: This meta-analysis included five RCTs involving 317 patients. A fixed effects model revealed that mirabegron was superior to antimuscarinics in treating urinary symptoms (MD -1.39, 95% CI -2.63 to -0.15, p = 0.03) and general health (MD -1.65, 95% CI -2.60 to -0.69, p = 0.0007) 1 week after treatment initiation. We observed no significant differences in body pain (MD 0.05, 95% CI -1.06 to 1.15, p = 0.94), work performance (MD -0.86, 95% CI -1.77 to 0.06, p = 0.07), and sexual matters (MD 0.03, 95% CI -0.77 to 0.83, p = 0.94). Two weeks after treatment initiation, the ureteral stent symptom questionnaire (USSQ) revealed no significant differences between the two groups. The mirabegron group demonstrated a significant improvement in the quality of life (QoL) (MD -0.18, 95% CI -0.34 to -0.01, p = 0.03), while the International Prostate Symptom Score did not reveal a significant difference between the two groups (MD -0.74, 95% CI -1.79 to 0.32, p = 0.17). Regarding safety, a pooled data analysis presented that the incidence of constipation was lower in the mirabegron group (OR 0.10, 95% CI 0.01 to 0.77, p = 0.03). The mirabegron and antimuscarinics groups did not differ significantly concerning the risk of dry mouth (OR 0.15, 95% CI 0.02 to 1.27, p = 0.08). Conclusion: Mirabegron is superior to antimuscarinics in alleviating ureteral SRSs and improving QoL. Additionally, mirabegron 50 mg/day presented safety with a lower incidence of constipation.
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Cell-seeded scaffolds are a common route of cell transplantation for bladder repair and reconstruction. However, when cell suspensions are harvested, proteolytic enzymes often cause extracellular matrix damage and loss of intercellular junctions. To overcome this problem, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered adipose-derived stem cell (ASC) sheets, and evaluated its feasibility for bladder regeneration in a rat model. Adipose-derived stem cells (ASCs) were labeled with ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticles. ASC patches were constructed using multilayered USPIO-labeled ASC sheets and porous polyglycolic acid scaffolds. To monitor the distribution and localization of bioengineered bladder patches in live animals, magnetic resonance imaging (MRI) was performed 2â¯weeks, 4â¯weeks and 8â¯weeks after transplantation. The bladder regenerative potential of ASC patches was further evaluated by urodynamic and histological analysis. Scanning electron microscopy indicated that cell sheets adhered tightly to the scaffold. MRI showed hypointense signals that lasted up to 8â¯weeks at the site of USPIO-labeled ASC sheet transplants. Immunofluorescence demonstrated that these tissue-engineered bladder patches promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Urodynamic testing revealed that the ASC patch restored bladder function with augmented capacity. The USPIO-labeled ASC patch provides a promising perspective on image-guided tissue engineering and holds great promise as a safe and effective therapeutic strategy for bladder regeneration. STATEMENT OF SIGNIFICANCE: Adipose-derived stem cell (ASC) sheets avoid enzymatic dissociation and preserve the cell-to-cell interactions and extracellular matrix (ECM) proteins, which exhibit great potential for tissue regeneration. In this study, we developed a bioengineered three-dimensional bladder patch comprising porous scaffolds and multilayered ASC sheets, and evaluated its feasibility for bladder regeneration in a rat model. Tissue-engineered bladder patches restored bladder function and promoted regeneration of urothelium, smooth muscle, neural cells and blood vessels. Moreover, ultrasmall super-paramagnetic iron oxide (USPIO)-labeled bladder patches can be dynamically monitored in vivo by noninvasive MRI for long periods of time. Therefore, The USPIO-labeled bladder patch provides a promising image-guided therapeutic strategy for bladder regeneration.
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Tejido Adiposo/citología , Bioingeniería/métodos , Regeneración , Células Madre/citología , Vejiga Urinaria/fisiología , Animales , Apoptosis , Supervivencia Celular , Dextranos/ultraestructura , Femenino , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/ultraestructura , Ratas Sprague-Dawley , Coloración y Etiquetado , Células Madre/ultraestructura , Ingeniería de Tejidos , UrodinámicaRESUMEN
Several urinary tract pathologic conditions, such as strictures, cancer, and obliterations, require reconstructive plastic surgery. Reconstruction of the urinary tract is an intractable task for urologists due to insufficient autologous tissue. Limitations of autologous tissue application prompted urologists to investigate ideal substitutes. Tissue engineering is a new direction in these cases. Advances in tissue engineering over the last 2 decades may offer alternative approaches for the urinary tract reconstruction. The main components of tissue engineering include biomaterials and cells. Biomaterials can be used with or without cultured cells. This paper focuses on cell sources, biomaterials, and existing methods of tissue engineering for urinary tract reconstruction in China. The paper also details challenges and perspectives involved in urinary tract reconstruction.
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Ultrasonic degradation of six dextran samples with different initial molecular weights (IMW) has been performed to investigate the degradation behavior and chain scission mechanism of dextrans. The weight-average molecular weight (Mw) and polydispersity index (D value) were monitored by High Performance Gel Permeation Chromatography (HPGPC). Results showed that Mw and D value decreased with increasing ultrasonic time, resulting in a more homologous dextran solution with lower molecular weight. A significant degradation occurred in dextrans with higher IMW, particularly at the initial stage of the ultrasonic treatment. The Malhotra model was found to well describe the molecular weight kinetics for all dextran samples. Experimental data was fitted into two chain scission models to study dextran chain scission mechanism and the model performance was compared. Results indicated that the midpoint scission model agreed well with experimental results, with a linear regression factor of R2>0.99.
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Cell sheet therapy has emerged as a potential therapeutic option for reparation and reconstruction of damaged tissues and organs. However, an effective means to assess the fate and distribution of transplanted cell sheets in a serial and noninvasive manner is still lacking. To investigate the feasibility of tracking Adipose derived stem cells (ADSCs) sheet in vivo using ultrasmall super-paramagnetic Fe3O4 nanoparticles (USPIO), canine ADSCs were cultured and incubated with USPIO and 0.75 µg/ml Poly-L-Lysine (PLL) for 12 h. Labeling efficiency, cell viability, apoptotic cell rate were assessed to screen the optimum concentrations of USPIO for best labeling ADSCs. The results showed ADSCs were labeled by USPIO at an iron dose of 50 µg/ml for a 12 h incubation time, which can most efficiently mark cells and did not impair the cell survival, self-renewal, and proliferation capacity. USPIO-labeled ADSCs sheets can be easily and clearly detected in vivo and have persisted for at least 12 weeks. Our experiment confirmed USPIO was feasible for in vivo labeling of the ADSCs sheets with the optimal concentration of 50 µg Fe/ml and the tracing time is no less than 12 weeks.
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Óxido Ferrosoférrico/química , Imagen por Resonancia Magnética , Nanopartículas de Magnetita/química , Tejido Adiposo/citología , Animales , Apoptosis/efectos de los fármacos , Diferenciación Celular , Células Cultivadas , Perros , Nanopartículas de Magnetita/toxicidad , Ratones , Ratones Desnudos , Microscopía Electrónica de Transmisión , Osteogénesis , Piel/patología , Coloración y Etiquetado , Trasplante de Células Madre , Células Madre/química , Células Madre/citología , Células Madre/metabolismoRESUMEN
Urethral strictures remain a reconstructive challenge, due to less than satisfactory outcomes and high incidence of stricture recurrence. An "ideal" urethral reconstruction should establish similar architecture and function as the original urethral wall. We fabricated a novel tissue-engineered bionic urethras using cell sheet technology and report their viability in a canine model. Small amounts of oral and adipose tissues were harvested, and adipose-derived stem cells, oral mucosal epithelial cells, and oral mucosal fibroblasts were isolated and used to prepare cell sheets. The cell sheets were hierarchically tubularized to form 3-layer tissue-engineered urethras and labeled by ultrasmall super-paramagnetic iron oxide (USPIO). The constructed tissue-engineered urethras were transplanted subcutaneously for 3 weeks to promote the revascularization and biomechanical strength of the implant. Then, 2 cm length of the tubularized penile urethra was replaced by tissue-engineered bionic urethra. At 3 months of urethral replacement, USPIO-labeled tissue-engineered bionic urethra can be effectively detected by MRI at the transplant site. Histologically, the retrieved bionic urethras still displayed 3 layers, including an epithelial layer, a fibrous layer, and a myoblast layer. Three weeks after subcutaneous transplantation, immunofluorescence analysis showed the density of blood vessels in bionic urethra was significantly increased following the initial establishment of the constructs and was further up-regulated at 3 months after urethral replacement and was close to normal level in urethral tissue. Our study is the first to experimentally demonstrate 3-layer tissue-engineered urethras can be established using cell sheet technology and can promote the regeneration of structural and functional urethras similar to normal urethra.
Asunto(s)
Medios de Contraste/metabolismo , Dextranos/metabolismo , Técnicas de Cultivo de Órganos , Ingeniería de Tejidos/métodos , Uretra/fisiología , Animales , Biónica/métodos , Perros , Células Epiteliales/fisiología , Fibroblastos/fisiología , Técnica del Anticuerpo Fluorescente , Imagen por Resonancia Magnética , Nanopartículas de Magnetita , Coloración y Etiquetado/métodos , Células Madre/fisiología , Trasplantes/fisiologíaRESUMEN
Stromal cells in the peripheral zone (PZ) of the prostate from older males (PZ-old) could significantly promote Prostate cancer (PCa) growth compared with stromal cells from young males (PZ-young). But the mechanism is still unknown. In the co-culture system with PZ-old cells, Pc3/Du145 cells showed advanced proliferation and migration after Dihydrotestosterone (DHT) incubation, but DHT didn't show the similar effect in PZ-young co-culture system. Also, higher androgen/AR signal pathway activity and AR-related cytokines secretion (FGF-2, KGF, IGF-1) were found in PZ-old cells. As AR exprssison was equivalent in PZ-old and PZ-young cells, we focused on Androgen receptor associated protein-55(ARA55), a stromal-specific androgen receptor (AR) coactivator. ARA55 expression was higher in PZ-old cells compared with PZ-young cells in vitro. After knocking down ARA55 expression in PZ-old cells, the PCa growth- promoting effect from the PZ-old cells was diminished, which may be explained by the decreased the progressive cytokines secretion (FGF-2, KGF, IGF-1) from PZ-old stromal cells. In vivo, the consistent results were also found: PZ-old cells promoted prostate cancer cells growth, but this effect receded when knocking down ARA55 expression in PZ-old cells. From our study, we found PZ stromal cells presented age-related effects in proliferation and migration of prostate cancer cells in the androgen/AR dependent manner. As aging increased, more ARA55 were expressed in PZ stromal cells, leading to more sensitive androgen/androgen receptor (AR) signal pathway, then constituting a more feasible environment to cancer cells.
Asunto(s)
Envejecimiento/metabolismo , Andrógenos/metabolismo , Neoplasias de la Próstata/metabolismo , Células del Estroma/metabolismo , Adulto , Anciano , Envejecimiento/genética , Andrógenos/farmacología , Animales , Estudios de Casos y Controles , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Citocinas , Modelos Animales de Enfermedad , Expresión Génica , Xenoinjertos , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Unión Proteica , Receptores Androgénicos/metabolismo , Activación Transcripcional , Regulación hacia Arriba , Adulto JovenRESUMEN
The aim of this study was to evaluate the clinical outcomes achieved by use of preoperative intra-arterial chemotherapy and transurethral resection of bladder tumors as bladder preservation therapy in treatment of muscle-invasive bladder cancer. Patients with clinical stage T2-T4aN0M0 muscle-invasive bladder cancer were treated with 3 courses of preoperative cisplatin-based intra-arterial chemotherapy at 4-week intervals. Following treatment, the tumors were completely removed by transurethral resection, and all patients received epirubicin for intra-vesical instillation as a maintenance strategy. Patients showing a complete response received continuous monitoring, and radical cystectomy was strongly recommended for patients who did not achieve a complete response. Between August 2005 and October 2012, a total of 127 patients completed treatment with a bladder preservation therapy, and the median follow-up time for all patients was 31.9 months (range 5-87 months). Among these patients, 91 (71.7%) achieved a complete response, and the 5-year overall survival and disease-specific survival rates for all patients were 50.2 and 59.5%, respectively. Among the patients who demonstrated a complete response, 10 experienced a superficial relapse and 15 experienced an invasive cancer relapse. The 5-year recurrence-free and progression-free survival rates were 62.2 and 76.9%, respectively. An analysis of tumor-related factors suggested that clinical stage was significant for predicting both complete response and overall survival. These results suggest that preoperative intra-arterial chemotherapy combined with transurethral resection of the bladder tumor is useful for bladder preservation in certain patients with invasive bladder cancer. Patients with stage T2 tumors are best suited for this type of therapy.