Calcium oxalate stones are the most common type of kidney stones in China. The injury and death of renal tubular epithelial cells induced by hyperoxaluria or calcium oxalate crystals are the key factors in the formation of calcium oxalate stones. Renal tubular epithelial cell death can provide attachment sites for calcium oxalate crystals, being part of the composition of stones and aggravate tissue damage. Multiple cell programmed death patterns can participate in cell injury and regulate the intersection to achieve multi-level regulation. This article summarized and discussed the relationship between renal tubular epithelial cell programmed death and the mechanism of calcium oxalate stone formation, and the related research of different programmed cell death patterns involved in the pathogenesis of calcium oxalate stones in recent years.

Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.

Objective:To evaluate the clinical value of nanopore targeted sequencing (NTS) in pathogens detection in urinary tract by comparing the results of different tests performed on the same urine sample.Methods:The results of NTS and urine culture test collected from 326 patients in the Department of Urology of People's Hospital of Wuhan University from July 2020 to June 2021 were retrospectively analyzed. There were 224 males and 102 females. The average age was (56.88 ± 14.58)years old. χ 2 test and Student’s test and Wilcoxon's sign rank test were used to analyze the differences of the pathogen detection rate, pathogen types results and detection time consuming between NTS and urine culture. The clinical value of the NTS in rapid detection of urinary pathogens was evaluated. Results:Among 326 hospitalized patients, the urinary tract microbes’ detecting rate of NTS was significantly higher than that of urine culture[67.80%(221/326)vs. 23.93%(78/326), χ2=130.25, P<0.01]. The uropathogens detecting rate of NTS was significantly higher than that of urine culture[54.29%(177/326)vs. 23.31%(76/326), χ2=38.95, P<0.01]. The number of urinary tract microbes detected by NTS was significantly higher than that of urine culture ( Z=11.49, P<0.01), the number of uropathogens was significantly higher than that of urine culture ( Z=9.67, P<0.01). The detection time of NTS and urine culture positive samples was (24.29±2.65) h and (49.28±11.30) h, the difference was statistically significant ( t =39.48, P<0.01). The results obtained by using NTS and urine culture were consistent in 135 (41.41%) samples. In 150 (46.01%) samples, NTS could detect the urinary tract microbes while urine culture cannot find, of which 112 cases (34.36%) were uropathogenic. In 27 cases (8.28%), more pathogens were detected by NTS except those from urine culture. In 6 cases (1.84%) re-detecting NTS after antibiotic therapy, the number of reads of primary uropathogen decreased gradually with the growth of colonizing bacteria or opportunistic pathogens appeared in the end. Re-examinations of urine culture could verify the results of NTS detection on admission in 5 cases (1.53%). NTS in 2 cases (0.61%) could cover the uropathogens of subsequent several urine cultures. Conclusions:NTS has the advantages of rapid, sensitive and comprehensive detection of urinary tract infection pathogens. When urine culture is not yet reported or even negative, NTS already has a certain clinical reference value and can be used as an effective supplement to urine culture, which is conducive to the comprehensive judgment of the patient's condition.

Objective:To compare the performance and surgical outcomes of domestic single-use digital flexible ureteroscopes with reusable digital flexible ureteroscopes in treatment of upper urinary stones.Methods:A prospective, single-blind, multicenter and randomized controlled study was performed from September 2018 to June 2019. Eligible patients were randomly assigned, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-75 years, solitary upper urinary stone with stone size between 0.8 and 2.0 cm and CT value less than 1 400 HU, negative preoperative urine culture and normal renal function. Exclusion criteria included: patients with acute urinary tract infection, intransitable urethral strictures, impassable ureteropelvic junction obstructions, systemic hemorrhagic disease, coagulation function abnormalities or bleeding tendency, severe hypertension or cardiopulmonary insufficiency, severe hip malformation and difficulty in meeting the demand of operation position and pregnant and lactation women. The device used in the experimental group was a domestic single-use digital flexible ureteroscope, and the device used in the control group was an imported Olympus digital flexible ureteroscope. The qualified rate of clinical comprehensive evaluation (including image quality and operational performance), the rate of device failure, the stone-free rate and the occurrence rate of adverse events (including increase in urine red blood cell and white blood cell counts, postoperative hematuria, nausea, vomiting, dizziness, and fever) in the two groups were recorded.Results:A total of 186 eligible study cases were collected from the People's Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University, and the First Affiliated Hospital of Guangzhou Medical University. 90 cases in the final experimental group and 88 cases in the control group completed the trial and were included in the evaluation. There were no statistically significant differences among age [(48.40±11.36) vs. (47.40±12.53)years old, P=0.594], male to female ratio (62/28 vs. 56/32, P =0.874), BMI [(24.8±2.1) kg/m 2 vs. (25.1±2.0)kg/m 2,P =0.331], hydronephrosis (no/slight vs. mild/severe) (62/28 vs. 65/23, P =0.874), stone location and stone size [(12.8±4.7) mm vs. (11.9±5.2) mm, P =0.227]. There were no significant differences in terms of qualified rate of clinical comprehensive evaluation [98.9% (89/90) vs. 100.0% (88/88), P =0.991], lithotripsy success rate [84.4% (76/90) vs. 84.1% (74/88), P =0.888], device failure/defect rate (both 0%), and the incidence of adverse events [50.0% (45/90) vs. 52.0% (51/88), P =0.894]. The highest incidence of adverse events in two groups was the increase of red blood cells and white blood cells of routine urine after operation. There was no serious adverse event in the experimental group and 1 serious adverse event in the control group. Conclusions:There was no significant difference in image quality, device failure/defect rate, lithotripsy success rate, and adverse event rate between single-use digital flexible ureteroscopes and reusable digital flexible ureteroscopes for lithotripsy of upper ureteral and pelvic stones. Domestic single-use digital flexible ureteroscopes have good safety and effectiveness in the treatment and microscopy of upper urinary tract stones.

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Objective:To explore optimum surgical treatment of ureteral strictures after ureteroscopic holmium laser lithotripsy.Methods:The clinical data of 113 patients with ureteral stricture after ureteroscopic holmium laser lithotripsy from December 2014 to December 2019 were analyzed retrospectively. Of all the patients, there were 73 males and 40 females(aged from 31 to 68) with the mean age of 49 years. The mean length of ureteral stricture was 15mm (from 5mm to 25mm). The mean time since the last holmium laser lithotripsy was 6 months (from 3months to 10 months). According to the different treatment of stenosis, 113 patients were divided into endourological treatment group (34 patients) and reconstruction group(79 patients). According to the different surgical methods, endourological treatment group was divided into ureteral balloon dilatation (18 patients) and ureterotomy (16 patients). Reconstruction group was divided into laparoscopic surgery and open surgery, whose were ureteral stenosis resection and anastomosis. Patients were followed up closely postoperatively. Therapeutic success was defined as disappeared hydronephrosis, and unobstructed anastomosis. Success rate, operation time, postoperative changes of hemoglobin, hospital stay and the incidence of postoperative complications were measured.Results:The follow-up time ranged from 5 months to 53 months, with a median time of 18 months. There was no significant difference in age, sex, BMI, location of ureteral stricture, side of stricture and degree of hydronephrosis between endourological treatment group and reconstruction group( P>0.05). The length of ureteral stricture in reconstruction group was significantly longer than that in endourological treatment group (10.3±4.2 mm vs. 17.2±7.8mm, P<0.001). Although the operation time, postoperative changes of hemoglobin, hospital stay and the incidence of postoperative complications were lower in the endourological treatment group compared to reconstruction group ( P<0.001), the overall success rate of the reconstruction operation was significantly higher than that in endourological treatment group (96.2% vs. 61.8%, P<0.001). Furthermore, there was no significant difference in the success rate between laparoscopic surgery group and open surgery group (95.3% vs.97.2%, P<0.05), and there was no significant difference between the balloon dilatation group and the stenosis internal ureterotomy group (66.7% vs.56.3%, P<0.05).113 cases were followed up for an average of 18 (5-53) months. Conclusions:For the treatment of ureteral stricture after ureteroscopic holmium laser lithotripsy, the success rate of reconstruction group (laparoscopic surgery and open surgery)was significantly higher than that of endourological surgery (balloon dilatation and internal ureterotomy). Reconstruction surgery is the optimum surgical treatment to treat ureteral stricture after ureteroscopic holmium laser lithotripsy.

Objective: To investigate the value of diagnostic digital flexible ureteroscopy in patient with hematuria from unilateral upper urinary tract. Methods: A retrospective analysis was made in consecutive 140 cases, including 94 males and 46 females, who are considered for hematuria from unilateral upper urinary tract in Renmin hospital of Wuhan University from January 2014 to February 2019.Their age ranged from 22 to 89 years, with mean of 62.3 years. The mean BMI was 24.6 kg/m²(ranging 22.1-28.2 kg/m²). All patients complained about the continuously or intermittently gross hematuria. 29 cases (20.7%) complained about the flank pain, as well. All cases were examined by urinary sonography, CTU and voided urine cytology preoperatively. Occupying lesion was found in 47 case by sonography including suspected diagnosis. Upper tract urothelial carcinoma(UTUC) was diagnosed in 63 cases by CTU including suspected diagnosis.Voided cytology was positive in 17 cases. Concomitant bladder or urethral lesions were excluded by cystoscopy. Hematuria was confirmed from left side in 82 cases(58.6%) and from right side in 58 cases(41.4%). Diagnostic digital flexible ureteroscopy were performed under general anethesia strictly according to 'No touch technique’. Biopsy for suspicious lesions as well as selective in situ cytology were acquired during ureteroscopy. Results: All patients accepted the examination successfully. The duration of follow-up ranged from 3 to 37 months, with mean of 13 month. Benign lesions were found in 71 cases(50.7%) while malignant lesions were identified in 69 cases(49.3%). Benign lesions included 39(54.9%)minute venous rupture, 12 (16.9%)hemangioma, 3 (4.2%)varix and 11 (15.5%)no obvious lesion. The overall success rate of ureteroscopic treatment was 66(93.0%) whereas recurrence rate after treatment was 8(11.3%). Malignant lesions including 67(97.1%) cases with UTUC and 2 cases with squamous carcinoma. The radical nephroureterectomy(RNU)and bladder sleeve resection was performed in all cases. To 67 cases with UTUC, the overall identification rate of urinary sonography, CTU, voided urine cytology, selective in situ cytology and diagnostic digital flexible ureteroscopy was 41(61.2%), 61(91.0%), 13(19.4%), 38(56.7%) and 63(94.0%) respectively. Identification rate of selective in situ cytology was superior to voided cytology(P<0.01) while diagnostic digital flexible ureteroscopy was no significant difference compared with CTU. The concordance of pathological grade between biopsy and final resection specimen was 73.1%.The concordance of low grade was 93.3% whereas high grade was 56.8%. Up-grading was found in 16(23.9%) cases while down-grading was found in 2(3.0%) cases. Intravesical recurrence was affirmed in 11(16.4%) cases during follow-up. Conclusions Diagnostic digital flexible ureteroscopy may not only present qualitative as well as localized evidence for etiological diagnosis of hematuria from unilateral upper urinary tract, but also provides strategy choice for treatment.

Objective A retrospective study was conducted to investigate the clinical epidemiology of ufinary calculus in Hubei province to provide the population characteristics,stone distribution characteristics,treatment methods,surgical costs and other clinical epidemiological data of patients with trinary calculus,and to provide clinical evidence for the development of prevention and treatment measures for urinary calculi.Methods According to the geographical position,local tertiary hospitals were selected as survey objects and medical records such as age,sex,occupation,stone position,type of operation,and cost of surgical treatment of urinary stone disease were retrospectively investigated between January,2015 and December,2017.Result A total of 193 784 patients were enrolled in this study from 27 hospitals in Hubei province.In which,76 209 were admitted to the hospital for urinary calculus,accounting for 39.33％.Among them,49 460 patients were males (64.90％) and 26 749 were females(35.10％),which the ratio was 1.85∶ 1.All age groups can suffer from urinary calculus,with the peak age range from 41 to 70 years old with 58 985 cases,accounting for 77.40％.The main proportion of patients with urinary calculus were farmers with 21 818 cases (28.63％),comparing with workers (9.74％),busioess man (5.58％),government employees (5.14％),retirees (11.25％) and unemployed (12.58％).A total of 71 439 patients with upper urinary calculus and 4 770 patients with lower urinary calculus and the ratio of upper and lower urinary calculus was 14.98∶ 1.From 2015 to 2017,23 567 patients with urinary calculi underwent ureteroscopic]ithotripsy,and 14 681 patients underwent percutaneous nephrolithotomy.The average operation cost of patients with urolithiasis was 18 395.52 RMB,18 566.31 RMB,19 080.91 RMB in 2015,2016,2017 respectively.Conclusion Hubei province is an area with high incidence of urinary calculus,accounting for 39.33％.The high incidence age is 41-70 years.The occupation composition is mainly farmers.In the past three years,the cost of surgery gradually increased.

Objective To evaluate the safety and efficacy of ultrasound guided flexible ureteroscopic lithotripsy.Methods From January 2015 to December 2016,a randomized clinical trial enlisted 130 patients,presenting symptomatic renal stones with 1.3-2.0 cm,in our center.Patients were randomly assigned to ultrasound or radical guided retrograde intrarenal surgery (RIRS) with flexible ureteroscope.There were 37 male and 28 female patients in ultrasound group.Their mean age,BMI index and stone size were (47.7 ± 21.3) years,(22.1 ± 4.7) kg/m2 and (1.4 ± 0.2) cm,respectively.In radical group,there were 22 male and 43 female patients.Their mean age,BMI index and stone size were (51.3 ± 19.2) years,(21.6 ± 3.3) kg/m2 and (1.6 ± 0.1) cm,respectively.There was no significant difference of those items between ultrasound and radical group.In ultrasound group,the transducer was placed at the dorsal and ventral to visualize the real time image of ipsilateral renal collecting system.The safety wire placing,ureteroscope passing through the uretheral access sheath and the lithotripsy detail could be easily monitored.We compared stone size,operative time,stone-free status and complication rates between the ultrasound and radical group.Results All patients accepted the operation successfully.Operative time was significantly shorter in the ultrasound group than that in radical group.[(62.4 ± 31.7) min vs.(80.4 ± 42.1)min,P ＜0.05].The average radical exposure during was (37.5 ± 25.2)seconds in radical group.Ureteral injury was seen in 20.0％ (13/65),18.5％ (12/65) cases in ultrasound and radical group,respectively.The mucosal injury rate in each group was 92.3％ (12/13) and 83.3％ (10/12) (P ＞ 0.05),respectively.Muscle layer injury was recorded in 1 case of in ultrasound group and 2 cases in radical group.Clavien grade Ⅳ or higher grade complications was not observed in both groups.Fever,pain,nausea or vomiting,persistent hematuria in ultrasound group were 2 cases,3 cases,1 cases and 5 cases.In radical group,those complications were in 2 cases,3 cases,7 cases and 1 cases,respectively.There was no significant difference between the two groups (P ＞ 0.05).The ultrasound group showed no significant difference in the stone-free rate [90.8％ (118/130)vs.89.2％ (116/130)] or the complication rate compared to those in radical group(P ＞ 0.05).Conclusions The retrograde intra-renal lithotripsy guided solely by ultrasound can be carried out in the general population in an effective and safe fashion without ionizing radiation,which has the potential to replace radical guided in flexible ureteroseopy.

Objective To evaluate if the flexible ureteroscopy could treat stones located in lower calyx with the infundibulopelvic angle (IPA) less than 30°.Methods Thirty-six patients with inferior caliceal calculi on whom flexible ureteroscopic procedures were performed between November 2009 and June 2015 were reviewed.The mean age of the patients was 52.1 years (34-71),with the mean stone diameter of (1.5 ± 0.8) cm (1.2-2.6 cm).IPA was smaller than 30° in all 36 cases,which confirmed by CTU examination.IPA was less than 10° in 15 patients,between 11 ° and 20° in 13 patients and between 21 ° and 30° in 8 patients.Results The success rate was 63.9％ (23/36 patients) in patients with IPA smaller than 30° after first session of procedure,and the stone free rate reached 100％ after the second session of procedure.The mean operation duration was (95.5 ± 31.4) min(51-127 min).The mean hospital stay after operation was(4.1 ± 1.2)days (3-5 days).No major complications were recorded and no patients needed to convert to open surgery.Double J tube was removed after 4 weeks postoperatively.Patients were followed up for 4-12 months,during which ultrasound and CT scan were used for stone detection.Conclusions The small IPA (＜30°) negatively affected the SFR in the first session operation.However,its negative effect was solvable by using modern endoscopes.A complete stone clearance was achievable even in case of unfavorable anatomic conditions in experienced hand.