INTRODUCTION: We aimed to compare the real-world data and our clinical experience with metallic stents (MSs) and conventional polymeric stents (PSs) in the management of both malignant and benign chronic ureteric obstruction (CUO), in terms of clinical outcomes and costs. METHODS: Clinical data from our institution, including outcomes for all ureteric stents inserted for long-term management of CUO from all causes from 2014 to 2017, were retrospectively reviewed and compared between the MS and PS episodes. RESULTS: A total of 247 stents were placed in 63 patients with CUO over the 4-year study period. Of these, 45 stents were MSs. There was no significant difference in all baseline characteristics between the MS and PS groups, except for the aetiology of obstructive cause. Mean indwelling stent duration was significantly greater for MS than for PS (228.6 ± 147.0 vs. 146.1 ± 66.0 days, P < 0.001), thereby leading to lower average number of stent changes per year in the MS group compared to the PS group (1.4 vs. 6.3 times, respectively). Despite the higher unit cost of MS compared to PS, there was no significant mean cost difference overall (cost per dwelling day SGD 7.82 ± SGD 10.44 vs. SGD 8.23 ± SGD 20.50, P = 0.888). CONCLUSION Resonance MS is a better option than PS to manage CUO from malignant and benign causes because its significantly longer indwelling time mitigates the higher unit cost of the stent. It potentially reduces the number of procedures and operations in patients. Thus, it should be considered for all patients with CUO requiring long-term ureteric drainage.
Humans ; Ureteral Obstruction/economics* ; Female ; Male ; Retrospective Studies ; Stents/economics* ; Middle Aged ; Aged ; Treatment Outcome ; Chronic Disease ; Ureter/surgery* ; Metals ; Adult ; Aged, 80 and over

Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

Objective： To analyze the symptoms, diagnosis and treatment of upper urinary tract calculi patients combined with mild and moderate benign prostatic hyperplasia (BPH) after ureteral stent implantation. Methods： One hundred and six BPH patients who were hospitalized for upper urinary tract calculi and had ureteral stents retained from January 2019 to December 2022 were selected and divided into 2 weeks group and 4 weeks group according to the time of removal of ureteral stents after surgery. Their general clinical data were analyzed and compared. International Prostatic Symptom Scale (IPSS), postoperative ureteral Stent Symptom Questionnaire (USSQ), and incidence of adverse events after ureteral stent removal were recorded before and after removal. Results： The scores of IPSS were significantly increased in all patients, and symptoms in urinary tract had improved significantly after discharge (P<0.05). Compared with the 2 weeks group, the USSQ score of the 4 weeks group was significantly increased (P<0.05). And no significant adverse event was observed in the 2 weeks group after the removal of ureteral sten. Conclusion： IPSS score and USSQ score increased significantly during stent implantation in BPH patients with lithiasis. And complications increased significantly over time. Following thorough clinical assessment, early ureteral stent removal demonstrates both safety and efficacy, representing an optimal therapeutic approach in selected cases.
Humans ; Male ; Prostatic Hyperplasia/surgery* ; Stents ; Ureter/surgery* ; Aged ; Middle Aged ; Urinary Calculi/surgery* ; Ureteral Calculi/surgery*

OBJECTIVES: To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis. METHODS: Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS: After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.
Mice ; Animals ; Humans ; Transforming Growth Factor beta1/metabolism* ; Diabetic Nephropathies/pathology* ; Transcriptome ; Signal Transduction ; Kidney ; Ureteral Obstruction/pathology* ; Fibrosis ; Interferon Regulatory Factors ; Transforming Growth Factor beta/metabolism* ; DNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism*

Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats ; Mice ; Animals ; Ureteral Obstruction/metabolism* ; Kidney/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Molecular Docking Simulation ; Rats, Sprague-Dawley ; Kidney Diseases/drug therapy* ; Extracellular Matrix/metabolism* ; Flavonoids/metabolism* ; Fibrosis

OBJECTIVE: To explore the impacts of delayed ureteral stent removal on the quality of life (QoL) and mental health of urinary calculi postoperative patients due to the corona virus disease 2019(COVID-19) pandemic. METHODS: The demographic and clinical data of patients with ureteral stent placement after urinary endoscopic lithotripsy and returned to Peking University People's Hospital for stent removal from December 2019 to June 2020 were collected. Ureteral stent symptoms questionnaire (USSQ) score and the outcome 20-item self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were collected to estimate the QoL and mental status. The USSQ consisted of 44 questions in 6 domains (including urinary symptom, physical pain, general health, work performance, sexual function, and ureteral stent related infection). For most questions in each domain, its score was a five-point Likert-type scale from 1 to 5, and a small proportion of questions was quantified by 1 to 4 or 1 to 7 scale. SAS and SDS both contained 20 questions used to assess a patient's level of anxiety and depression. Its scoring for each item was on a four-point Likert-type scale from 1 to 4. A total score (ranging from 20 to 80) was the main statistical indicator. The level of clinical anxiety and depression was quantified by using standard scores (total score multiplied by 1.25 to produce integers). And the multi-group structural equation model was constructed by analysis of moment structure (AMOS) analysis. RESULTS: Overall, 71 patients were enrolled for analysis. It was found that the median duration of ureteral stent time differed significantly between the control and delayed groups for 32 (30, 33) d and 94.5 (88, 103) d, respectively. The delayed group resulted in higher scores in the USSQ multidimensional, which included urinary symptoms, general health, work performance and ureteral stent related infections. Anxiety and depression were also significantly serious in the delayed group than in the control group. A longer indwelling time of a ureteral stent could exacerbate the effects of urinary symptoms and physical pain on work performance (P=0.029 < 0.05). Among them, the patients with severe urinary symptoms leading to poor work performance were most significantly affected by prolonged ureteral stent duration time (CR=2.619>1.96). CONCLUSION Patients with delayed ureteral stent removal due to the COVID-19 had resulted in worse QoL and mental status. Stents related symptoms are more severe in patients with higher anxiety and depression degree during COVID-19. To improve the QoL and mental health of patients after urinary calculi surgery during COVID-19, it is still not recommended to prolong the stent duration time or corresponding intervention measures should be taken.
Humans ; Quality of Life ; Pandemics ; COVID-19/epidemiology* ; Ureter/surgery* ; Urinary Calculi ; Pain ; Ureteral Diseases ; Stents ; Surveys and Questionnaires ; Ureteral Calculi

This paper analyzed the clinical data, diagnosis and treatment of 4 asymptomatic patients with ureteral calculi without hydrops in our hospital from October 2018 to January 2019, and comprehensively discussed the previous literature. The 4 patients in this group had no obvious clinical symptoms, no positive stones were found in the B-ultrasound of the urinary system, and no hydroureter and hydroureter of the affected side was found. Urinary CT scan confirmed ureteral stones. They were all located in the lower ureter, and the stones obstructed the lumen. The stones were round and smooth, and there was no obvious hyperplasia and edema in the surrounding mucosa. The lithotripsy was completed in the first-stage operation, and the DJ catheter was left behind for one month after the operation. Based on the clinical diagnosis and treatment process of the 4 cases of asymptomatic calculi in this group and the analysis of previous studies, these patients were mostly detected by imaging examinations or other systematic imaging examinations during the regular review of urinary calculi. Ureteral stones with obstruction did not necessarily have stone-related symptoms. The onset of renal colic involved an increase in intraluminal pressure, related stimulation of nerve endings, smooth muscle spasms caused by stretching of the ureteral wall, and systemic changes in cytokines and related hormones. Cascade reactions, etc., were associated with the movement of stones down. Ureteral stones without hydrops were mostly located in the lower ureter, which had a certain buffering effect on obstructive pressure. Asymptomatic ureteral calculi could also induce irreversible damage to renal function, and the proportion of damage increased with the diameter of the stone. Patients with a history of urinary calculi, especially those with asymptomatic stones for the first time, should be paid attention to during clinical follow-up. At present, there are few research reports on asymptomatic and non-accumulating ureteral calculi. We analyze the clinical diagnosis and treatment process and characteristics of this group of patients combined with previous literature to provide a reference for the diagnosis and treatment of such patients.
Humans ; Ureteral Calculi/therapy* ; Urinary Calculi/therapy* ; Ureter ; Lithotripsy/methods* ; Edema/therapy* ; Kidney Calculi/therapy*

Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.
Humans ; Urinary Bladder Neoplasms/diagnosis* ; Carcinoma, Transitional Cell/pathology* ; Reproducibility of Results ; DNA Copy Number Variations ; Kidney Neoplasms ; Ureteral Neoplasms ; Sensitivity and Specificity

OBJECTIVE: To compare the safety and effectiveness of active migration technique and in situ lithotripsy technique in the treatment of 1-2 cm upper ureteral calculi by retrograde flexible ureteroscopy. METHODS: A total of 90 patients with 1-2 cm upper ureteral calculi treated in the urology department of Beijing Friendship Hospital from August 2018 to August 2020 were selected as the subjects. The patients were divided into two groups using random number table: 45 patients in group A were treated with in situ lithotripsy and 45 patients in group B were treated with active migration technique. The active migration technique was to reposition the stones in the renal calyces convenient for lithotripsy with the help of body position change, water flow scouring, laser impact or basket displacement, and then conduct laser lithotripsy and stone extraction. The data of the patients before and after operation were collected and statistically analyzed. RESULTS: The age of the patients in group A was (51.6±14.1) years, including 34 males and 11 females. The stone diameter was (1.48±0.24) cm, and the stone density was (897.8±175.9) Hu. The stones were located on the left in 26 cases and on the right in 19 cases. There were 8 cases with no hydronephrosis, 20 cases with grade Ⅰ hydronephrosis, 11 cases with grade Ⅱ hydronephrosis, and 6 cases with grade Ⅲ hydronephrosis. The age of the patients in group B was (51.8±13.7) years, including 30 males and 15 females. The stone diameter was (1.52±0.22) cm, and the stone density was (964.6±214.2) Hu. The stones were located on the left in 22 cases and on the right in 23 cases. There were 10 cases with no hydronephrosis, 23 cases with grade Ⅰ hydronephrosis, 8 cases with grade Ⅱ hydronephrosis, and 4 cases with grade Ⅲ hydronephrosis. There was no significant diffe-rence in general parameters and stone indexes between the two groups. The operation time of group A was (67.1±16.9) min and the lithotripsy time was (38.0±13.2) min. The operation time of group B was (72.2±14.8) min and the lithotripsy time was (40.6±12.6) min. There was no significant difference between the two groups. Four weeks after operation, the stone-free rate in group A was 86.7%, and in group B was 97.8%. There was no significant difference between the two groups. In terms of complications, 25 cases of hematuria, 16 cases of pain, 10 cases of bladder spasm and 4 cases of mild fever occurred in group A. There were 22 cases of hematuria, 13 cases of pain, 12 cases of bladder spasm and 2 cases of mild fever in group B. There was no significant difference between the two groups. CONCLUSION Active migration technique is safe and effective in the treatment of 1-2 cm upper ureteral calculi.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Ureteral Calculi/surgery* ; Hematuria/therapy* ; Ureteroscopy/methods* ; Lithotripsy/methods* ; Lithotripsy, Laser/methods* ; Hydronephrosis/complications* ; Pain ; Treatment Outcome ; Retrospective Studies

Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm³ (range: 85 to 186 cm³). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.
Aged ; Aged, 80 and over ; Humans ; Lithotripsy ; Lithotripsy, Laser ; Male ; Middle Aged ; Prostatic Hyperplasia/complications* ; Retrospective Studies ; Treatment Outcome ; Ureteral Calculi/surgery* ; Ureteroscopy