Nano-sensitizer with self-amplified drug release and hypoxia normalization properties potentiates efficient chemoradiotherapy of pancreatic cancer.

The hypoxic nature of pancreatic cancer, one of the most lethal malignancies worldwide, significantly impedes the effectiveness of chemoradiotherapy. Although the development of oxygen carriers and hypoxic sensitizers has shown promise in overcoming tumor hypoxia. The heterogeneity of hypoxia-primarily caused by limited oxygen penetration-has posed challenges. In this study, we designed a hypoxia-responsive nano-sensitizer by co-loading tirapazamine (TPZ), KP372-1, and MK-2206 in a metronidazole-modified polymeric vesicle. This nano-sensitizer relies on efficient endogenous NAD(P)H quinone oxidoreductase 1-mediated redox cycling induced by KP372-1, continuously consuming periphery oxygen and achieving evenly distributed hypoxia. Consequently, the normalized tumor microenvironment facilitates the self-amplified release and activation of TPZ without requiring deep penetration. The activated TPZ and metronidazole further sensitize radiotherapy, significantly reducing the radiation dose needed for extensive cell damage. Additionally, the coloaded MK-2206 complements inhibition of therapeutic resistance caused by Akt activation, synergistically enhancing the hypoxic chemoradiotherapy. This successful hypoxia normalization strategy not only overcomes hypoxia resistance in pancreatic cancer but also provides a potential universal approach to sensitize hypoxic tumor chemoradiotherapy by reshaping the hypoxic distribution.

STING Membrane Prevents Post-Surgery Tissue Adhesion and Tumor Recurrence of Colorectal Cancer.

Surgery is the standard treatment regimen for resectable colorectal cancer (CRC). However, it is very hard to completely remove all cancer cells in clinical practice, leading to the high recurrence rates of the disease. Moreover, the post-surgery tissue adhesion greatly prevents the possibility of reoperation, significantly limiting the long-term surviving of CRC patients. To overcome CRC recurrence and avoid the post-surgery tissue adhesion, this work develops a novel stimulator of interferon genes "STING" membrane based on the coaxial electrospinning technology and hyaluronic acid modification. A reactive oxygen species responsive prodrug of gambogic acid (GB) and a potent STING agonist (CDN) are coloaded in the core-shell structure of the membrane, which endows the loaded drug with sustained and sequential release patterns. The localized delivery of GB and CDN can selectively induce efficient immunogenic cell death of cancer cells and then evoke the systemic anticancer immunity by activating the Cyclic GMP-AMP (cGAMP) synthase/STING pathway. As-designed "STING" membrane not only safely prevents tumor recurrence through the synergistic chemoimmunotherapy but also efficiently avoids the post-surgery tissue adhesion, facilitating the clinical intervention of CRC.

Baduanjin exercise intervention trial: research protocol of a randomised controlled trial for frail kidney transplant recipients.

INTRODUCTION: Frailty is one of the most common comorbidities in kidney transplant recipients (KTRs). Physical, psychological and social frailty could be improved by exercise intervention. Baduanjin, also known as Eight-section Brocades, is a type of traditional Chinese medicine exercise characterised by the interplay between physical postures and movements, breathing and mind. It can help frail patients strengthen their upper and lower body muscles, improve their mood, quality of life and frailty. However, the effectiveness of Baduanjin on frail KTRs remains unknown. Therefore, we will conduct a randomised controlled trial (RCT) to evaluate the effectiveness of Baduanjin on frail KTRs. METHODS AND ANALYSIS: This protocol describes an assessor and analyst blinded, parallel RCT for frail KTRs comparing Baduanjin group (n=72) with care-as-usual group (n=72). The primary outcomes are frailty assessed by Frailty Phenotype scale and Tilburg Frailty Indicator scale, and muscle strength assessed by a grip strength metre. The secondary outcomes are quality of life assessed by Medical Outcomes Study 36-Item Short-Form Health Survey (MOS SF-36) and depression assessed by the Hospital Anxiety and Depression Scale. All these data will be collected at the baseline, after 3, 6, 9 and 12 months, respectively. Two-way mixed analysis of variance (ANOVA) will be used to test the effectiveness of Baduanjin exercise. Qualitative interviews with participants in the intervention group will also be performed after 6 months. Themes will be extracted from interview transcripts using NVivo software. ETHICS AND DISSEMINATION: The Ethics Committees of Beijing University of Chinese Medicine (2022BZYLL1018) and China-Japan Friendship Hospital (2022-KY-250) had approved the study. The organ donors were all from China-Japan Friendship Hospital. They provided informed consent and they were not executed prisoners. We have provided BMJ Open with documentation from the hospital that indicates that the organs will be harvested ethically. The findings of this study will be disseminated through peer-reviewed journals, international conferences, media reports and briefings. TRIAL REGISTRATION NUMBER: ChiCTR2100041730.

Prognostic value of the systemic immune-inflammation index in patients with upper tract urothelial carcinoma after radical nephroureterectomy.

BACKGROUND: To investigate the prognostic significance of the systemic immune-inflammation index (SII) for patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) and develop nomogram models for predicting overall survival (OS), intravesical recurrence (IVR), and extra-urothelial recurrence (EUR). METHODS: We retrospectively studied the clinical and pathological features of 195 patients who underwent RNU for UTUC. All patients were randomly divided into a training cohort (99 cases) and a validation cohort (96 cases). The training cohort was used to develop nomogram models, and the models were validated by the validation cohort. The least absolute shrinkage and selection operator (LASSO) regression and Cox regression were performed to identify independent predictors. The concordance index (C-index), receiver operator characteristics (ROC) analysis, and calibration plot were used to evaluate the reliability of the models. The clinical utility compared with the pathological T stage was assessed using the net reclassification index (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). RESULTS: SII was an independent risk factor in predicting OS and EUR. The C-index values of the nomogram predicting OS, IVR, and EUR were 0.675, 0.702, and 0.756 in the training cohort and 0.715, 0.756, and 0.713 in the validation cohort. A high level of SII was correlated with the invasion of the mucosa, muscle layer of the ureter, nerves, vessels, and fat tissues. CONCLUSION: We developed nomogram models to predict the OS, IVR, and EUR of UTUC patients. The efficacy of these models was substantiated through internal validation, demonstrating favorable discrimination, calibration, and clinical utility. A high level of SII was associated with both worse OS and shorter EUR-free survival.

The function of Foxp1 represses ß-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity.

Bladder cancer is a common malignant tumor. FOXP1 has been found to be abnormally expressed in tumors such as renal cell carcinoma and endometrial cancer. Here, this investigated the biological roles of Foxp1 in the occurrence and development of bladder cancer. Patients with bladder cancer were obtained from China-Japan Friendship Hospital. Bladder cancer cell lines (5637, UMUC3, J82, and T24 cell) were used in this experiment. Foxp1 mRNA and protein expression levels in patients with bladder cancer were increased, compared with paracancerous tissue (normal). OS and DFS of Foxp1 low expression in patients with bladder cancer were higher than those of Foxp1 high expression. Foxp1 promoted bladder cancer cell growth in vitro model. Foxp1 increased the Warburg effect of bladder cancer. Foxp1 suppressed ß-adrenoceptor (ß-AR) expression in vitro model. ChIP-seq showed that Foxp1 binding site (E1, TTATTTAT) was detected at -2,251 bp upstream of the ß-AR promoter. ß-AR Reduced the effects of Foxp1 on cell growth in vitro model. ß-AR reduced the effects of Foxp1 on the Warburg effect in vitro model by STAT3 activity. Taken together, our findings reveal that Foxp1 promoted the occurrence and development of bladder cancer through the Warburg effect by the activation of STAT3 activity and repressing ß-AR transcription, and which might serve as an important clue for its targeting and treatment of bladder cancer.

Risk factors for extraurothelial recurrence in upper tract urothelial carcinoma after radical nephroureterectomy: a retrospective study based on a Chinese population.

Objectives: The risk factors for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC) are currently inconsistent and unclear. In this study, we aimed to identify these risk factors and develop a grading system for EUR. Methods: We retrospectively analyzed 220 patients who underwent RNU for UTUC in our center from January 2009 to December 2020. Overall survival (OS) and extraurothelial recurrence-free survival (EURFS) were compared using the Kaplan-Meier curve with a log-rank test. Univariate and multivariate Cox regression models were applied to identify the independent risk factors related to EUR. Results: The median follow-up period was 42 (range: 2-143) months. Of the 220 patients, 61 patients developed EUR in our cohort, which had worse survival outcome. Multivariate Cox regression analysis showed pathologic stage, lymph node (LN) status, lymphovascular invasion (LVI), Ki-67, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were independent risk factors for EUR. The Kaplan-Meier curves revealed a significant difference in EUR among the three risk groups. Conclusion: Our study suggests that pathologic stage, LN status, LVI, Ki-67, NLR, and PLR are independent risk factors for EUR in UTUC patients after RNU. The development of a grading system for EUR risk stratification may assist urologists in making clinical decisions regarding the management of UTUC.

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis.

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

A novel nomogram for predicting extraurothelial recurrence in patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: We aimed to establish and validate a nomogram for extraurothelial recurrence (EUR) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). METHODS: The data of 521 patients with UTUC after RNU from 2 medical centers were retrospectively studied and were used as training cohort (n = 301) and external validation cohort (n = 220). We used the least absolute shrinkage and selection operator (LASSO) to select variables for multivariable Cox regression, and included independent risk factors into nomogram models predicting EUR-free survival (EURFS). Multiple parameters were used to validate the nomogram, including the concordance index (C-index), the calibration plots, the time-dependent receiver-operator characteristics curve (ROC), and the decision curve analysis (DCA). Patients were stratified into three risk groups according to total points calculated by nomograms. The differences of EURFS in each group were analyzed by the Kaplan-Meier analysis. RESULTS: Four variables were screened through LASSO regression. Bladder cancer history, Ki-67, lymphovascular invasion (LVI), and pathological T stage were shown to be independent predictive factors for EUR. The C-indexes of the model were 0.793 and 0.793 in training and validation cohorts, respectively. In comparison with prediction based on categorized pathological T stage, the DCA curves for 5-year EUR exhibited better performance. The 5-year EURFS rates were 92.2%, 63.8%, and 36.2% in patients stratified to the low-, medium-, and high-risk group. CONCLUSION: Our study provided a new nomogram to predict the probability of EUR in UTUC patients underwent RNU, with perfect performance in discrimination ability and clinical net benefit. The application of the model may help urologists to choose proper treatment and monitoring.

Development and external validation of a novel nomogram to predict intravesical recurrence after radical nephroureterectomy: a multicenter study.

OBJECTIVE: This study aimed to establish and validate nomograms to predict the probability of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper urinary tract epithelial carcinoma (UTUC). METHODS: Clinical data of 528 patients with UTUC after RNU were collected from two medical centers between 2009 and 2020. We used the least absolute shrinkage and selection operator (LASSO) regression to select variables for multivariable Cox regression analysis in the training cohort and included independent risk factors into nomogram models predicting IVR-free survival (IVRFS). Another center was applied as the external cohort to validate the predictive accuracy and discriminative ability of the nomogram by performing area under the receiver operating curve (AUC), consistency index (C-index), and calibration curve. RESULTS: History of bladder cancer, tumor size, preoperative urine cytology, postoperative instillation, Ki-67, and platelet-to-lymphocyte ratio (PLR) were identified as independent risk factors for IVR. The prognosis model including these predictors demonstrated excellent discriminatory performance in both the training cohort (C-index, 0.814) and external validation cohort (C-index, 0.748). The calibration plots of the nomogram revealed good consistency in both cohorts. Finally, patients could be classified into two risk groups based on scores obtained from the nomogram, with significant differences in IVRFS. CONCLUSION: Our study provided a reliable nomogram for predicting the probability of IVR in patients with UTUC after RNU. Risk stratification based on this model may assist urologists make optimal clinical decisions on the management of UTUC.

Correlation between the timing of diagnostic ureteroscopy for upper tract urothelial cancer and intravesical recurrence after radical nephroureterectomy.

Objective: We aimed to evaluate the effect of the timing of diagnostic ureteroscopy (URS) on intravesical recurrence (IVR) following radical nephroureterectomy (RNU). Patients and methods: The clinical data of 220 patients with upper tract urothelial carcinoma (UTUC) treated with RNU at our center from June 2010 to December 2020 were retrospectively analyzed. According to the timing of the URS, all patients were divided into three groups: the no URS group, the 1-session group (diagnostic URS immediately followed by RNU), and the 2-session group (RNU after diagnostic URS). Additionally, we analyzed IVR-free survival (IVRFS) using the Kaplan-Meier and Cox proportional regression methods. Results: The median follow-up period of these 220 patents was 41 (range: 2-143) months. Among them, 58 patients developed IVR following RNU. Kaplan-Meier curve displayed a significantly higher IVR rate in both treatment groups than in the no-URS group (p=0.025). In the subgroup of patients with renal pelvis cancer, the incidence of IVR was significantly higher in both treatment groups than in the group without URS (p=0.006). In univariate Cox proportional regression analysis, the two treatment groups were risk factors for IVR compared to the no-URS group [p=0.027, hazard ratio (HR): 1.93, 95% confidence interval (CI): 1.08-3.46]. The two-stage group (p=0.032, HR: 1.98, 95% CI: 1.08-3.65), positive urine pathology (p<0.001, HR: 8.12, 95% CI: 3.63-18.15), adjuvant chemotherapy (p<0.001, HR: 0.20, 95% CI: 0.10-0.38), and positive margin (p<0.0001, HR: 7.50, 95% CI: 2.44-23.08) were all identified as independent predictors in the multivariate. Conclusion: This study revealed that delayed RNU following diagnostic URS may increase the risk of postoperative IVR in patients with UTUC, preoperatively positive uropathology, and positive surgical margin were risk factors for IVR after RNU, while early postoperative chemotherapy may effectively prevent IVR. Delay of RUN after URS could increase the risk of IVR.

Prodrug Nanosensitizer Overcomes the Radiation Resistance of Hypoxic Tumor.

Clinical radiation therapy (RT) is often hindered by the low radiation energy absorption coefficient and the hypoxic features of tumor tissues. Among the tremendous efforts devoted to overcoming the barriers to efficient RT, the application of hypoxic radiosensitizers and cell-cycle-specific chemotherapeutics has shown great potential. However, their effectiveness is often compromised by their limited bioavailability, especially in the hypoxic region, which plays a major role in radioresistance. Herein, to simultaneously improve the delivery efficacy of both hypoxic radiosensitizer and cell-cycle-specific drug, a gambogic acid (GA) metronidazole (MN) prodrug (GM) was designed and synthesized based on GA, a naturally occurring chemotherapeutic and multiple pathway inhibitor, and MN, a typical hypoxic radiosensitizer. In combination with MN-containing block copolymers, the prodrug nanosensitizer (NS) of GM was obtained. Owing to the bioreduction of MN, the as-designed prodrug could be efficiently delivered to hypoxic cells and act on mitochondria to cause the accumulation of reactive oxygen species. The strong G2/M phase arrest caused by the prodrug NS could further sensitize treated cells to external radiation under hypoxic conditions by increasing DNA damage and delaying DNA repair. After coadministration of the NS with a well-established tissue-penetrating peptide, efficient tumor accumulation, deep tumor penetration, and highly potent chemoradiotherapy could be achieved.

Intravesical recurrence factors and outcome after radical nephroureterectomy for upper tract urothelial carcinoma: Multivariate analysis with propensity score matching.

Objective: The risk factors for intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) remain inconsistent and unclear. Thus, the risk factors of IVR after RNU and the prognostic significance of the risk indicators were explored herein. Methods: We retrospectively analyzed UTUC patients upon RNU in our center from January 2009 to December 2019. After propensity score matching, 139 patients were included in this study. Univariate and multivariate Cox proportional hazard regressions were used to estimate the hazard ratio and 95% confidence intervals. Overall survival (OS), cancer-specific survival (CSS) and recurrence-free survival (RFS) were measured using the Kaplan-Meier curve with a log-rank test. A P-value < 0.05 was considered statistically significant. Results: We included 139 patients with a median follow-up of 42 months, of which 48 patients had an intravesical recurrence. Multivariate Cox regression analysis showed cytological abnormalities in urine (HR=3.101, P=0.002), hydronephrosis (HR=1.852, P=0.042), adjuvant chemotherapy (HR=0.242, P<0.001), and previous history of bladder cancer (HR=5.51, P<0.001) were independent risk factors for IVR. As for clinical outcomes, OS and CSS suggested disadvantages in patients with IVR compared with patients without recurrence (P=0.042 for OS, P<0.0001 for CSS), OS of patients with abnormal urine cytology and OS and CSS of patients receiving adjuvant chemotherapy did not present clinical significance, and other risk factors all affected the clinical outcome. Conclusion: In this propensity-score matching study, cytological abnormality of urine, hydronephrosis, adjuvant chemotherapy and previous history of bladder cancer were shown to be independent risk factors for IVR. Moreover, risk factors also influence clinical outcomes, thereby rendering it necessary to adopt more active postoperative surveillance and treatment strategies for these patients, which may help improve treatment outcomes.

Bladder cancer selective chemotherapy with potent NQO1 substrate co-loaded prodrug nanoparticles.

Currently, clinical intravesical instillation chemotherapy has been greatly compromised by the toxicological and physiological factors. New formulations that can specifically and efficiently kill bladder cancer cells are in urgent need to overcome the low residence efficiency and dose limiting toxicity of current ones. The combination of mucoadhesive nanocarriers and cancer cell selective prodrugs can to great extent address these limitations. However, the insignificant endogenous stimulus difference between cancer cells and normal cells in most cases and the high local drug concentration make it essential to develop new drugs with broader selectivity-window. Herein, based on the statistically different NQO1 expression between cancerous and normal bladder tissues, the reactive oxygen species (ROS) activatable epirubicin prodrug and highly potent NQO1 substrate, KP372-1, was co-delivered using a GSH-responsive mucoadhesive nanocarrier. After endocytosis, epirubicin could be promptly activated by the NQO1-dependent ROS production caused by KP372-1, thus specifically inhibiting the proliferation of bladder cancer cells. Since KP372-1 is much more potent than some commonly used NQO1 substrates, for example, ß-lapachone, the cascade drug activation could occur under much lower drug concentration, thus greatly lowering the toxicity in normal cells and broadening the selectivity-window during intravesical bladder cancer chemotherapy.

Clinicopathological Features of Papillary Renal Cell Carcinoma With Venous Tumor Thrombus: Case Series from a Large Chinese Center.

Background: Few studies have reported the influence of the histological classification of type-2 papillary renal cell carcinoma (PRCC), which may differ from that of clear cell renal carcinoma (ccRCC), on the prognosis of renal cell carcinoma with tumor thrombus. We investigated the clinicopathological features and prognosis of type-2 PRCC associated with venous tumor thrombi (PRCC-TT). Methods: We retrospectively analyzed 163 patients with renal cell carcinoma with venous tumor thrombus (RCC-TT) admitted to Peking University Third Hospital between June 2016 and June 2020. Twenty-five patients had type-2 PRCC-TT and 138 had ccRCC combined with tumor thrombus; there were 125 males and 38 females. All the included patients underwent radical nephrectomy and thrombectomy under either complete laparoscopic surgery or open surgery. Univariate and multivariate Cox regression analysis were performed to evaluate the prognostic significance of each variable on cancer-specific survival (CSS). Cancer-specific survival was calculated from the date of surgery to death or the last follow-up using the Kaplan-Meier method. Results: The blood vessels of type-2 PRCC-TT presented on CT images were not as abundant as those of ccRCC-TT. Slight enhancement was observed in the corticomedullary phase. While wash-out symptoms were observed, contrast agent extinction was not obvious in the nephrographic and excretory phases. We compared the macroscopic and microscopic appearances of the 2 cohorts. Compared to the ccRCC-TT cohort, lymph node invasion was more prevalent in the PRCC-TT cohort (88.0% vs. 60.9%, P = .009). Multivariate analysis revealed that sarcomatoid differentiation, distant metastasis, and pathological type were the independent predictors of poor CSS. The Kaplan-Meier analysis showed that the CSS of type-2 PRCC-TT and ccRCC-TT were 23.5 and 38.4 months, respectively, with statistical significance (P = .002). Conclusion: Type-2 PRCC-TT varies with common ccRCC-TT in imaging manifestation and pathological characteristics. The prognosis of type-2 PRCC-TT patients was worse than that of ccRCC-TT patients.

Passenger lymphocyte syndrome in renal transplantation: A systematic review of published case reports.

BACKGROUND: Passenger lymphocyte syndrome (PLS) is an immune-mediated hemolysis that occurs after ABO-mismatched kidney transplantation. PLS is caused by donor lymphocytes producing antibodies to recipient red blood cells, resulting in hemolysis. The incidence of PLS has been reported to be approximately 20% in patients with ABO-mismatched groups. Nevertheless, there is no comprehensive review of PLS following renal transplantation. In this review, we systematically summarized the data of patients with PLS after renal transplantation to help clinicians diagnose and treat more effectively. METHODS: A systematic review was conducted using PubMed, Embase, and Web of Science. All relevant data were collected, including age, sex, and clinical and immune parameters. RESULTS: A total of 91 published cases were identified. The age ranged from 9 to 70 years old and 58.2% were male. Eighty-six cases were only kidney transplantations, one was liver-kidney transplantation, three were pancreas-kidney transplantations, and one was intestinal-kidney transplantation. Of these cases, 27 received kidneys from deceased donors, whereas 40 received kidneys from living donors. Most patients showed immune hemolysis dominated by anaemia, which was significantly improved after symptomatic support treatment, such as blood transfusion and erythropoietin injection. CONCLUSION: PLS is an immune-mediated disease that can occur in patients with ABO-mismatched renal transplantation, which commonly causes hemolysis, although death or deformities of the graft can also occur in patients with the disorder. Symptomatic supportive treatment is an effective treatment scheme at present, but more effective treatment and prevention schemes still need to be explored.

lncRNA-UCA1 in the diagnosis of bladder cancer: A meta-analysis.

BACKGROUND: The main purpose of this study is to systematically evaluate the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, and to provide a scientific basis for the diagnosis of bladder cancer. METHODS: By searching PubMed, Web of Science, EMBASE, CNKI, Wanfang, Weipu and other databases, in order to collect relevant literature of lncRNA-UCA1 for diagnosis of bladder cancer. The starting and ending time of the search is from the establishment of the database to December 31, 2019. Screen documents and extract data according to inclusion and exclusion criteria. QUADAS entry tool was used to evaluate the quality of literature. Meta-Disc 1.4 and Stata 12.0 software were used for statistical analysis, and UCA1 was combined for the statistics of bladder cancer diagnosis. RESULTS: A total of 7 articles were included in this study, including 954 cases of bladder cancer patients and 482 cases of non-bladder cancer patients. The receiver operating characteristic curve (ROC) curve AUC of lncRNA-UCA1 used to diagnose bladder cancer was 0.86. The sensitivity was 0.83 (95% CI: 0.80-0.85), and the specificity was 0.86 (95% CI: 0.82-0.89). The positive likelihood ratio is 6.38 (95% CI: 3.01-13.55), and the negative likelihood ratio is 0.20 (95% CI: 0.13-0.31). The diagnostic odds ratio is 33.13 (95% CI: 11.16-98.33). CONCLUSION: lncRNA-UCA1 has a high value of clinical auxiliary diagnosis for bladder cancer, and it can be further promoted and applied clinically.

Single- versus Multiple-Tract Percutaneous Nephrolithotomy in the Surgical Management of Staghorn Stones or Complex Caliceal Calculi: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess current evidence on the effectiveness and safety of single- versus multiple-tract percutaneous nephrolithotomy in the surgical management of complex caliceal calculi or staghorn stones through a comprehensive literature review. METHODS: A comprehensive literature review of articles investigating the clinical efficacy and safety of single- versus multiple-tract percutaneous nephrolithotomy was performed. Relevant literature was obtained by systematically searching PubMed, EMBASE, and the Cochrane Library through May 2020. We followed the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes, including the stone-free rate (SFR), and secondary outcomes (peri- and postoperative complications and operative data) were evaluated using RevMan 5.3 statistical software. RESULTS: Ten studies involving 1844 patients with complex caliceal calculi or staghorn stones met the inclusion criteria. Single-tract percutaneous nephrolithotomy (STPCNL) had noninferior clinical efficacy with respect to the immediate SFR (odds ratio (OR) = 0.80, 95% confidence interval (CI) (0.46 to 1.38), p = 0.42) and 3-month SFR (OR = 1.22, 95% CI (0.38 to 3.92), p = 0.74) compared with multiple-tract percutaneous nephrolithotomy (MTPCNL). In addition, pooled analyses showed that STPCNL resulted in significantly lower hemoglobin decreases (MD = -0.46, 95% CI (-0.68 to -0.25), p < 0.0001), fewer blood transfusions (OR = 0.48, 95% CI (0.34 to 0.67), p < 0.0001), and fewer pulmonary complications (OR = 0.28, 95% CI (0.09 to 0.83), p = 0.02) than MTPCNL. However, the overall evidence was insufficient to suggest a statistically significant difference for other adverse events. CONCLUSION: This meta-analysis indicated that STPCNL is an effective method for treating complex caliceal calculi or staghorn stones. Compared with MTPCNL, STPCNL not only yields similarly high SFRs but also is associated with many advantages, less blood loss, fewer blood transfusions, and fewer pulmonary complications without an increase in other complications. However, the findings of this study should be further confirmed by well-designed prospective randomized controlled trials (RCTs) with a larger patient series.

Angiogenesis related gene expression significantly associated with the prognostic role of an urothelial bladder carcinoma.

BACKGROUND: Bladder urothelial carcinoma (BLCA) is still one of the most malignant diseases and has a dismal outcome. Angiogenesis has confirmed its critical role in the development of malignant neoplasms. In this study, we uncovered the prognostic implications of the angiogenesis-related gene panel in urothelial tumors. METHODS: The RNA-seq data and clinical records of 402 patients with BLCA were collected from the TCGA database. The panel, including 145 genes involved in angiogenesis, was retrieved from the Uniprot database and the published work. The patients with similar expressed profiles were clustered, and the differences in gene expression were compared. The correlation of gene expression and BLCA outcomes or clinical features were analyzed. RESULTS: There were two clusters of BLCA patients identified on the expressed basis of angiogenesis-related genes. A significant difference was detected in the tumor stages between the two clusters (P<0.001) and a striking advantaged prognosis shown in cluster_1 (86.83 vs. 27.06 months, P=0.001). According to statistics, 115 genes showed a discrepancy in expression between the two clusters, and 16 genes positively correlated to tumor stage progression. Separately analyzed the correlation of those stage-related genes and overall survivals (OS) revealed that high expression of 8 genes, including ECM1 (HR =1.72, P<0.001), FN1 (HR =1.564, P=0.004), FGF1 (HR =1.519, P=0.005), FAP (HR =1.449, P=0.020), JAM3 (HR =1.396, P=0.026), THBS1 (HR =1.402, P=0.028), MFGE8 (HR =1.394, P=0.028) and COL8A2 (HR =1.388, P=0.035), were showed worse prognosis of BLCA, respectively. CONCLUSIONS: This study showed an integrated profile of angiogenesis-related genes and identified the different BLCA subgroups with favorable prognosis and poor prognosis depended on the expression pattern of angiogenesis-related genes. Furthermore, this work revealed the single gene expressions of ECM1, FN1, FGF1, FAP, JAM3, THBS1, MFGE8 and COL8A2 involved in angiogenesis associated the prognosis remarkably.

MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression.

MicroRNA-34a (miR-34a) serves as a tumor suppressor in a number of different types of cancer. The present study was performed to investigate the involvement of miR-34a in bladder cancer. In the present study, miR-34a was downregulated in patients with bladder cancer compared with the healthy controls in bladder biopsies and plasma. Downregulation of miR-34a distinguished between patients with bladder cancer and the healthy controls. miR-34a expression was associated with tumor metastasis; however, not with tumor size. Transfection of miR-34a mimics upregulated the expression of phosphatase and tensin homolog (PTEN) in bladder cancer cells, and decreased cell migration and invasion. miR-34a may inhibit bladder cancer cell migration and invasion by upregulating PTEN. miR-34a may additionally serve as a potential therapeutic target for bladder cancer.

One-shot dilation versus serial dilation technique for access in percutaneous nephrolithotomy: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to systematically review the outcomes of the use of one-shot dilation (OSD) and serial tract dilation for percutaneous nephrolithotomy (PCNL). METHODS: A systematic review and meta-analysis was conducted. The randomised controlled trials (RCTs) included in the study were identified from EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials. The last search was performed on 30 April 2018. Summary effects were calculated as risk ratios (RRs) with 95% CIs or mean differences (MDs) with 95% CIs. The endpoints included access time, fluoroscopy time, successful dilation rate, stone-free rate, postoperative decrease in haemoglobin levels, transfusion rate, complication rate and length of postoperative hospital stay. RESULTS: A total of seven RCTs were included in the study, with clinical data reported for 697 patients. The overall access time was approximately 110 s shorter in the OSD group than in the serial dilation group (MD, -110.14; 95% CI -161.99 to -58.30; p<0.0001). The fluoroscopy time was shorter with OSD in all RCTs. In addition, the decrease in postoperative haemoglobin levels was approximately 2.3g/L less in patients in the OSD group than in those in the serial dilation group (MD, -0.23; 95% CI-0.39 to -0.07; p=0.004). No relationship was found between the successful dilation rate, stone-free rate, transfusion rate, or complication rate and the method of tract dilation. CONCLUSION: OSD is a safe and efficacious tract dilation technique that can reduce the access time, fluoroscopy time and postoperative decrease in haemoglobin level. No difference was found in the successful dilation rate, stone-free rate, transfusion rate or rate of complications between the OSD and serial dilation groups. The difference in the length of postoperative hospital stay was uncertain. OSD may be a better method of tract creation for PCNL.