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Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24–30 Fr while maintaining a balloon pressure of 25–35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16–165) with median estimated blood loss of 2 ml (range 0–150). The median postoperative hospital stay was 3 d (range 1–15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3–100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

Abstract Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P

ABSTRACT Background For early detection and postoperative monitoring of upper tract urothelial carcinoma (UTUC), the traditional detection method was limited to its invasiveness and insufficient sensitivity. We aim to use urine tumour DNA (utDNA) for detecting minimal residual disease (MRD), early diagnosis and perioperative monitoring in UTUC. Method We previously established a utDNA multidimensional bioinformatic valuation model, named utLIFE, using low‐coverage whole‐genome sequencing and targeted deep sequencing. This prospective cohort enrolled 93 patients diagnosed with UTUC without metastasis. We collected morning urine samples on the day of surgery and the discharge day after the operation for utLIFE testing. In addition, we also enrolled 80 healthy controls to further validate the specificity of the utLIFE model in the study. Results The utLIFE of preoperative samples could discriminate UTUC with high specificity (96.25%, 77/80), and high sensitivity (96.77%, 90/93) regardless of stage and grade. The sensitivity of utLIFE was significantly higher than urine cytology (p

ABSTRACT Objective: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). Materials and Methods: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. Results: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. Conclusions: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients’ quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.

ABSTRACT Purpose: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. Materials and Methods: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. Results: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. Conclusions: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.

Abstract Laryngopharyngeal reflux disease (LPRD) is a condition characterized by the regurgitation of stomach and duodenal contents into the laryngopharynx, with variable and non-specific symptoms. Therefore, developing an accurate symptom scale for different regions is essential. Notably, the symptoms of “dryness and burning sensation in the laryngopharynx or mouth” are prevalent among the Chinese population but are often omitted from conventional symptom assessment scales, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) scales. To address this gap, our study incorporated the symptoms into the RSI and RSS-12 scales, developing the RSI-10/RSS-13 scales. Afterward, we assessed the role of the new scale’s reliability (Cronbach’s α and test–retest reliability), construct validity (confirmatory factor analysis and confirmatory factor analysis), and diagnostic efficiency. Our study encompassed 479 participants (average = 39.5 ± 13.4 years, 242 female) and 91 (average = 34.01 ± 13.50 years, 44 female) completed 24 h MII-pH monitoring. The Cronbach’s α values of 0.80 and 0.82 for the RSI-10 and RSS-13 scales, respectively. RSI-10 and RSS-13 exhibited strong test–retest reliability (ICCs = 0.82–0.96) and diagnostic efficacy (AUC = 0.84–0.85). Furthermore, the factor analysis identified the RSS-13 and its three sub-scales (ear-nose-throat, digestive tract, respiratory tract) exhibited good to excellent structural validity (χ2/df = 1.95, P

Summary: Background: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. Methods: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. Findings: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. Interpretation: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. Funding: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).

Objective: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. Methods: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone

Abstract. Background:. The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system. Methods:. From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed. Results:. A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively. Conclusion:. The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.

Objective: To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy (rRAPN) with a new robotic platform called KangDuo Surgical Robot-01 (KD-SR-01) system (Suzhou KangDuo Robot Co., Ltd., Suzhou, China) and discuss its surgical technique. Methods: A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney. The R.E.N.A.L. nephrometry score of this patient was 4x. This patient underwent rRAPN with KD-SR-01. The perinephric fat between the tumor and Gerota's fascia was preserved, which was used for internal suspension traction during tumor resection. Postoperative follow-up data were collected. Results: The surgery was successfully carried out with a duration of 127 min, in which the docking time was 6 min 25 s and console time was 60 min. The warm ischemia time was 19 min 53 s, and the estimated blood loss was 0 mL. The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma, with a negative surgical margin. The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade of this patient was Grade 2. No recurrence was observed during the 6-month follow-up. Conclusion: Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.

Abstract Introduction Robotic ureteral reconstruction (RUR) has been widely used to treat ureteral diseases. To summarize the surgical techniques, complications, and outcomes following RUR, as well as to compare data on RUR with open and laparoscopic ureteral reconstruction. Methods Our systematic review was registered on the PROSPERO (CRD42022309364) database. The PubMed, Cochrane and Embase databases were searched for publications in English on 06-Feb-2022. Randomised-controlled trials (RCTs) or non-randomised cohort studies with sample size ≥ 10 cases were included. Results A total of 23 studies were included involving 996 patients and 1004 ureters from 13 non-comparative, and 10 retrospective comparative studies. No RCT study of RUR was reported. The success rate was reported ≥ 90% in 15 studies. Four studies reported 85–90% success rate. Meta-analyses for comparative studies showed that RUR had significantly lower estimated blood loss (EBL) (P = 0.006) and shorter length of stay (LOS) (P

This paper explores the accumulation of Indian astronomical knowledge within Chinese Buddhist scriptures and its dissemination across Chinese society through a comparative study of the Modengjia jing (Ch1 of the ZKA) and the Xiuyao jing (XYJ). The period from the Ch1 of ZKA to the XYJ was a time when Buddhism was in the midst of developing and maturing within China. The Ch1 of the ZKA is regarded as the first Buddhist scripture including a complete account of Indian nakṣatra astrology and translated from Sanskrit parallel text, rather than a native work codified by Buddhists in Ancient China. The XYJ is not a translation but rather an authoritative handbook of Indian astrological knowledge taught by Amoghavajra. A detailed comparison of the contents of the two texts shows that the knowledge contained within Ch1 of the ZKA belongs to the Vedic era and that the XYJ belongs to the post-Vedic era. Beginning with the Ch1 of the ZKA and ending with the XYJ, Buddhist astronomical knowledge steadily grew. Yang Jingfeng’s revision and explanation of the first fascicle of the Sutra reflects Ancient Chinese intellectuals’ acceptance, digestion, and recreation of Buddhist astronomical knowledge. His abandonment of the “Calculation of weekdays” reflects the influence of the Chinese mathematical and astronomical tradition and the calendar tradition upon his perspective; perhaps this is one of the reasons why China has accepted the weekday within daily life up to the modern era. Every civilization, in learning to assimilate other cultures, has a choice between foreignization and domestication, within which a tension is reflected. Learning from foreign cultures is about keeping up with the most advanced civilizations in the world and advancing with the times, while maintaining one’s own cultural identity and cultural characteristics is necessary for one’s own civilization; these two notions are complementary and should not be neglected.

Background: Pelvic lipomatosis (PL) is a rare condition that is characterized by excessive growth of fat in the pelvic cavity. Studies have yet to systematically review surgical treatments for PL. Objectives: To provide a reference for selecting reasonable surgical treatments for PL patients according to previous literature on the surgical treatment of PL. Design and methods: We conducted this systematic review in accordance with the Preferred Reporting Items for a Systematic Review and Meta-Analysis (PRISMA) of Individual Participant Data guidelines. Literature on PL published from 1968 to 2022 was retrieved from the PubMed and EMBASE databases. Data were collected and analyzed independently by two independent investigators. Results: A total of 42 studies, involving 231 patients with PL, were included in the analysis. The surgical treatments included transurethral resection (TUR) (48.5%), ureteral stent placement (11.7%), percutaneous nephrostomy (1.3%), ureterocutaneostomy (1.3%), ureteral reimplantation (10.4%), ileal conduit (13%), and allograft kidney transplantation (0.4%). After excluding patients with unclear prognoses, 42.9% of patients showed improvement in lower urinary tract symptoms (LUTS) after TUR. Ureteral stent placement provided relief of hydronephrosis in 62.5% of PL patients. Percutaneous nephrostomy resulted in stable renal function in 33.3% of PL patients, while ureterocutaneostomy led to remission of postoperative hydronephrosis in 33.3% of PL patients. After ureteral reimplantation, 70.8% of patients experienced relief of hydronephrosis or had stable renal function. Ileal conduit led to remission of hydronephrosis, alleviation of symptoms, or maintenance of stable renal function in 83.3% of PL patients. One patient with PL had stable renal function after allograft renal transplantation. Conclusion: The surgical treatments for PL include TUR, ureteral stent placement, urinary diversion, and allograft renal transplantation. However, the choice of surgical method should be determined after comprehensive consideration of the patient’s condition.

Renal cell carcinoma (RCC) is one of the most malignant urological tumors. Currently, there is a lack of molecular markers for early diagnosis of RCC. The 5-year survival rate for early-stage RCC is generally favorable; however, the prognosis takes a significant downturn when the tumor progresses to distant metastasis. Therefore, the identification of molecular markers for RCC is crucial in enhancing early diagnosis rates. Exosomes are a type of extracellular vesicle (EV) typically ranging in size from 30 nm to 150 nm, which contain RNA, DNA, proteins, lipids, etc. They can impact neighboring receptor cells through the autocrine or paracrine pathway, influence cellular communication, and regulate the local immune cells, consequently shaping the tumor immune microenvironment and closely associating with tumor development. The clinical application of exosomes as tumor markers and therapeutic targets has ignited significant interest within the research community. This review aims to provide a comprehensive summary of the advancements in exosome research within the context of RCC.

The coronavirus disease 2019 pandemic has drawn attention to telesurgery. Important advances in fifth-generation (5G) mobile telecommunication technology have facilitated the rapid evolution of telesurgery. Previously, only a single console was used in telesurgery; thus, there was the possibility of open or laparoscopic conversion. Furthermore, the 5G network has not been available for regional hospitals in China. From October 2021 to April 2022, dual-console telesurgeries with the KangDuo Surgical Robot-01 (KD-SR-01) system were performed using 5G and wired networks in an animal experiment and clinical study. A partial nephrectomy in a porcine model was performed successfully using a wired network. The console time, warm ischemia time, and control swap time were 69 min, 27 min, and 3 s, respectively. The mean latency time was 130 (range, 60–200) ms. A 32-yr-old male patient successfully underwent a remote pyeloplasty using a series connection of 5G wireless and wired networks. The console time and control swap time were 98 min and 3 s, respectively. The mean latency time was 271 (range, 206–307) ms. In the two studies, data pocket loss was

PURPOSETo evaluate the feasibility and usefulness of cine magnetic resonance urography (cine MRU) as a novel postoperative examination after upper urinary tract reconstruction surgery.METHODSNinety-six patients underwent cine MRU for postoperative evaluation between August 2015 and August 2020. The morphological observations included regular peristalsis, anastomosis, urine flow signals, and reflux. The quantitative evaluations included luminal diameter, peristaltic amplitude, contraction ratio, peristaltic waves, and ureteric jets. The surgical outcomes were classified as success, gray area, or failure by combining the results of cine MRU, symptoms, and the degree of hydronephrosis.RESULTSThere was no obvious stenosis of the anastomosis in 83 patients (86.46%). Regular peristalsis of the ureter and signals of urination was observed in 85 (88.54%) and 84 patients (87.50%), respectively. In addition, three patients (3.13%) showed urine reflux. The patients in both the success group and the gray area group showed significantly different creatinine levels (success 86.2 ± 22.3 μmol/L vs. failure 110.7 ± 8.2 μmol/L, P = 0.016; gray area 81.0 ± 20.0 μmol/L vs. failure 110.7 ± 8.2 μmol/L, P = 0.009) and estimated glomerular filtration rate (success: 88.5 ± 23.1 mL/min·1.73 m2, failure: 61.6 ± 14.1 mL/min·1.73 m2, P = 0.014; gray area: 94.7 ± 24.6 mL/min·1.73 m2, failure: 61.6 ± 14.1 mL/min·1.73 m2, P = 0.007) compared to those in the failure group. The ipsilateral split renal function was 33.6 ± 15.0, 24.5 ± 13.4, and 20.1 ± 0.4 mL/min in the success, gray area, and failure groups, respectively (P = 0.354).CONCLUSIONCine MRU demonstrates the morphology and function of the reconstructed upper urinary tract. The results of cine MRU can be used to evaluate the surgical effect, providing guidance for further treatment.

Abstract Background Complete intracorporal robotic ileal ureteric replacement is challenging. We aimed to present the surgical technique of robotic ileal ureter replacement with extracorporeal ileal segment preparation for long ureteral strictures. Methods From March 2019 to March 2021, 18 patients underwent robotic ileal ureter replacement with extracorporeal ileal segment preparation by one experienced surgeon. The demographic, perioperative, and follow-up data were recorded. Success was defined as the resolution of the presenting symptom, a stable estimated glomerular filtration rate and unobstructive drainage on imaging examination. Results All 18 surgeries were successfully completed without conversion. The median length of the intestinal tube used was 20 (12–30) cm. The median operative time was 248 (170–450) min, the median estimated blood loss was 50 (10–200) ml, and the median postoperative hospital stay was 7 (5–27) days. At a median follow-up of 16 (13–28) months, all patients were symptom-free. No or mild hydronephrosis was confirmed in 17 patients; 1 patient had moderate hydronephrosis without peristalsis of the ileal ureter. The renal function was stable in all patients. The overall success rate was 100%. Postoperative complications, including 4 cases of urinary infections (Grade I), 1 case of an incision hernia (Grade I), 4 cases of kidney stone formation (Grade I), 6 cases of metabolic acidosis (Grade I), 4 cases of incomplete ileus (Grade II), and 1 case of an incision infection (Grade IIIb). Conclusions Robot-assisted laparoscopic ileal ureter replacement with extracorporeal ileal segment preparation is safe, feasible, and effective for the treatment of long ureteral strictures, especially in high-volume tertiary referral centers with extensive robotic surgery experience capable of managing severe peri-operative complications.

Background: Homologous Recombination Repair (HRR) is the most reliable and important signaling pathway for repairing DNA damage. We initiated a calibration project to better understand the NGS landscape for HRR gene testing in China, provide indications for testing standardization, and guide clinical practice. Methods: A questionnaire was used to collect laboratory information, panel design for HRR gene testing, tissue sample test parameters, plasma ctDNA sample test parameters, and procedures for variant interpretation. The testing quality of the participating laboratories was further evaluated by external quality assessment (EQA), which provided 5 FFPE slices and 5 mimic ctDNA samples as standard references for evaluation. Test results and reports were collected to assess laboratory performance. Results: Our results showed that different laboratories had significant differences in sequencing platforms, library construction technologies, genes in the testing panel, detectable mutation types, probe coverage regions, sequencing parameters, variants interpretation guidelines, and positive test rates. For the EQA test, the overall pass rate was about 60%. The average accuracy for tissue samples and ctDNA samples was 79.55% and 74.13%, respectively. It is worth noting that variants in tandem repetition regions and splice sites, and those with low allele frequency were more prone to misdetection. The most common reasons for misdetection were as follows: the testing panel did not cover the genes or the whole exon and splice sites of the genes; the variants were misclassified as benign or likely benign, and the variants failed the QC criteria. Conclusions: The discrepancies observed in our survey and EQA test affect the authenticity of HRR gene test results for prostate cancer, underlining the need to establish guidelines for HRR gene testing and variant interpretation in China, and to optimize HRR gene testing in clinical practice to improve management and patient care.

Immunotherapy has ushered in a new era in cancer treatment, and cancer immunotherapy continues to be rejuvenated. The clinical goal of cancer immunotherapy is to prime host immune system to provide passive or active immunity against malignant tumors. Tumor infiltrating leukocytes (TILs) play an immunomodulatory role in tumor microenvironment (TME) which is closely related to immune escape of tumor cells, thus influence tumor progress. Several cancer immunotherapies, include immune checkpoint inhibitors (ICIs), cancer vaccine, adoptive cell transfer (ACT), have shown great efficacy and promise. In this review, we will summarize the recent research advances in tumor immunotherapy, including the molecular mechanisms and clinical effects as well as limitations of immunotherapy.

Abstract Background Clear cell renal cell carcinoma (ccRCC) is characterized by the accumulation of lipid-reactive oxygen species. Ferroptosis, due to the lipid peroxidation, has been reported to be strongly correlated with tumorigenesis and progression. However, the functions of the ferroptosis process in ccRCC remain unclear. Methods After sample cleaning, data integration, and batch effect removal, we used the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases to screen out the expression and prognostic value of ferroptosis-related lncRNAs and then performed the molecular subtyping using the K-means method. Then, the functional pathway enrichment and immune microenvironment infiltration between the different clusters were carried out. The results showed a significant difference in immune cell infiltration between the two clusters and the associated marker responded to individualized differences in treatment. Then, least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a prognostic signature based on 5 lncRNAs. This signature could accurately predicted patient prognosis and served as an independent clinical risk factor. We then combined significant clinical parameters in multivariate Cox regression and the prognostic signature to construct a clinical predictive nomogram, which provides appropriate guidance for predicting the overall survival of ccRCC patients. Results The prognostic differentially expressed ferroptosis-related LncRNAs (DEFRlncRNAs) were found, and 5 lncRNAs were finally used to establish the prognostic signature in the TCGA cohort, with subsequently validation in the internal and external cohorts. Moreover, we conducted the molecular subtyping and divided the patients in the TCGA cohort into two clusters showing differences in Hallmark pathways, immune infiltration, immune target expression, and drug therapies. Differences between clusters contributed to individualizing treatment. Furthermore, a nomogram was established to better predict the clinical outcomes of the ccRCC patients. Conclusions Our study conducted molecular subtyping and established a novel predictive signature based on the ferroptosis-related lncRNAs, which contributed to the prognostic prediction and individualizing treatment of ccRCC patients.

Abstract Background Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. Methods First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. Results The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. Conclusions Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.

Abstract Background At present, the extent and clinical relevance of epigenetic differences between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) remain largely unknown. Here, we conducted a study to describe the global DNA methylation landscape of UTUC and UCB and to address the prognostic value of DNA methylation subtype and responses to the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma (UC). Methods Using whole-genome bisulfite sequencing (n = 49 samples), we analyzed epigenomic features and profiles of UTUC (n = 36) and UCB (n = 9). Next, we characterized potential links between DNA methylation, gene expression (n = 9 samples), and clinical outcomes. Then, we integrated an independent UTUC cohort (Fujii et al., n = 86) and UCB cohort (TCGA, n = 411) to validate the prognostic significance. Furthermore, we performed an integrative analysis of genome-wide DNA methylation and gene expression in two UC cell lines following transient DNA methyltransferase inhibitor SGI-110 treatment to identify potential epigenetic driver events that contribute to drug efficacy. Results We showed that UTUC and UCB have very similar DNA methylation profiles. Unsupervised DNA methylation classification identified two epi-clusters, Methy-High and Methy-Low, associated with distinct muscle-invasive statuses and patient outcomes. Methy-High samples were hypermethylated, immune-infiltrated, and enriched for exhausted T cells, with poor clinical outcome. SGI-110 inhibited the migration and invasion of Methy-High UC cell lines (UMUC-3 and T24) by upregulating multiple antitumor immune pathways. Conclusions DNA methylation subtypes pave the way for predicting patient prognosis in UC. Our results provide mechanistic rationale for evaluating SGI-110 in treating UC patients in the clinic.

Abstract Introduction To describe our initial experience with ileal ureteral replacement (IUR) for the management of ureteral avulsion (UA) during ureteroscopic lithotripsy. Methods Between September 2010 and April 2021, ten patients received ileal ureteral replacement for ureteral avulsion during ureteroscopic lithotripsy. Anterograde urography and computed tomography urography (CTU) were applied to evaluate the lesion. Follow-up was performed with magnetic resonance urography and renal ultrasound as well as clinical assessment of symptoms. We retrospectively analysed the clinical data of ten patients treated with ileal ureteral replacement for the treatment of ureteral avulsion. Results Four patients underwent open ileal ureteral replacement, two underwent laparoscopic ileal ureteral replacement, and four underwent robotic-assisted ileal ureteral replacement. The mean operative time (OT) was 310 min (range 191–530). The mean estimated blood loss (EBL) was 193 mL (range 10–1000). The mean length of the ileal graft was 21 cm (range 12–25). The median postoperative hospital time was 13 days (range 7–19). All surgeries were effectively completed, and no case required open conversion in laparoscopic and robotic-assisted surgeries. There was no obvious hydronephrosis according to contrast-enhanced computed tomography 3-dimensional reconstruction images without serious complications or progressive hydronephrosis during a median follow-up duration of 51 months (range 5–131), and the success rate was 100%. Conclusions Our initial results and experience showed that ileal ureteral replacement for the management of ureteral avulsion during ureteroscopic lithotripsy is safe and feasible.

Purpose: To evaluate the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) detection via target biopsy (TB), systematic biopsy (SB), and combined biopsy (CB) in patients with PI-RADS 5 lesions. Methods: Patients with at least one PI-RADS 5 lesion were retrospectively enrolled in a prospectively collected database. The patients underwent multiparametric magnetic resonance imaging (mpMRI) followed by transrectal TB of PI-RADS 5 lesions and SB. The PCa and CSPCa detection rates and cores of TB and SB were compared with those of CB. Results: In 585 patients, prostate biopsy revealed PCa in 560 cases (95.73%) and CSPCa in 549 cases (93.85%). PCa was detected in T2 patients (93.13%, 217/233) and in T3/4 patients (97.44%, 343/352). CSPCa was detected in T2 patients (89.27%, 208/233) and in T3/4 patients (96.87%, 341/352). The positive rates of TB for T2/3/4, T3/4, and T2 were 94.02%, 96.21%, and 90.56%, respectively. SB added 1.71% (10/585) PCa and 1.37% (8/585) CSPCa detection to TB. There was no difference between TB and SB in detecting different stages of cancer (p > 0.05). In the biopsy core analysis, TB had fewer biopsy cores and a higher detection rate than SB (all p < 0.05). Conclusions: In patients with PI-RADS score 5 lesions, TB can achieve the same detection rate as, with fewer biopsy cores than, CB. SB adds minimal clinical value and can be omitted for these patients.

Background: Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported. Methods: Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU–BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo. Results: The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 (PD-1)/programmed death ligand 1 (PD-L1)/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy. Conclusions: These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa.

Summary: Background: Current methods for the detection and surveillance of urothelial carcinomas (UCs) are often invasive, costly, and not effective for low-grade, early-stage, and minimal residual disease (MRD) tumors. We aimed to develop and validate a model from urine sediments to predict different grade and stage UCs with low cost and high accuracy. Methods: We collected 167 samples, including 90 tumors and 77 individuals without tumors, as a discovery cohort. We assessed copy number variations and methylation values for them and constructed a diagnostic classifier to detect UC, UCseek, by using an individual read-based method and support vector machine. The performance of UCseek was validated in an independent cohort derived from three hospitals (n = 206) and a relapse cohort (n = 42) for monitoring recurrence. Findings: We constructed UCseek, which could predict UCs with high sensitivity (92.7%), high specificity (90.7%), and high accuracy (91.7%) in the independent validation set. The accuracy of UCseek in low-grade and early-stage patients reached 91.8% and 94.3%, respectively. Notably, UCseek retained great performance at ultralow sequencing depths (0.3X-0.5X). It also demonstrated a powerful ability to monitor recurrence in a surveillance cohort compared with cystoscopy (90.91% vs. 59.09%). Interpretation: We optimized an improved approach named UCseek for the noninvasive diagnosis and monitoring of UCs in both low- and high-grade tumors and in early- and advanced-stage tumors, even at ultralow sequencing depths, which may reduce the burden of cystoscopy and blind second surgery. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgments section.

BackgroundsDespite the genomic landscape of urothelial carcinomas (UC) patients, especially those with UC of bladder (UCB), has been comprehensively delineated and associated with pathogenetic mechanisms and treatment preferences, the genomic characterization of upper tract UC (UTUC) has yet to be fully elucidated.Materials and methodsA total of 131 Chinese UTUC (74 renal pelvis & 57 ureter) and 118 UCB patients were enrolled in the present study, and targeted next-generation sequencing (NGS) of 618 cancer-associated genes were conducted to exhibit the profile of somatic and germline alterations. The COSMIC database, including 30 mutational signatures, were utilized to evaluate the mutational spectrums. Moreover, TCGA-UCB, MSKCC-UCB, and MSKCC-UTUC datasets were retrieved for preforming genomic alterations (GAs) comparison analysis between Western and Chinese UC patients.ResultsIn our cohort, 93.98% and 56.63% of UC patients were identified with oncogenic and actionable somatic alterations, respectively. Meanwhile, 11.24% of Chinese UC patients (of 14.50% and 7.63% of UTUC and UCB cases, respectively) were identified to harbor a total of 32 pathogenic/likely-pathogenic germline variants in 22 genes, with DNA damage repair (DDR)-associated BRCA1 (1.20%) and CHEK2 (1.20%) being the most prevalent. Chinese UTUC and UCB patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in KMT2D/C/A, GNAQ, ERCC2, RB1, and PPM1D. In addition, we also found notable differences in the prevalence of ELF3, TP53, PMS2, and FAT4 between renal pelvis and ureter carcinomas. Moreover, 22.90% and 33.90% of UTUC and UCB patients, respectively, had at least one deleterious/likely deleterious alteration in DDR related genes/pathways. Subsequently, mutational signature analysis revealed that UC patients with mutational signature 22, irrespective of UTUC or UCB, consistently had the markedly higher level of tumor mutational burden (TMB), which was proved to be positively correlated with the objective complete/partial response rate in the IMvigor210 cohort. By comparison, Chinese and Western UTUC patients also differed regrading GAs in oncogenic-related genes/pathways, especially in TP53, RTK/RAS, and PI3K pathways; besides, more alterations in WNT pathway but less TP53, RTK/RAS, HIPPO, and PI3K pathways were identified in Chinese UCB.DiscussionsThe in-depth analysis of genomic mutational landscapes revealed distinct pathogenetic mechanisms between Chinese UTUC and UCB, and specific genomic characterizations could identify high risk population of UTUC/UCB and provided information regarding the selection of alternative therapeutic regimens.

Urinary tract infection with mixed microorganisms may lead to false-positive resistance detection. Current antimicrobial susceptibility testing (AST) performed in clinical laboratories is based on bacterial culture and takes a long time for mixed bacterial infections. Here, we propose a machine learning-based single-cell metabolism inactivation concentration (ML-MIC) model to achieve rapid AST for mixed bacterial infections. Using E. coli and S. aureus as a demonstration of mixed bacteria, we performed feature extraction and multi-feature analysis on stimulated Raman scattering (SRS) images of bacteria with the ML-MIC model to determine the subtypes and AST of the mixed bacteria. Furthermore, we assessed the AST of mixed bacteria in urine and obtained single-cell metabolism inactivation concentration in only 3 ​h. Collectively, we demonstrated that SRS imaging of bacterial metabolism can be extended to mixed bacterial infection cases for rapid AST.

BackgroundIn bladder and breast cancer, the claudin-low subtype is widely identified, revealing a distinct tumor microenvironment (TME) and immunological feature. Although we have previously identified individual claudin members as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC), the existence of an intrinsic claudin-low subtype and its interplay with TME and clinical outcomes remains unclear.MethodsTranscriptomic and clinical data from The Cancer Genome Atlas (TCGA)- kidney clear cell carcinoma (KIRC) cohort and E-MTAB-1980 were derived as the training and validation cohorts, respectively. In addition, GSE40435, GSE53757, International Cancer Genome Consortium (ICGC) datasets, and RNA-sequencing data from local ccRCC patients were utilized as validation cohorts for claudin clustering based on silhouette scores. Using weighted correlation network analysis (WGCNA) and multiple machine learning algorithms, including least absolute shrinkage and selection operator (LASSO), CoxBoost, and random forest, we constructed a claudin-TME related (CTR) risk signature. Furthermore, the CTR associated genomic characteristics, immunity, and treatment sensitivity were evaluated.ResultsA claudin-low phenotype was identified and associated with an inferior survival and distinct TME and cancer immunity characteristics. Based on its interaction with TME, a risk signature was developed with robust prognostic prediction accuracy. Moreover, we found its association with a claudin-low, stem-like phenotype and advanced clinicopathological features. Intriguingly, it was also effective in kidney chromophobe and renal papillary cell carcinoma. The high CTR group exhibited genomic characteristics similar to those of claudin-low phenotype, including increased chromosomal instability (such as deletions at 9p) and risk genomic alterations (especially BAP1 and SETD2). In addition, a higher abundance of CD8 T cells and overexpression of immune checkpoints, such as LAG3, CTLA4 and PDCD1, were identified in the high CTR group. Notably, ccRCC patients with high CTR were potentially more sensitive to immune checkpoint inhibitors; their counterparts could have more clinical benefits when treated with antiangiogenic drugs, mTOR, or HIF inhibitors.ConclusionWe comprehensively evaluated the expression features of claudin genes and identified a claudin-low phenotype in ccRCC. In addition, its related signature could robustly predict the prognosis and provide guide for personalizing management strategies.

Rapid identification and antimicrobial susceptibility testing (AST) of bacteria are key interventions to curb the spread and emergence of antimicrobial resistance. The current gold standard identification and AST methods provide comprehensive diagnostic information but often take 3 to 5 days. Here, a compound Raman microscopy (CRM), which integrates Raman spectroscopy and stimulated Raman scattering microscopy in one system, is presented and demonstrated for rapid identification and AST of pathogens in urine. We generated an extensive bacterial Raman spectral dataset and applied deep learning to identify common clinical bacterial pathogens. In addition, we employed stimulated Raman scattering microscopy to quantify bacterial metabolic activity to determine their antimicrobial susceptibility. For proof-of-concept, we demonstrated an integrated assay to diagnose urinary tract infection pathogens, S. aureus and E. coli. Notably, the CRM system has the unique ability to provide Gram-staining classification and AST results within ~3 h directly from urine samples and shows great potential for clinical applications.

Abstract Background To present the experience with the surgical management of ureteral endometriosis (UE) in our single center. Methods To present the experience with the surgical management of ureteral endometriosis (UE) in our single center. A retrospective analysis of 40 patients with UE who presented with intraoperative surgical findings of endometriosis involving the ureter and pathology-proven UE was performed. Results Forty patients (median age, 42.5 years) with histological evidence of UE were included. Six (15%) patients had a history of endometriosis. Twenty-one (52%) patients had urological symptoms, and 19 (48%) patients were asymptomatic. All patients had hydronephrosis. The mean glomerular filtration rate (GFR) of the ipsilateral kidney was significantly worse than that of the contralateral kidney (23.4 vs 54.9 ml/min; P

The story of Śārdūlakarṇāvadāna consists of stories of the present life and past life. The former is about a girl from the low-caste Mātaṅga tribe who pursues Ananda, a disciple of the Buddha, but her pursuit ends in vain, and she eventually converts to Buddhism. The latter is about a low-caste king demonstrating his knowledge of the Vedas and astrology in a bid to marry the daughter of a great Brahmin for his son. The story could be seen in various Buddhist texts, such as the Divyavadāna from Nepal and the Mātaṅga Sutra in China. This paper studies the narration and logic of Śārdūlakarṇāvadāna stories, and it makes conclusions on the commonalities in the compilation of Buddhist narratives by analyzing the beginning and end of the story, as well as its narrator, narratee, and the four conflicts (i.e., the caste barriers, the violation of precepts, the use of incantations, and the use of expertise in seeking marriage).

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database.Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses.Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system.Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.

Abstract Prostate cancer (PCa) is a complex disease. An ongoing accumulation of mutations results in increased genetic diversity, with the tumor acquiring distinct subclones. However, non‐genetic intra‐tumoral heterogeneity, the cellular differentiation state and the interplay between subclonal evolution and transcriptional heterogeneity are poorly understood. Here, the authors perform single‐cell RNA sequencing from 14 untreated PCa patients. They create an extensive cell atlas of the PCa patients and mapped developmental states onto tumor subclonal evolution. They identify distinct subclones across PCa patients and then stratify tumor cells into four transcriptional subtypes, EMT‐like (subtype 0), luminal A‐like (subtype 1), luminal B/C‐like (subtype 2), and basal‐like (subtype 3). These subtypes are hierarchically organized into stem cell‐like and differentiated status. Strikingly, multiple subclones within a single primary tumor present with distinct combinations of preferential subtypes. In addition, subclones show different communication strengths with other cell types within the tumor ecosystem, which may modulate the distinct transcriptional subtypes of the subclones. Notably, by integrating TCGA data, they discover that both tumor cell transcriptional heterogeneity and cellular ecosystem diversity correlate with features of a poor prognosis. Collectively, their study provides the analysis of subclonal and transcriptional heterogeneity and its implication for patient prognosis.

BackgroundNumerous studies have investigated the risk factors of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC). However, few studies explore the predictors for unfavorable pathological types of IVR following RNU.MethodsWe retrospectively reviewed 155 patients diagnosed with bladder cancer (BC) following RNU. Binary logistic regression was used for the univariable and multivariable analyses. Nomograms were developed based on the multivariable analysis. The concordance index (C-index) was used to assess the performance of the nomograms. We performed internal validation by generating calibration plots.ResultsMuscle-invasive BC (MIBC) was significantly correlated with operation interval (p = 0.004) and UTUC T-stage (p = 0.016). Operation interval (p = 0.002) and UTUC T-stage (p = 0.028) were also risk factors for BC > 3 cm. UTUC grade (p = 0.015), operation interval (p = 0.003), and hydronephrosis (p = 0.049) were independent predictors for high-grade BC (HGBC). MIBC (p = 0.018) and surgical approach (p = 0.003) were associated with multifocal IVR. Besides, MIBC and HGBC were associated with UTUC grade (p = 0.009), operation interval (p = 0.001), and hydronephrosis (p = 0.023). Moreover, only operation interval (p = 0.036) was a predictor for BC with at least one unfavorable pathological type. We developed nomograms for MIBC, HGBC, BC > 3 cm, and MIBC and/or HGBC. The calibration curves of the nomograms showed good agreement between the observation and prediction cases. The C-indexes of the nomograms were 0.820 (95% CI, 0.747–0.894), 0.728 (95% CI, 0.649–0.809), 0.770 (95% CI, 0.679–0.861), and 0.749 (95% CI, 0.671–0.827), respectively.ConclusionsThe current study found that operation interval, UTUC T-stage, UTUC grade, surgical approach, and hydronephrosis are independent predictors for unfavorable pathological types of IVR following RNU. Nomograms based on these predictors were developed and internally validated to assess the risk of developing unfavorable pathological types of IVR. Furthermore, patients at high risk of developing unfavorable pathological types BC may benefit from more active follow-up 1 year after RNU by early detection of IVR.

Abstract Background Distal tibial tuberosity high tibial osteotomy (DTT-HTO) can prevent distalization of the tibial tuberosity and thus patellar infera. However, no studies on the clinical and radiological effects of DTT-HTO on the patellofemoral joint have been conducted. The purpose of the study was to evaluate the effect of DTT-HTO on patella height and patellofemoral joint congruity based on the severity of patellofemoral joint OA. Methods Twenty-nine patients (33 knees) who underwent DTT-HTO and second-look arthroscopy when implant was removed between January 2018 and May 2020 were eligible for the study. Among them, 6 were males, and 23 were females, with ages from 51 to 78 years old. The Caton-Deschamps index (CDI), congruence angle (CA), and lateral patellar tilt (LPT) were measured to evaluate the effect of surgery on patellar height and patellofemoral joint congruity. The weight-bearing line ratio (WBLR) was measured to assess lower limb alignment. The cartilage lesion in the patellofemoral joint was assessed arthroscopically during surgery and implant removal by the International Cartilage Repair Society (ICRS) grading system at 18–24 months after surgery. The Hospital for Special Surgery (HSS) scale was used to evaluate knee joint function. Results Twenty-nine patients were followed up for 18–28 months. The preoperative CDI, CA, and LPT changed from 0.92 ± 0.16 to 0.89 ± 0.14, from 5.52 ± 2.19 to 5.44 ± 2.27, and from 6.95 ± 2.88 to 6.54 ± 2.42, respectively, and the differences were not statistically significant (p > 0.05). The preoperative WBLR significantly increased from 16.72 ± 6.77 to 58.77 ± 7.69% (p < 0.001). The cartilage lesions in the patella and femoral trochlea did not progress significantly from the first- to the second-look arthroscopy, according to the ICRS grades (p > 0.05). The HSS score significantly improved from 50.64 ± 19.18 preoperatively to 67.33 ± 14.72, 81.63 ± 11.92, and 82.73 ± 8.05 at the 3-month, 12-month, and last follow-up after surgery (p < 0.001). Conclusion DTT-HTO can effectively prevent patellar infera, and its effects on postoperative patellofemoral joint congruity and patellofemoral joint OA progression are inconspicuous. It can be recommended as a treatment of varus knee combined with patellar infera or patellofemoral joint OA.

Abstract Purpose This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations. Methods Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations. Results A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3–4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001). Conclusions Multifocality, T3–4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

Objective: To grasp the general situation of Chinese urological surgeons and the status quo of their scientific research, work and training, thus providing valuable recommendations for urological talent team construction in future. Methods: The survey respondents were the urological surgeons, who held the Certificate of Medical Practitioner in the People's Republic of China, whose scope of practice was confined to urological surgery. The urological surgeons involved in the project completed an online questionnaire survey. All the data were collected through the internet. Results: There were a total of 18 981 urological surgeons in China in 2015, of whom 15 875 from 2 602 hospitals participated in this project, with a mean age of 39.64 years old. In 2015, 1 949 631 cases of surgery were performed, including 493 723 cases of open surgery, 1 146 444 cases of endoscopic/laparoscopic surgery (robot-assisted laparoscopic surgery were excluded), 6 259 robot-assisted surgery and other types of urological surgery. Besides, Chinese urological surgeons published 1 358 monographs as well as 14 558 academic papers, and also obtained 2 064 scientific funds in 2015. A total of 92 122 person-time participated in academic conferences. Urological surgeons with higher educational degrees as well as higher academic titles and from Eastern China or higher-level hospitals had more opportunities to participate in further education and training. Conclusion: This is the very first census conducted through internet on urological surgeons' multiple aspects. After analyzing and summarizing the data collected, the Census could improve the quality of urological diseases diagnosis and treatment in China. Keywords: Census, Surgeons, Hospitals, Surgery, Education, Laparoscopy, Endoscopy

Abstract Background Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.

ObjectivesTo summarize the clinicopathological diagnostic features and evolutionary trends of upper tract urothelial carcinoma (UTUC) in China over the past 20 years.MethodsAll patients diagnosed with upper tract urothelial carcinoma in the Peking University First Hospital from 2001 to 2020 were retrospectively collected. Data were divided into two groups (2001-2010 and 2011-2020) according to the date of diagnosis. Statistical analysis was done with the SPSS V22.0. Chi-square analysis and t-test were adopted to analyze depending on the data type. Subgroup analysis based on 5 years was used for visualization to present trends. Both Kaplan-Meier curve and Cox regression were used for univariate and multivariate survival analysis.ResultsThe study included 2561 cases diagnosed with upper tract urothelial carcinoma in total. Compared with the first decade (2001-2010), patients of the second decades (2011-2020) had elder mean age (66.65 versus 67.59, years, p=0.025), higher male proportion (43.5% versus 49.0%, p=0.034), lower incidence of renal pelvic tumors (53.4% versus 45.8%, p

ObjectiveWhole-exon sequencing (WES) is a commercially available tool for hereditary disease testing. However, little is known about hereditary upper-tract urothelial carcinoma (UTUC) in the Chinese population. This study aims to investigate the prevalence of Lynch syndrome (LS) in UTUC patients with high-risk features and identify the germline mutations of genetic predisposition gene mutations in those patients.MethodsIn total, 354 consecutive UTUC patients undergoing surgery were universally recruited, of whom 108 patients under 60 years old or with a personal/family history of cancer underwent universal immunohistochemistry staining to detect the expression of mismatch repair (MMR) proteins (MLH1, MSH2, MSH6 and PMS2). Patients with deficient or weak MMR protein staining or meeting the Amsterdam II criterion were defined as suspected LS patients, who further experienced microsatellite instability (MSI) (BAT25, BAT26, BAT40, D2S123, D5S346, D17S250) detection and performed WES analysis to explore germline pathogenic/likely pathogenic (P/LP) alterations.ResultsOf 108 patients, 90 (83.3%) cases were included due to younger than 60 years, and 18 cases due to personal/family history. IHC staining identified 21 patients with deficient MMR protein staining and 15 cases with weak MMR protein staining. Three cases met the Amsterdam II criterion but with proficient MMR protein staining. Finally, WES analysis was performed in 38 suspected LS patients and P/LP germline mutations were identified in 22 individuals. Genetic testing confirmed 5 LS cases, including 3 cases with novel mutations. MSI-harboring tumor was discovered in 4 LS cases, one of whom had weak MMR protein staining. Germline P/LP variants in DNA damage repair genes were found in 11 cases. In addition, we found that 11 patients had high- or moderate- penetrance P/LP mutations other than MMR genes. The common P/LP variants in high- or moderate-penetrance genes were 4 in ATM, 3 in MSH6 and KIT, and 2 in APC, NF1 and DICER.ConclusionsWe identified approximately 11% of UTUC cases as suspected LS and at least 1.4% patients with confirmed LS-associated UTUC. In addition, broader germline genetic testing could be considered to screen for cancer severity in hereditary UTUC patients.

Renal cell carcinoma (RCC) is one of the most common urological cancers. RCC has a poor prognosis and is considered a metabolic disease. It has been reported that many metabolic pathways are associated with the development of RCC. However, the prognostic value of metabolism-related genes in RCC is unclear. We herein aimed to establish a scoring system based on the gene expression profile of metabolic genes to evaluate the response to immunotherapy and predict the prognosis of RCC. In this study, we collected multicentre RCC data and performed integrated analysis to characterize the role of tumour metabolism in RCC and explore the relationship between metabolism and prognosis and immune therapy. Based on transcriptomic data, metabolism-related genes were used for nonnegative matrix factorization clustering. We obtained three subclasses of RCC (M1, M2, and M3), and they are associated with different prognoses and immune infiltrate levels. Then, based on the pathway activity of 113 metabolism-related gene signatures, we classified patients into three distinct metabolism-related signatures. Finally, we provide a metabolism-related pathway score (MRPScore) that is significantly associated with RCC prognosis and the response to immunotherapy. Taken together, in this study, we established an RCC classification system based on metabolic gene expression profiles that could further the understanding of the diversity of RCC. We also present the MRPScore, which may be used as an indicator to predict the response to clinical immune therapy.