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Background and purpose: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBT) is high. There are few studies on the risk factors of recurrence in NMIBC patients after initial TURBT. Our study aimed to screen the high-risk population and take corresponding preventive intervention measures by analyzing the risk factors of recurrence in NMIBC patients after initial TURBT. Methods: A total of 197 NMIBC patients who received initial TURBT in The Cancer Hospital of the University of Electronic Science and Technology of China from December 2015 to May 2020 were selected and followed up for 24 to 77 months. Patients were divided into recurrence group (48 cases) and non-recurrence group (149 cases) according to the results. Univariate analysis was performed on the clinical data of the two groups, and the indicators with statistical significance were included in the multivariate logistic regression analysis to screen the possible risk factors of recurrence. Results: Univariate analysis showed that the difference was statistically significant between two groups in gross hematuria, secondary resection, T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy (P 0.05). The receiver operating characteristic (ROC) curves of the ratio of neutrophils to lymphocytes and the ratio of neutrophils and hemoglobin to lymphocytes showed no statistically significant difference between two groups (P>0.05). Multivariate logistic regression analysis showed that T1 stage, high grade tumor, multiple tumor and lack of immediate intravesical therapy were independent risk factors of recurrence in NMIBC patients after initial TURBT (P 1). Conclusion: The recurrence of NMIBC patients after initial TURBT is closely related to tumor stage, tumor grade, tumor number and immediate intravesical therapy. Corresponding intervention measures can be taken to reduce the postoperative recurrence rate in initial NMIBC patients.

Background and purpose: Traditional preparation of subcutaneous transplanted tumor of prostate cancer relies on cell suspension injection. However, there are great limitations. The purpose of this study was to explore the feasibility of developing a new animal model of subcutaneous transplanted prostate cancer with cell sheet technology. Methods: Human prostate cancer DU145 cells were inoculated into a 35 mm temperature sensitive cell culture dish, and the prostate cancer cell sheet was prepared by continuous culture and identified by H-E staining and immunohistochemistry. According to the research purpose, cell suspension group and cell membrane group were set up. DU145 cell suspension was subcutaneously injected into nude mice in cell suspension group, and DU145 cell sheet was subcutaneously injected into BALB/c nude mice in cell sheet group. The BALB/c nude mice were sacrificed 4 weeks after transplantation, and the grafted tumors in both groups were dissected for further histological analysis, including collagen fiber content, local infiltration and angiogenesis. Meanwhile, the common organs of prostate cancer metastasis, such as bone, lung and liver, were dissected to evaluate the systemic metastasis in both groups. Results: DU145 prostate cancer cell sheet could be prepared at 1 week after continuous culture. Histological staining revealed a membrane structure with an average thickness of (32.6±7.5) μm. The DU145 cell sheet was rich in collagen fibrin with high vimentin expression and low E-cadherin expression. H-E staining showed that the tumor structure was dense with obvious infiltration of surrounding muscles in the cell sheet group, while the tumor had more vacuoles and a clear boundary with surrounding tissues in the cell suspension group 4 weeks after subcutaneous transplantation. Moreover, the transplanted tumor volume was significantly higher in the cell sheet group than in the cell suspension group, and the measured tumor volume in the two groups were (0.967±0.129) and (0.437±0.054) cm3 (t = 3.774, P = 0.019 5), respectively. Masson staining showed that the content of blue collagen fiber was significantly higher in the cell sheet group than in the cell suspension group, and the optical densities (D) value of the two groups were 0.023 0±0.001 1 and 0.014 0±0.000 7 (t = 7.022, P = 0.000 1), respectively. Immunohistochemical staining of CD31 showed that the microvascular density per ×200 field in the cell sheet group and the cell suspension group were 53.20±3.56 and 32.40±4.98 (t = 3.392, P = 0.009 5), respectively. Gross anatomy and H-E staining showed no obvious systemic metastasis in the two groups 4 weeks after subcutaneous transplantation. Conclusion: It is feasible and advantageous to develop the animal model of subcutaneous transplanted prostate cancer using cell sheet technology. Compared with traditional cell suspension injection method, the tumor volum was larger, the infiltration degree was deeper with surrounding tissues, the density of new microvessels was higher, and the collagen content was richer, which is more helpful to reveal the real biological characteristics of prostate cancer. It is expected to be applied in the research of molecular genetics of prostate cancer, drug resistance mechanism and drug discovery.

Background and purpose: 18 F-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography and computed tomography (PET/CT) is an advanced molecular imaging evaluation method for prostate cancer (PCa). This study aimed to explore the early detection rate of recurrence and metastasis of patients with biochemical recurrence (BCR) after radical prostatectomy (RP) by 18 F-PSMA-1007 PET/CT and its influence on clinical treatment decisions. Methods: From December 2018 to December 2020, the data of 51 PCa patients with BCR after RP by 18 F-PSMA-1007 PET/CT were summarized and analyzed. Radioactive uptake of tumors was calculated semi-quantitatively by region of interest method and expressed by the maximum standardized uptake value (SUV max ). We assessed the detection rate of clinical recurrence and metastasis in BCR patients [local recurrence (prostatic bed), lymph node metastasis (pelvic, retroperitoneal and diaphragmatic), bone metastasis and visceral metastasis (such as lung)], and the difference in detection rate between prostate-specific antigen (PSA) groups and Gleason evaluation group was further compared respectively. Results: The median age of 51 patients was 66 years (52-80 years), and the median PSA was 35 ng/mL (6-224 ng/mL) at the time of initial diagnosis. All of them were prostatic acinar adenocarcinoma, including 1 case with intraductal carcinoma, 1 case with ductal adenocarcinoma, 1 case with mucinous adenocarcinoma, 1 case with signet ring-like component and 1 case with neuroendocrine differentiation. We found Gleason score ≤7 in 22 cases (43.14%) and Gleason score ≥ 8 in 29 cases (56.86%). The median time of BCR was 15 months (5-62 months), and the median PSA was 0.58 ng/mL (0.20- 110.00 ng/mL), including 21 (41.18%) cases with 0.20 ng/mL≤PSA ＜ 0.50 ng/mL, 12 (23.53%) cases with 0.50 ng/mL≤PSA ＜ 1.00 ng/mL, 4 (7.84%) cases with 1.00 ng/mL≤PSA ＜ 2.00 ng/mL and 14 (27.45%) cases with PSA≥2.00 ng/mL. There were 7 cases (13.73%) with no local recurrence or metastasis, and 44 cases (86.27%) with local recurrence or metastasis, including 9 cases (20.45%) with recurrence in the operative area of prostate, 28 cases (63.64%) had lymph node metastasis at different sites, 31 cases (70.45%) had bone metastasis, and 2 cases (4.55%) had visceral metastasis. In addition, there were 2 cases of subcutaneous nodule metastasis and 1 case of penile root metastasis. The median SUV max was 17.9 (1.4-110.9) for all recurrence or metastasis, 14.0 (3.2-110.9) for local recurrence, 10.2 (2.0-90.1) for lymph node metastasis, and 5.4 (1.4-109.6) for bone metastasis. The detection rates of recurrence or metastasis were 71.43% (15/21), 100.00% (12/12), 75.00% (3/4) and 100.00% (14/14), respectively, in the groups with 0.20 ng/mL≤PSA ＜ 0.50 ng/mL (21 cases), 0.50 ng/mL≤PSA ＜ 1.00 ng/mL (12 cases), 1.00 ng/mL≤PSA ＜ 2.00 ng/mL (4 cases) and PSA≥2.00 ng/mL (14 cases), and there was no statistically significant difference in the detection rate between groups with different PSA levels (P＞0.05). The recurrence or metastasis detection rates of original Gleason score ≤7 group (22 cases) and Gleason score ≥8 group (29 cases) were 68.18% (15/22) and 100.00% (29/29), respectively, and there were statistically significant differences in the detection rate between groups with different Gleason scores (P ＜ 0.05). In clinical treatment, 4 cases (7.84%) were treated by observation, 18 cases (35.29%) by endocrinotherapy alone, 2 cases (3.92%) by salvage radiotherapy (SRT) alone, 24 cases (47.06%) by endocrinotherapy combined with SRT, 1 case (1.96%) by endocrinotherapy combined with docetaxel systemic chemotherapy, and 2 cases (3.92%) by salvage pelvic lymphadenectomy. Conclusion: 18 F-PSMA-1007 PET/CT has a good value and efficacy in early diagnosis of clinical recurrence or metastasis of BCR patients after RP, which is conducive to accurate evaluation and optimal treatment plan for such patients, and significantly affects clinical treatment decisions.

To date, the decellularized scaffold has been widely explored as a source of biological scaffolds for regenerative medicine. However, the acellular matrix derived from natural tissues and organs has a lot of defects, including the limited amount of autogenous tissue and surgical complication such as risk of blood loss, wound infection, pain, shock, and functional damage in the donor part of the body. In this study, we prepared acellular matrix using adipose-derived stem cell (ADSC) sheets and evaluate the cellular compatibility and immunoreactivity. The ADSC sheets were fabricated and subsequently decellularized using repeated freeze-thaw, Triton X-100 and SDS decellularization. Oral mucosal epithelial cells were seeded onto the decellularized ADSC sheets to evaluate the cell replantation ability, and silk fibroin was used as the control. Then, acellular matrix was transplanted onto subcutaneous tissue for 1 week or 3 weeks; H&E staining and immunohistochemical analysis of CD68 expression and quantitative real-time PCR (qPCR) were performed to evaluate the immunogenicity and biocompatibility. The ADSC sheet-derived ECM scaffolds preserved the three-dimensional architecture of ECM and retained the cytokines by Triton X-100 decellularization protocols. Compared with silk fibroin in vitro, the oral mucosal epithelial cells survived better on the decellularized ADSC sheets with an intact and consecutive epidermal cellular layer. Compared with porcine small intestinal submucosa (SIS) in vivo, the homogeneous decellularized ADSC sheets had less monocyte-macrophage infiltrating in vivo implantation. During 3 weeks after transplantation, the mRNA expression of cytokines, such as IL-4/IL-10, was obviously higher in decellularized ADSC sheets than that of porcine SIS. A Triton X-100 method can achieve effective cell removal, retain major ECM components, and preserve the ultrastructure of ADSC sheets. The decellularized ADSC sheets possess good recellularization capacity and excellent biocompatibility. This study demonstrated the potential suitability of utilizing acellular matrix from ADSC sheets for soft tissue regeneration and repair. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

microRNAs regulate subcellular functions through distinct molecular mechanisms. In this study, we used normal and pathogenic fibroblasts in pelvic fracture urethral distraction defects (PFUDD) patients. PFUDD is a common disease that could severely affect patients' life quality, yet little is known about the molecular mechanism associated with pathogenic fibrosis in PFUDD. Our data showed that let-7i-5p performs a multi-functional role in distinct signaling transduction pathways involved in cell morphology and cell migration in both normal and pathogenic fibroblasts. By analyzing the molecular mechanism associated with its functions, we found that let-7i-5p regulates through its direct target genes involved in collagen metabolism, cell proliferation and differentiation, TGF-beta signaling, DNA repair and ubiquitination, gene silencing and oxygen homeostasis. We conclude that let-7i-5p plays an essential role in regulating cell shape and tissue elasticity, cell migration, cell morphology and cytoskeleton, and could serve as a potential target for clinical treatment of urethral stricture patients., (Copyright © 2020 Zhang, Yang, Chen, Qi, Zhou, Wang, Fu, Chen and Fang.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

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.