Search

Genetic variation in UDP-glucuronosyltransferase 1A1 gene (UGT1A1) is a lithogenic risk factor for gallstone formation. This study aimed to assess genotype and allele frequencies of common UGT1A1 variants in patients with gallstone and hepatitis B virus (HBV)-related hepatic failure. This study enrolled 113 healthy individuals (CTRL), 54 patients with HBV infection (HBV), 134 patients with gallstone-free hepatic failure and HBV infection, and 34 patients with gallstone-related hepatic failure and HBV infection (GRHF). Peripheral venous blood samples were collected for genomic DNA isolation. Polymerase chain reaction amplification was carried out for UGT1A1, followed by direct sequencing. Analysis for genotype and allele frequencies of UGT1A1 variants (UGT1A1*6, UGT1A1*27, UGT1A1*28, and UGT1A1*60) was performed. The allele distributions of the four groups did not deviate from Hardy–Weinberg equilibrium. Allele (A) and genotype (CA) frequency distributions of UGT1A1*27 were significantly different between GRHF and CTRL, or between GRHF and HBV. GRHF and CTRL exhibited significant differences in allele (A) and genotype (CA) frequency distributions of UGT1A1*28. Linkage disequilibrium analysis suggested that haplotype G-G-[TA]7-T may be associated with gallstone in HBV-related hepatic failure. Our data reveal that UGT1A1*27 and UGT1A1*28 variants are significantly observed in patients with GRHF compared to healthy individuals.

Objectives: Performing immediate radical cystectomy in all patients with the highest‐risk non‐muscle invasive bladder cancer results in overtreatment. We confirm whether the substratification of highest‐risk patients can more effectively select suitable patients for radical cystectomy. Methods: Patients with primary T1 high grade bladder cancer from two centers were included and roughly stratified into high‐risk or highest‐risk. The highest‐risk patients were further substratified according to the number of risk factors. Endpoints were tumor recurrence and progression. The predictive accuracy was assessed with internal validation that consists of time‐dependent receiver operating characteristic curve and calibration curves. Results: A total of 262 patients were included. Although highest‐risk patient had a poor prognosis, after further substratification, we found that those with only one factor showed the same prognosis with high‐risk patients (recurrence: hazard ratio 1.79, P = 0.105; progression: hazard ratio 1.38, P = 0.532), while those with ≥2 factors had worst prognosis than high‐risk patients. The 3‐year area under the curve showed that the predictive accuracy of substratification in terms of recurrence and progression were superior to that of non‐substratification (0.685 vs 0.622 and 0.666 vs 0.599, respectively). Additionally, calibration curves showed perfect agreement between the predicted and the actual recurrence and progression. Conclusions: Substratification of highest‐risk enables us to further optimize the surgical decisions‐making. Highest‐risk patients with one factor show the similar outcomes as high‐risk patients and deserve to try bladder‐sparing treatment, whereas those with ≥2 risk factors were strongly recommended to undergo radical cystectomy. [ABSTRACT FROM AUTHOR]

Introduction: To get insight into the temporal trends of urolithiasis, and thus decrease the health burden of urolithiasis, we comprehensively investigated the specific epidemiological indicators that varied among different countries and regions according to the diversity of geographic locations, gender, age, year, and socioeconomic status. Methods: In this study, we investigated the incidence, death, disability-adjusted life years (DALYs) of urolithiasis quantified by the number of patients, age-standardized rates, and estimated annual percentage changes based on geographic locations, gender, age, and year to decode the epidemiological characteristics using the data from 1990 to 2019 in the Global Burden of Disease database. Results: In 2019, more than 115 million (95% uncertainty interval [95% UI] 93– 140) incident cases of urolithiasis occurred worldwide, and the age-standardized incidence rate (ASIR) (per 100,000 population) decreased from 1696.2 (1358.1– 2078.1) in 1990 to 1394 (1126.4– 1688.2) in 2019. Nearly 13,279 (95% UI: 10616– 16267) died of urolithiasis, contributing to 0.6 million (0.5– 0.7) DALYs in 2019. The highest age-standardized DALY rates (33.33 per 100 000 population) in 2019 were observed in Armenia, whereas the largest negative estimated annual percentage changes of DALYs were seen in Poland. The ASIR of males was higher than females. However, the ASIR EAPC of males was lower than females from 1990 to 2019. Males aged 50– 54 years old were more likely to suffer from urolithiasis. Joinpoint regression model analyses suggested that the global age-standardized incidence and DALY rates of urolithiasis encountered a trend to decline over the past 30 years. Over the years, the attenuation of this disease was pinpointed to be weakly related to the Socio-demographic index. Conclusion: At the global level, both the incident and DALY cases experienced substantial growth compared to the absolute cases in 1990. However, global age-standardized incidence and DALY rate of urolithiasis were observed to decline from 1990 to 2019. Males' ASIR was higher than females, while the gap narrowed over the years. A weakly positive correlation between ASIR of urolithiasis and SDI was also observed in this study. [ABSTRACT FROM AUTHOR]

3D bioprinting has been developed as an effective and powerful technique for the fabrication of living tissue constructs in a well-controlled manner. However, most existing 3D bioprinting strategies face substantial challenges in replicating delicate and intricate tissue-specific structural organizations using mechanically weak biomaterials such as hydrogels. Embedded bioprinting is an emerging bioprinting strategy that can directly fabricate complex structures derived from soft biomaterials within a supporting matrix, which shows great promise in printing large vascularized tissues and organs. Here, we provide a state-of-the-art review on the development of embedded bioprinting including extrusion-based and light-based processes to manufacture complex tissue constructs with biomimetic architectures. The working principles, bioinks, and supporting matrices of embedded printing processes are introduced. The effect of key processing parameters on the printing resolution, shape fidelity, and biological functions of the printed tissue constructs are discussed. Recent innovations in the processes and applications of embedded bioprinting are highlighted, such as light-based volumetric bioprinting and printing of functional vascularized organ constructs. Challenges and future perspectives with regard to translating embedded bioprinting into an effective strategy for the fabrication of functional biological constructs with biomimetic structural organizations are finally discussed. It is still challenging to replicate delicate and intricate tissue-specific structural organizations using mechanically-weak hydrogels for the fabrication of functional living tissue constructs. Embedded bioprinting is an emerging 3D printing strategy that enables to produce complex tissue structures directly inside a reservoir filled with supporting matrix, which largely widens the choice of bioprinting inks to ECM-like hydrogels. Here we aim to provide a comprehensive review on various embedded bioprinting techniques mainly including extrusion-based and light-based processes. Various bioinks, supporting matrices, key processing parameters as well as their effects on the structures and biological functions of resultant living tissue constructs are discussed. We expect that it can provide an important reference and generate new insights for the bioprinting of large vascularized tissues and organs with biological functions. [Display omitted] [ABSTRACT FROM AUTHOR]

Raman spectroscopy is an optical technique that can potentially serve as a molecular diagnosis method. This approach is excellent in many aspects for diagnosing bladder tumors, and over the last 20 years, there has been a rapid increase in the number of related studies. However, no review article has covered the wide use of Raman spectroscopy in bladder tumors. A total of 26 original studies have suggested that Raman spectroscopy shows good performance in diagnosing bladder tumors from 4 aspects, including tissue sections, endoscopic methods, cell screening, and biomarkers. However, Raman spectroscopy needs to be modified by combining it with other techniques, and studies based on a large population are still urgently needed to expand its clinical value. [ABSTRACT FROM AUTHOR]

Introduction: To assess the rate and location of residual tumor in re-transurethral resection of bladder tumor (re-TURBT) and develop a risk stratification tool to assist clinicians in making treatment decisions. Patients and Methods: The data of 144 patients with high-risk bladder cancer who received re-TURBT were retrospectively reviewed. The rate and location of residual tumors was recorded. Logistic regression was performed to explore risk factors for residual tumors, and a risk classification tool was developed. Results: Among the 144 patients, the rates of residual tumor and tumor location at the base of the primary tumor were 22.2% and 10.4%, respectively. Non-urothelial carcinoma subspecialist, piecemeal resection and the absence of detrusor muscle in the first specimen were defined as risk factors. Patients were categorized into low-, intermediate-, and high-risk groups according to the number of risk factors. The rate of residual tumor in the high-risk group was significantly higher than that in the low- and intermediate-risk groups (50% vs. 7.8%, P =0.001; 50% vs. 18.6%, P =0.002). Moreover, high-risk patients benefitted more from a second resection at the base of the primary tumor due to the high rate of residual tumor located at this site than low- and intermediate-risk patients (23.5% vs. 2.0%, P =0.002; 23.5% vs. 10.2%, P =0.083). Conclusions: Risk stratification based on the subspecialist category, operative method, and presence or absence of detrusor muscle in the first specimen could help identify patients who benefit from re-TURBT and second resection the base of the primary tumor. [ABSTRACT FROM AUTHOR]

The last decade has witnessed revolutionary advances taken in immunotherapy for various malignant tumors. However, immune-related molecules and their characteristics in the prediction of clinical outcomes and immunotherapy response in clear cell renal cell carcinoma (ccRCC) remain largely unclear. C-C Motif Chemokine Ligand 4 (CCL4) was extracted from the intersection analysis of common differentially expressed genes (DEGs) of four microarray datasets from the Gene Expression Omnibus database and immune-related gene lists in the ImmPort database using Cytoscape plug-ins and univariate Cox regression analysis. Subsequential analysis revealed that CCL4 was highly expressed in ccRCC patients, and positively correlated with multiple clinicopathological characteristics, such as grade, stage and metastasis, while negatively with overall survival (OS). We performed gene set enrichment analysis (GSEA) and gene set variant analysis (GSVA) with gene sets coexpressed with CCL4, and observed that gene sets positively related to CCL4 were enriched in tumor proliferation and immune-related pathways while metabolic activities in the negatively one. To further explore the correlation between CCL4 and immune-related biological process, the CIBERSORT algorithm, ESTIMATE method, and tumor mutational burden (TMB) score were employed to evaluate the tumor microenvironment (TME) characteristics of each sample and confirmed that high CCL4 expression might give rise to high immune cell infiltration. Moreover, correlation analysis revealed that CCL4 was positively correlated with common immune checkpoint genes, such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and lymphocyte activating 3 (LAG3). Overall, this study demonstrated that CCL4 might serve as a potential immune-related prognostic biomarker to predict clinical outcomes and immunotherapy response in ccRCC. Moreover, CCL4 might contribute to TME modulation, indicating the mechanism CCL4 involved in tumor proliferation and metastasis, which could provide novel therapeutic perceptions for ccRCC patients. [ABSTRACT FROM AUTHOR]

Clear cell renal cell carcinoma (ccRCC) is widely acknowledged to be extremely sensitive to immunotherapy, emphasizing the tremendous impacts on which the tumor microenvironment (TME) has shown. However, the molecular subgroups characterized by the TME features scarcely serve as the risk stratification guides in clinical practice for survival outcomes and immunotherapy response prediction. This study generated fresh insights into a novel TME-related prognostic signature derived from The Cancer Genome Atlas database using integrated bioinformatics analyses. Subsequently, Kaplan–Meier survival analysis, receiver operating characteristic analysis, and univariate and multivariate Cox regression analysis were performed to evaluate and validate the efficacy and the accuracy of the signature in ccRCC prognosis. Furthermore, we discovered that the risk score presented an increased likelihood of correlation with miscellaneous clinicopathological characteristics, natural killer cell-mediated cytotoxicity, immune cell infiltration levels, and immune checkpoint expression. These findings highlighted the notion that the six-gene signature characterized by the TME features may have implications on the risk stratification for personalized and precise immunotherapeutic management. [ABSTRACT FROM AUTHOR]

Objective: To compare the safety and outcomes between green‐light laser en bloc resection and transurethral resection of bladder tumor. Methods: A single‐center, randomized controlled trial was carried out from August 2014 to September 2018. Patients with initial non‐muscle‐invasive bladder cancer were randomized to green‐light laser en bloc resection or transurethral resection of bladder tumor. The primary outcomes were pathological findings and perioperative events. The secondary outcome was tumor recurrence. Results: A total of 233 patients were randomized to the transurethral resection of bladder tumor group (117 patients) and the green‐light laser en bloc resection group (116 patients). The resection time was longer in the green‐light laser en bloc resection group (P = 0.022); however, no differences were identified in overall operative time (P = 0.255). Nine patients (7.7%) had an obturator nerve reflex during transurethral resection of bladder tumor. The estimated volume of blood loss was significantly lower in the green‐light laser en bloc resection group (P = 0.012). The green‐light laser en bloc resection group had a higher rate of T1 bladder cancer (P = 0.031). A total of 104 patients (89.7%) treated with green‐light laser en bloc resection had detrusor muscle presence in the specimen, whereas 37 (31.9%) patients had the presence of muscularis mucosae, which was significantly higher than the corresponding number of transurethral resection of bladder tumor patients (P = 0.005 and 0.002, respectively). After a median follow‐up period of 48 months, just five patients had tumor recurrence (three in the transurethral resection of bladder tumor group and two in the green‐light laser en bloc resection group), and there was no difference between these two groups. Conclusions: Compared with transurethral resection of bladder tumor, green‐light laser en bloc resection is more effective due to less obturator nerve reflex and the same recurrence rate. Most importantly, green‐light laser en bloc resection can provide better tumor specimens for pathological examinations. [ABSTRACT FROM AUTHOR]

Introduction: The efficiency of the T1 sub-staging system on categorizing bladder cancer (BC) patients into subgroups with different clinical outcomes was unclear. We summarized relevant evidences, including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS), to analyze the prognostic significance of T1 sub-stage. Methods: Systematic literature searches of MEDLINE, EMBASE, and the Cochrane Library were performed. We pooled data on recurrence, progression, and CSS from 35 studies. Results: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated the difference in RFS between T1a sub-stage and T1b sub-stage (HR 1.28, 95% CI 1.14–1.43, p < 0.001). The significant difference was observed in PFS between the 2 arms (HR 2.18, 95% CI 1.95–2.44, p < 0.001). Worse CSS was found in T1b patients than in T1a patients (HR 1.36, 95% CI 1.21–1.54, p < 0.001). Conclusions: T1 sub-staging system based on the invasion depth into muscularis mucosae can be a significant prognostic factor for RFS, PFS, and CSS of patients with T1 BC. Urologists and pathologists are encouraged to work together to give a precise sub-stage classification of T1 BC, and T1 sub-staging system should be a routine part of any histopathological report when possible. Different treatment strategies need to be developed for both T1a BC and T1b BC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the feasibility and initial surgical outcomes of transurethral enucleation for 6 patients with bladder leiomyoma. Materials: Six patients (mean age 50.2, range [34–67]) with bladder leiomyoma underwent transurethral enucleation. In each case, the resectoscope was inserted into the bladder. A resecting loop was used to incise the urothelium along the surgical margin of the bladder tumor, and a push was given through the resecting loop to further separate the tumor until it was shelled off the bladder wall. The intact mass was then cut into pieces and flushed out. After the operation, irrigation therapy was given. Results: Surgery was performed successfully in all 6 patients. The mean size of the tumor was 3.9 cm (1.8–6.7 cm). The mean operation time was 60 min (30–100 min). The mean follow-up period was 14.8 months (2–30 months), and no evidence of recurrence was found in all cases. Conclusion: Transurethral enucleation is a safe, reliable, and effective surgical technique for selected patients with well-encapsulated tumors and is well suited for further pathological diagnosis and radical treatment. [ABSTRACT FROM AUTHOR]

Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial‑to‑mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24‑parental (P) and T24‑lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24‑P cells, mesenchymal‑like T24‑L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia‑inducible factor (HIF)‑1α, zinc finger E‑box‑binding homeobox 1 (ZEB1), vimentin and N‑cadherin and lower level of cytokeratin 18 were observed. Mechanistically, it was identified that HIF‑1α increases ZEB1 expression and subsequently regulates the expression of EMT‑related genes in both HIF‑1α knocking down by siRNA and gain‑in HIF‑1α by hypoxia culture cell models. In addition, the expression of HIF‑1α and ZEB1 in bladder cancer tissues were increased compared with normal bladder epithelial tissues, as well as significantly increased in the high‑grade, invasive and metastatic bladder cancer tissues compared with low‑grade, superficial and non‑metastatic bladder cancer tissues by using immune‑histochemical staining assay. Notably, the protein level of HIF‑1α was positively associated with that of ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF‑1α promotes ZEB1 expression and EMT in the T24‑L human bladder cancer lung metastasis animal model, suggesting that HIF‑1α serves an important function in the metastasis of bladder cancer, and HIF‑1α and ZEB1 may be potential targets for inhibiting bladder metastasis in the future. [ABSTRACT FROM AUTHOR]