Background: Oxidative injury to renal epithelial cells promotes calcium oxalate crystal retention, but the upstream regulators linking lithogenic stress to epithelial damage remain incompletely defined.Methods We integrated four public renal transcriptomic datasets with urinary S100A6 measurements in 102 patients with calcium oxalate nephrolithiasis and 106 healthy controls. Cellular gain- and loss-of-function studies, kidney-specific conditional S100A6 deletion, promoter assays, and structure-guided pharmacological experiments were used to define mechanism and therapeutic tractability. Findings: Transcriptomic analyses converged on increased S100A6 and reduced miR-493-5p in calcium oxalate-associated kidney injury. Urinary S100A6 levels were significantly higher in patients with calcium oxalate nephrolithiasis than in healthy controls (median, 66.78 vs 13.49 pg/mL; area under the receiver operating characteristic curve, 0.8821). Oxalate-induced loss of miR-493-5p relieved S100A6 repression, promoting STAT3 phosphorylation and STAT3-dependent transactivation of p67phox and p40phox, with increased reactive oxygen species, autophagic responses, apoptosis, and crystal adhesion. Kidney-specific conditional S100A6 deletion reduced renal crystal deposition and injury. AP-048 bound S100A6 (KD =12.3 μM), attenuated epithelial injury in vitro, and reduced renal crystal deposition in vivo without evident short-term toxicity at the tested dose. Interpretation: S100A6 links lithogenic stress to STAT3–NADPH oxidase-associated oxidative epithelial injury and crystal retention. These findings support urinary S100A6 as a candidate non-invasive biomarker and S100A6 as a tractable target for preventive intervention. Funding Guangdong Basic and Applied Basic Research Foundation: Provincial-Enterprise Joint Fund (2023A1515220222).
This study evaluates the consistency between intrarenal pelvic pressures (IPP) and intracaliceal pressures (ICP) and explores the impacts of irrigation flow rate (IFR) and ureteral access sheath (UAS) position on ICP using a novel Flexible Ureteroscope Pressure Measurement System. Six pigs with 12 kidneys were included in this study under general anesthesia. The IPP and ICP were measured using the Flexible Ureteroscopic Pressure Measurement System under varying UAS positions and IFRs. The 12/14Fr UAS was sequentially placed in the upper, middle, and lower segments of the porcine ureters. The irrigation pump was set to cumulative flow rates of 20, 30, 40, and 50 mL/min. Hemodynamic parameters were monitored using the Edwards Lifesciences monitoring system. The experiment was successfully completed in 10 kidneys. One kidney failed due to issues with UAS placement, and another was penetrated by the UAS. No significant difference was observed between the middle calyx ICP and IPP. ICP in the upper and lower calyces was higher than IPP, with the discrepancy being minor at 20 or 30 mL/min IFR but significant at higher IFRs of 40 and 50 mL/min. The ICP increased with higher IFRs and when the UAS was set in the low ureteral segment. Under the same IFR and UAS position, ICP varied among the three calyces (lower calyx > upper calyx > middle calyx). The Edwards Lifesciences monitoring system accurately measured hemodynamic parameters, which remained stable even at an IFR of 50 mL/min. The Flexible Ureteroscopic Pressure Measurement System can be used to measure the IPP and ICP. These pressures were not consistent across different IFRs and UAS positions. The highest ICP was observed in the lower calyx.
Dissolving the lipid droplets in tissue section with alcohol during a hematoxylin and eosin (H&E) stain causes the tumor cells to appear like clear soap bubbles under a microscope, which is a key pathological feature of clear cell renal cell carcinoma (ccRCC). Mitochondrial dynamics have been reported to be closely associated with lipid metabolism and tumor development. However, the relationship between mitochondrial dynamics and lipid metabolism reprogramming in ccRCC remains to be further explored. We conducted bioinformatics analysis to identify key genes regulating mitochondrial dynamics differentially expressed between tumor and normal tissues and immunohistochemistry and Western blot to confirm. After the target was identified, we created stable ccRCC cell lines to test the impact of the target gene on mitochondrial morphology, tumorigenesis in culture cells and xenograft models, and profiles of lipid metabolism. It was found that mitofusin 2 (MFN2) was downregulated in ccRCC tissues and associated with poor prognosis in patients with ccRCC. MFN2 suppressed mitochondrial fragmentation, proliferation, migration, and invasion of ccRCC cells and growth of xenograft tumors. Furthermore, MFN2 impacted lipid metabolism and reduced the accumulation of lipid droplets in ccRCC cells. MFN2 suppressed disease progression and improved prognosis for patients with ccRCC possibly by interrupting cellular lipid metabolism and reducing accumulation of lipid droplets.
Ureteral stricture is a common urological condition caused by the proliferation of scar tissue at the site of the stenosis. Effectively inhibition of scar tissue proliferation at ureter is key to preventing stenosis after ureteral injury. Retention of an anti-fibrotic-loaded ureteral stent tube that gradually releases the drug can inhibit scar tissue proliferation, thus preventing and treating ureteral stricture. In this study, double layers drug release system was used to carry pirfenidone to create ureteral stent tubes for preventing ureteral stricture. Long-term sustained release of pirfenidone was assessed, and the anti-stenosis drug was continuously released by the stent, which also provided drainage support. Drug release data showed that the stent tube experiments rapidly released pirfenidone over the first 5 days, with the release becoming stable and gradual over the subsequent 9 days. In vitro data showed that the stent tube had a sustained inhibitory effect on human ureteral smooth muscle cells, a significant inhibitory effect on macrophages and an anti-inflammatory factor release effect. More importantly, in vivo data showed that the stent tube had a significant inhibitory effect on ureteral stricture formation in a model of porcine ureteral stricture. These results suggested that the proposed stent tube, a novel pirfenidone sustained-release stent, can effectively inhibit the formation and progression of ureteral stenosis in vitro and in vivo.
The recurrence and metastasis of renal cell carcinoma ar e severe challenges in clinical treatment. At present, it is urgent to find a strategy to solve this problem and improve the therapeutic effect. In this study, we designed a programmed release system of anticancer drugs by preparing a nanofiber system with two kinds of diameters and biomaterials (polylactic acid-glycolic acid (PLGA) and silk protein) as drug carriers (paclitaxel), which inspired the occurrence and pathological microenvironment of renal cell carcinoma. The controlled degradation of PLGA nanofibers as a drug carrier achieved the short-term release of paclitaxel, which could rapidly inhibit the spread and metastasis of renal cancer, while the silk protein nanofibers as a drug carrier with slow degradation could provide the long time and continuous release of paclitaxel to prevent the proliferation of renal cancer cells and inhibit recurrence. The synergistic effect of the sustained release system of paclitaxel successfully achieved inhibition of the recurrence and metastasis of renal cell carcinoma and improve the therapeutic effect of renal cell carcinoma. The paclitaxel release profile showed that the PLGA nanofiber drug system provided controlled release of paclitaxel in the first 14 days, while the silk protein nanofiber system provided a relatively stable and long-duration release of paclitaxel (1 month). In vitro experiments showed that the sustained release system of paclitaxel had a lasting inhibitory effect on the proliferation of renal clear cell carcinoma cells. These results indicated that the sustained release system of paclitaxel could be used as a promising drug delivery system with highly efficient implementations to reduce the frequency of systemic administration and inhibit tumor growth and recurrence, which could provide a new strategy for the clinical applications in renal cell carcinoma microenvironment.
Objective:To summarize the clinical experiences in diagnosis and treatment of upper urinary tract stones in patients with hematologic malignancies.Methods:The clinical data of 13 patients with upper urinary tract stones and hematologic malignancies from August 2016 to December 2020 were retrospectively analyzed.Results:All the 13 patients were operated successfully without serious complications. There were 2 cases of upper urinary tract stones with diffuse large B cell lymphoma, 5 cases of chronic lymphocytic leukemia, 1 case of non-Hodgkin lymphoma, 2 cases of chronic lymphocytic leukemia and 3 cases of mixed cellularity Hodgkin's lymphoma. Among them, 8 patients had back pain, fever, and lower urinary tract symptoms as the first symptoms, and 5 patients had upper urinary tract stones detected during hospitalization with hematologic malignancies. 7 patients were removed upper urinary tract stones with retrograde intrarenal surgery, 3 patients underwent percutaneous nephrolithotomy, and 3 patients underwent ureteral stent placement (1 case of chronic lymphocytic leukemia, 2 cases of mixed cellularity Hodgkin's lymphoma). The postoperative follow-up period was 8-16 months (average 12.5 months). 3 patients with ureteral stent placement were returned to the hospital one year after surgery for replacement of the stent. The remaining patients showed no signs of stone recurrence or worsening symptoms.Conclusions:The treatment of upper urinary tract stones in patients with hematologic malignancies is more difficult. It is necessary to combine the clinical characteristics of various hematologic malignancies and perioperative risks for specific evaluation. Intervention is necessary to ensure the safety of the operation and achieve the optimal diagnosis and treatment effect.
输尿管阴道瘘是输尿管损伤后的一种严重并发症,大多数为妇产科手术造成[1,2] ,目前多采用输尿管镜植入双 J 管或开放手术修复输尿管阴道瘘治疗[3].留置双J 管瘘口自愈率低( 5% ~15%) ,开放手术修复输尿管阴道瘘创伤大,患者难以接受[3].近年来,新型覆膜金属支架已应用在输尿管狭窄的治疗中,这类支架具有覆膜结构以及自膨胀金属局段支撑的特点[4~6].2018年11月~2019年6月我们对6例妇科手术致输尿管阴道瘘采用新型覆膜金属支架( Allium Medical)治疗,现报道如下.
Background Bladder paraganglioma (BPG) is one of the rare neuroendocrine neoplasms that develops from neural crest cells. It categorizes into functional and non-functional types based on the catecholamines secretion. Currently, functional BPG is predicted in advance based on signs and symptoms of catecholamine excess, such as hypertension and “micturition attacks”. However, it is often overlooked because of its rareness. Misdiagnosis of a functional tumor may increase the risk of surgical intervention. Case Presentation We reported 3 cases of BPG that they were admitted to the hospital due to abdominal pain or gross hematuria. Computed tomography (CT) scans showed space-occupying lesions in the bladders with diameters less than 3cm. There were no typical catecholamine excess symptoms before surgical intervention. Postoperative pathology confirmed BPG after removal of the tumor. We also analyze 69 cases of BPG that has been reported and found that 78.0% cases were functional among the tumors larger than 3cm. Conclusion Bladder tumors larger than 3cm in diameter can serve as an additional predictor of functional BPG. Patients who are suspected should undergo magnetic resonance imaging (MRI) scans, 123/131 metaiodobenzylguanidine (MIBG) scan, and have their catecholamine levels tested. Once the diagnosis is confirmed, patients should be started on fluid replacement therapy and adrenergic blockade to abate the disorders associated with catecholamine excess.
Double-stranded RNA-specific adenosine deaminase (ADAR1) is a member of the adenosine deaminases acting on RNA family that catalyze the adenosine-to-inosine editing of double-stranded RNA substrates. Several studies have reported that ADAR1 is closely associated with numerous malignancies. However, the functional roles of ADAR1 in prostate cancer (PCa) have not been fully elucidated. Thus, the present study aimed to investigate the effects of ADAR1 on PCa. The results demonstrated that ADAR1 was highly expressed in PCa tissues compared with normal tissues. Furthermore, the protein expression level of ADAR1 was significantly increased in castration-resistant PCa (CRPCa) tissues and CRPCa cell lines. Thus, these findings indicated that ADAR1 may act as a tumor promoter for PCa development. Next, the potential effects of ADAR1-knockdown on the proliferation of DU145 and PC3 cells were investigated. ADAR1 was knocked down via small interfering RNA transfection, which was found to exert antitumor effects on DU145 and PC3 cells at 24 and 48 h post transfection. Furthermore, a significant positive association was observed between ADAR1-knockdown and the apoptosis of DU145 and PC3 cells, which increased the phosphorylation of H2A.X variant histone. The results of the present study indicated a positive association between ADAR1 expression and PCa, which may promote the development of CRPCa. Moreover, ADAR1-knockdown may serve as a tumor suppressor and represent a potential target for the treatment of PCa.
Clear cell renal cell carcinoma (ccRCC) carrying wild-type Von Hippel–Lindau (VHL) tumor suppressor are more invasive and of high morbidity. Concurrently, competing endogenous RNA (ceRNA) network has been suggested to play an important role in ccRCC malignancy. In order to understand why the patients carrying wild-type VHL gene have high degrees of invasion and morbidity, we applied bioinformatics approaches to identify 861 differentially expressed RNAs (DE-RNAs) between patients carrying wild-type and patients carrying mutant VHL from The Cancer Genome Atlas (TCGA) database, established a ceRNA network including 122 RNAs, and elected six survival-related DE-RNAs including Linc00942, Linc00858, RP13_392I16.1, hsa-miR-182-5p, hsa-miR-183-5p, and PAX3. Examining clinical samples from our hospital revealed that patients carrying wild-type VHL had significantly higher levels of all six RNAs than those carrying mutant VHL. Patients carrying wild-type VHL had significantly higher risk scores, which were calculated based on expression levels of all six RNAs, than those carrying mutant VHL. Patients with higher risk scores had significantly shorter survival times than those with lower risk scores. Therefore, the risk scores serve well to predict malignancy and prognosis.
目的 评估新型覆膜金属支架用于移植肾输尿管狭窄的安全性和有效性.方法 回顾性分析2018年12月~2019年10月使用覆膜金属支架治疗的7例移植肾输尿管狭窄的临床资料.结果 7例输尿管狭窄均位于移植肾输尿管膀胱连接部,狭窄段长5~15 mm,平均10 mm,均成功植入覆膜金属支架.6例术前、术后肾功能均正常;1例术前血肌酐455μmol/L,术后3天降至178μmol/L.7例术后3个月复查利尿肾图及尿路造影,提示上尿路引流通畅.随访3~11(6.6±2.6)月.1例术后3个月输尿管狭窄消失,覆膜金属支架排至膀胱,使用输尿管镜经尿道取出.7例均未发生尿路感染、结石形成、下腹痛等.结论 覆膜金属支架治疗移植肾输尿管狭窄安全有效.
Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors in the urinary system. Surgical intervention is the preferred treatment for ccRCC, but targeted biological therapy is required for postoperative recurrent or metastatic ccRCC. Autophagy is an intracellular degradation system for misfolded/aggregated proteins and dysfunctional organelles. Defective autophagy is associated with many diseases. Mul1 is a mitochondrion-associated E3 ubiquitin ligase and involved in the regulation of divergent pathophysiological processes such as mitochondrial dynamics, and thus affects the development of various diseases including cancers. Whether Mul1 regulates ccRCC development and what is the mechanism remain unclear. Histochemical staining and immunoblotting were used to analyze the levels of Mul1 protein in human renal tissues. Statistical analysis of information associated with tissue microarray and The Cancer Genome Atlas (TCGA) database was conducted to show the relationship between Mul1 expression and clinical features and survival of ccRCC patients. Impact of Mul1 on rates of cell growth and migration and autophagy flux were tested in cultured cancer cells. Herein we show that Mul1 promoted autophagy flux to facilitate the degradation of P62-associated protein aggresomes and adipose differentiation-related protein (ADFP)-associated lipid droplets and suppressed the growth and migration of ccRCC cells. Levels of Mul1 protein and mRNA were significantly reduced so that autophagy flux was likely blocked in ccRCC tissues, which is potentially correlated with enhancement of malignancy of ccRCC and impairment of patient survival. Therefore, Mul1 may promote autophagy to suppress the development of ccRCC.
This study assesses the feasibility and effectiveness of using a three-dimensional (3D) printing model for preoperative planning in the treatment of full staghorn stones, specifically in the selection of the most optimal calyx for puncture. Twelve patients were enrolled in this trial. A preoperative CT taken in prone position was performed on each of the patients. 3D models were reconstructed using digital imaging and 3D printers. Three identical models were printed for each patient. Three puncture sites from the upper-, middle-, and lower-pole calyces of the kidney models were selected for simulation of percutaneous nephrolithotomy. The stone-free rates were recorded after each of the simulations. The puncture site that yielded the maximum SFR was translated to the patient for the actual procedure. CT was performed postoperatively on both patients and simulation models. The SFR of patients and simulation models was compared. Correlation analysis and consistency analysis suggested that there was a high degree of consistency between patients and 3D-printed models. The Pearson product-moment correlation coefficient r for the postoperative stone volume of the patients (PoSVP) and postoperative stone volume of the models (PoSVM) was 0.972 (P < 0.001, 95% CI = 0.900–0.992). The Bland–Altman plot of PoSVP to PoSVM showed an icon of 95% consistency 205.8(− 725.5 ~ 1137.1), and 100% of the points were within the 95% limits of agreement. 3D-printed models can potentially be used for preoperative planning in the treatment of full staghorn stones, especially in the selection of the most optimal calyx for puncture.
通过手术视频直播系统, 建立内镜下解剖结构的教学病例库, 模拟还原病例内镜下的解剖结构, 加强学生对疾病诊疗的印象;通过教师引导学生对泌尿系解剖结构研讨, 提高学生对泌尿系解剖结构的认识, 探索内镜下解剖结构教学在泌尿外科临床教学中的应用.采用内镜下解剖结构教学病例库结合以问题为基础的教学法, 学生对泌尿外科临床知识掌握更好, 临床诊疗能力获得提高.该教学方法可以提高教学质量, 值得在泌尿外科临床教学中进一步推广.
Objective To compare the efficacy and safety of percutaneous nephrolithotomy (PCNL) with or without concurrent aspiration in the treatment of renal calculus. Methods We systematically searched PubMed, EMBASE, the Cochrane Controlled Trial Register of Controlled Trials, CNKI, Wanfang, and Chinese Biological Medical Database for randomized controlled trials comparing PCNL with or without aspiration in adult patients with renal calculus. Study quality was assessed by the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was performed by Reviewer Manager Software, Version 5.3. Results Twelve trials with 1 100 patients met the inclusion criteria and were entered into the final analysis. Our pooled analysis showed that PCNL with concurrent aspiration could reduce surgical duration [MD=-10.03; 95%CI(-15.79, -4.27), P=0.0006], postoperative fever [RR=0.41, 95%CI(0.27, 0.61), P<0.001], hemorrhage [MD=-71.63, 95%CI(-136.89, -6.37), P=0.03], Total clavien complication rate [RR=0.54; 95%CI(0.41, 0.71); P<0.001], Clavien Grade II complication rate [RR=0.43, 95%CI(0.30, 0.60), P<0.001], and renal pelvic pressure [MD=-10.47, 95%CI(-11. 49, -9.45), P<0.001]. It could also enhance the stone-free rate [RR=1.11, 95%CI(1.00, 1.23), P=0.05]. However, there was no difference with respect to septic shock [RR=0.43, 95%CI(0.12, 1.63), P=0.22], Clavien Grade I complications [RR=0.83, 95%CI(0.47, 1.48), P=0.53] and Clavien Grade III and above complications [RR=1.12, 95%CI (0.40, 3.15), P=0.83]. Conclusions Compared to PCNL without suction, this meta-analysis shows that PCNL with concurrent aspiration results in a significantly higher stone-free rate and a decrease in surgical duration, fever occurrence, hemorrhage, Clavien total complications, Clavien Grade II complications, and renal pelvic pressure, without an increase in the incidence of septic shock, Clavien Grade I, III and above complications. Key words: Renal calculus; Percutaneous nephrolithotomy; Aspiration; Meta-analysis
Objective To compare the efficacy and safety of preoperative reserved double J catheter and balloon dilatation in the application of retrograde intra-renal surgery (RIRS). Methods Clinical data of 125 patients undergoing RIRS for unilateral ureteral dilatation in our hospital from May 2016 to May 2018 were retrospectively analyzed. Among them, 57 patients received reserved double J catheter for passive ureteral dilatation and 68 cases underwent primary balloon for active ureteral dilatation. General data and postoperative data were statistically analyzed between two groups. Results No statistical difference was observed in gender, age, stone site, the maximum diameter of stones and the number of multiple stones between the two groups (allP>0.05). The proportion of retained 16 F ureteral access sheath (UAS) in the reserved double J catheter group was significantly higher than that in the balloon dilation group (70.2% vs 30.9%,P 0.05). Conclusion Reserved double J catheter and balloon dilatation are safe and effective in RIRS. The selection of ureteral dilatation approach depends on the physical conditions of patients, the expertise of physicians and hospital equipment,etc. Key words: Flexible ureteroscope; Stone; Double J catheter; Balloon dilation; Ureteral access sheath
Objective To systematically analyze the clinical efficacy and safety of micro-percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in the treatment of kidney stones that measure smaller than 3 cm. Methods Through searching PubMed, Cochrane library, Embase, CNKI, Wanfang database and SinoMed, clinical trials related to micro-PCNL and RIRS in treating small-and medium-size kidney stones in both Chinese and English from January 1, 2011 to March 1, 2017 were retrieved. According to the inclusion and exclusion criteria, relevant clinical trial data were extracted from the literatures and statistically analyzed by Revman 5.0 software to draw a conclusion. Results Four articles consisting of 328 patients were included in this meta-analysis, including two randomized controlled trials and two retrospective trials. No statistical significance was noted in terms of the length of hospital stay [(WMD=2.71, 95%CI (-3.78,9.20)], operation time (WMD=6.56, 95%CI (-22.94,36.05)] and postoperative complications [OR=0.99, 95%CI (0.51,1.95)] between RIRS and micro-PCNL, whereas the removal rate of kidney stones by micro-PCNL was significantly higher compared with that by RIRS (OR=2.30, 95%CI (1.24,4.26)]. Conclusion Both micro-PCNL and RIRS are efficacious and safe in the treatment of kidney stones, whereas the removal rate of micro-PCNL is considerably higher than that by RIRS. Key words: Micro, percutaneous nephrolithotomy; Flexible ureteroscope; Kidney stone; Meta-analysis
There are lots of methods in the treatment of caliceal diverticular calculi.Comparing with open sur-gery,the advantage of minimally invasive treatment is more prominent.Minimally invasive treatment can be listed as ESWL,PCNL,RIRS and Laparoscopic surgery.Selecting the best treatment modality represents a controver-sial area in urology,because each treatment method hasits own advantages and disadvantages.The present review summarized the new progress in the minimally invasive treatment of caliceal diverticular calculi.
自 20 世纪 90 年代以来,治疗输尿管疾病的方法从开放手术往微创方向取得了极大的进展,体外冲击波碎石术(extracorporeal shock wave lithotripsy,ESWL)、经尿道输尿管镜气压弹道 / 钬激光技术、输尿管软镜钬激光技术、腹腔镜微创技术等新技术的出现,使许多上尿路疾病患者免除了开放治疗的痛苦 [1].但是,技术更新的同时也带来了一些相应的并发症,例如医源性输尿管狭窄.
目的 探讨经尿道等离子双极前列腺剜除术(PKEP)与经尿道等离子双极前列腺电切术(PKRP)治疗体积>60 mL良性前列腺增生(BPH)的安全性与有效性.方法 检索国内外各大常用数据库中比较PKEP与PKRP治疗体积>60 mL BPH的随机对照研究(RCT),检索日期为2012年1月1日至2017年3月2日,按照纳入排除标准进行文献筛选和数据提取,并进行文献质量评价,使用RevMan 5.3软件进行Meta分析.结果 与PKRP相比,PKEP的前列腺切除质量较多{WMD=15.29,95%CI(9.18,21.40),P<0.001},手术时间较短{WMD=-17.44,95%CI(-28.69,-6.19),P=0.002},留置导尿管时间较短{WMD=-26.51,95%CI(-36.49,-16.54),P<0.001},术中出血量较少{WMD=-77.82,95%CI(-120.90,-34.74),P<0.001},住院天数较少及术后最大尿流率较大,但后两者敏感性较低.PKEP与PKRP术后并发症发生率无统计学差异.结论 比较PKEP与PKRP治疗体积>60 mL BPH,PKEP切除前列腺增生腺体更完全,所需手术时间短,留置导尿管时间较短,术中出血量少,较PKRP安全有效,但由于原始研究质量较低,后期仍需大量高质量、大样本RCT验证后方可进一步临床推广.