Objective:Objectives The aim of the study is to evaluate the mechanical performance, safety and efficacy of the novel robotic-assistant flexible ureteroscopy system (Ra-fURS) under in vitro and in vivo environments.Methods:Combing with commercial flexible ureteroscopes, the novel Ra-fURS was used for the in vitro test and animal model operation in October 2020. The study included three sections. ①Basic mechanical performance assessment: including endoscope motion control (dual deflection, axial rotation and forward/backward distance), reaction time and fiber regulation. ②Simulated surgery in ex-vivo 3D-printing renal collecting system model: including completion rate and time of calyxes exploration, directional movement and laser fragmentation [gypsum models (0.5×0.5×0.5 cm) were used to stimulate kidney stones]. ③Intrarenal surgeries in animal models (two 5-month female Yorkshire white pigs). In total, 32 surgeries was performed (8 surgeons × 2 pigs × 2 kidneys/pig). In vivo assessments were carried out including: ①consuming time for Ra-fURS installation and offloading; ②completion rate and time of calyxes exploration; ③comfort score (ranging from 0-10) as compared to the manual f-URS, which was corresponding to each Ra-fURS surgery. In simulated surgery and animal surgery sections, 8 surgeons were enrolled in the study (group A 4 without flexible ureteroscopy experience; group B: 4 highly experienced), and results were compared between two groups.Results:Under the Ra-fURS control, the flexible ureteroscope movement in three degrees of freedom (forward / backward: + 11 to -11 cm, axial rotation + 225°to -225°; active duel-flection: + 270°to -270°, as well as the laser fiber regulation + 2.5 to -2.5 cm). In simulated surgery tests, both groups achieved 100% completion rate of calyxes exploration, and there were no statistical differences in the time of the calyxes exploration between group A and group B (116.0±8.0)s vs.(110.3±15.4)s( P>0.05). Time-consumption for laser fragmentation of group B was shorter than that of group A (525.8±58.5)s vs. (780.5±141.2)s( P<0.01). In animal surgery, the installation time of Ra-fURS gradually shortened within the first 7 cases was(234.0±43.0)s, and became comparable in the later 8-32 cases was(149.3±8.0)s. The average uninstall time was (43.9 ±5.9)s and was relatively stable. There were 51 renal calyxes in two pigs. It was higher for the completion rate of calyxes exploration in group B than in group A [(95.5±9.1)% vs. (59.1±9.1)%, P<0.05], and the exploration time was also statistically variant between the two groups group A and group B[(274.8±34.6)s vs.(127.3±18.2)s, P<0.05]. For all the operators, the comfort scores were favorable to the Ra-fURS as compared to the manual f-URS (8.9±0.3 vs. 5.9±1.1, P<0.05). Conclusions:This preliminary study demonstrated that the novel Ra-fURS was capable of controlling flexible ureteroscope to perform retrograde intrarenal surgery and fragmenting stones with laser. Besides, other features, including easy installation, stable performance and comfortable manipulating environment, made it easy to use in clinical application.

Objective To study the effect of diffusion-weighted magnetic resonance imaging (DW-MRI) in the differential diagnosis of hydronephrosis and pyonephrosis.Methods From March 2015 to October 2017,50 patients with renal stone and highly suspected infectious hydronephrosis underwent renal DW-MRI,and clinical materials were collected and analyzed retrospectively.Seventeen male and 33 female patients were enrolled with a mean age of (49.40 ±-10.51) years.The median maximum diameter of renal stone was 30.30 (17.38,56.01) mm and hydronephrosis was 46.39 (34.33,56.55) mm.No pyonephrosis was diagnosed by preoperative ultrasound or CT,while 29 cases of hydronephrosis and 21 cases of pyonephrosis were reported by preoperative DW-MRI.Final diagnoses of hydronephrosis and pyonephrosis were made according to whether the pelvic urine drainage was purulent or not during the surgery.DW-MRI reports and characteristics of DW images were analyzed retrospectively.Apparent diffusion coefficient (ADC) was calculated and ADC map constructed,which was compared between the two groups.Receiver operating characteristic curve (ROC) was drawn to analyze the area under curve (AUC) and the optimal cutoff of ADC value,with sensitivity and specificity.Results Thirty-three patients of hydronephrosis and 17 pyonephrosis were confirmed intraoperatively.The overall accuracy of diagnosis using DW-MRI was 84.00％ (42/50),with sensitivity of 88.24％ (15/17) and specificity of 81.82％ (27/33).Among 30 patients who underwent CT scan in our hospital,mean CT value of 18 hydronephrosis was (7.03 ± 3.26)HU and that of 12 pyonephrosis was (8.67 ± 3.52) HU,with no statistical significance (P ＞ 0.05).On DW image,when b ≥ 500 s/mm2,hydronephrosis signal intensity was lowered apparently,whereas pyonephrosis signal intensity was intensified.On ADC map,hydronephrosis appeared as hyperintensity,whereas pyonephrosis appeared as hypointensity.The mean ADC value of pyonephrosis group was lower than hydronephrosis group [(1.53 ±0.58) × 10-3 mm2/s vs.(2.86 ±0.56) × 10-3 mm2/s,p ＜0.01].ROC analysis revealed that AUC =0.92 (95％ CI 0.80-0.98),and the cut-off value of ADC for pyonephrosis diagnosis was 1.39 × 10-3 mm2/s,of which the sensitivity and specificity was 94.12％ and 84.85％ respectively.Conclusions Signal of pyonephrosis was enhanced on DW image,while decreased on ADC image.The ADC value of pyonephrosis was much lower than that of hydronephrosis,with which the differential diagnosis between pyonephrosis and hydronephrosis could be made efficiently.

Objective: To summarize the initial experience of flexible ureteroscopy combined with thulium laser for the treatment of high-risk upper urinary tract urothelial carcinoma (UTUC) in patients with solitary kidney or renal insufficiency. Methods: A retrospective analysis was performed in 5 cases of UTUC with solitary kidney or renal insufficiency treated via flexible ureteroscopy combined with thulium laser from May 2016 to November 2018. Patients consisted of 4 cases of left side tumor, 1 case of right side tumor, with median age of 73 years old(ranging 53-87 years old). Among the 5 cases, 3 were solitary kidney with renal pelvis tumors, 2 cases were renal insufficiency accompanied with proximal ureter or renal pelvis tumor. All the patients had tumors large than 2 cm in diameter. The creatine in 3 cases with solitary kidney was 102, 128, 143μmol/L, respectively. The creatine in 2 cases with renal insufficiency was 281, 179μmol/L, respectively. Variable hydronephrosis was noticed in all paients. The cytological examination could reveal tumor cells in all cases. During the operation, part of tumor tissues were resected for pathological examination and the remaining visible tumor tissue was all ablated and vaporized. As there was no obvious residual tumor tissue, double J stent was retained. Patients were regularly reexamined after surgery. Results: Of the 5 cases, 4 patients were successfully performed, while intraoperative bleeding occurred in 1 case. The operation was suspended after indwelling double J stent. Then, the renal artery interventional embolism was performed after ineffective conservative treatment, and the bleeding was well controlled. One month later, the patient was treated with thulium laser tumor ablation and vaporizaiton under flexible ureteroscopy again. The pathology of all cases was high-grade invasive urinary epithelial carcinoma. Patients were followed up with regular imaging and endoscopic examination. The median follow-up period was 19 (4-26) months, during which 4 cases had local recurrence, one patient died of non-tumor factors. No recurrence of urothelial carcinoma occurred in the bladder during follow-up, the overall recurrence rate was 80%, and the median recurrence time was 6 (1-24) months. Patients with recurrence was treated with thulium laser tumor ablation and vaporizaiton under flexible ureteroscopy again. Conclusions Flexible ureteroscopy combined with thulium laser is an alternative treatment for high-risk upper urinary tract urothelial carcinoma in patients with solitary kidney or renal insufficiency, while with high tumor recurrence rate. Therefore, a stringent imaging and endoscopic follow-up should carry out postoperatively.

Objective:To investigate the role of TcpC, a virulence factor of uropathogenic Escherichia coli (UPEC), in immune evasion, and analyze its related pathogenic mechanism. Methods:C57BL/6 mice were injected with 10 9 colony-forming unit of wild-type (CFT073 wt) or tcpc gene-knockout (CFT073 Δ tcpc) UPEC CFT073 strains from urethra into bladder to construct a mouse model of pyelonephritis. These mice were sacrificed 5 d after infection and their kidneys were taken to observe the gross pathological changes. Hematoxylin-eosin staining was used to observe histopathological changes in kidney tissues and immunohistochemistry was performed to locate TcpC in kidney tissues. The bacterial loads in urine samples of UPEC infected-mice were counted by ten-fold dilution method, and the presence of tcpc gene in the genomic DNA of bacteria from CFT073-infected mouse kidney or urine samples was measured by PCR. The expression of TcpC at mRNA level was detected by qRT-PCR after infecting dendritic cells with CFT073 wt strains. The influences of UPEC infection on the activation of NF-κB signaling pathway and the secretion of proinflammatory factors by dendritic cells were analyzed by Western blot and ELISA, respectively. The viability of UPEC strains in dendritic cells were observed by laser confocal microscope. Results:Compared with the CFT073 Δ tcpc group, the mice in the CFT073 wt group had obvious abscess in the kidneys as well as massive neutrophil infiltration and abundant TcpC in kidney tissues. The bacterial loads in the urine of CFT073 wt-infected mice were significantly higher than those in the urine of CFT073 Δ tcpc mice. PCR results showed that tcpc gene was successfully amplified from mouse kidney and urine samples. Increased expression of TcpC at both mRNA and protein levels was detected in CFT073 wt-infected dendritic cells. CFT073 wt infection inhibited the phosphorylation of NF-κB p50 and the production of proinflammatory factors in dendritic cells. TcpC promoted the survival of CFT073 wt in dendritic cells. Conclusions:TcpC expression increases significantly during CFT073 wt infection or in mice with CFT073 wt-induced pyelonephritis. It promotes the survival of CFT073 wt in dendritic cells by inhibiting the activation of NF-κB signaling pathway and reducing the secretion of pro-inflammatory cytokines. TcpC is involved in the pathogenesis of UPEC and immune evasion.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.