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.

Gingival pigmentation(GP) manifests as dark pigmentation spots, such as black or brown spots, in the gums. It is mostly caused by the deposition of melanin particles secreted by melanocytes on the gingival epithelium. The influencing factors may be divided into two categories, exogenous and endogenous. Exogenous factors include heavy metals, tattoos, smoking or drug use, and endogenous factors are related to certain diseases. The clinical grading of GP helps make a reasonable assessment of the necessity of treatment and prognosis. The Dummett-Gupta oral pigmentation index is a commonly used grading method, and the new grading method formed by combining the etiology and clinical manifestations described the patient’s situation more comprehensively. It is necessary to ask for a detailed medical history, complete examination, and correctly differentiate between physiological GP and GP caused by pathological state. Laser treatment is the currenttreatment with a better treatment effect and higher patient acceptance, and it is more comfortable and convenient, including diode laser, Er: YAG laser, and Nd: YAG laser, etc. This article summarizes the formation factors, clinical manifestations and treatment methods of GP to provide ideas for the clinical diagnosis and treatment of GP.

Kidney stones are mixed by various inorganic salts and organic matter according to certain rules. The process of crystal nucleation, growth and aggregation is the key step of kidney stone formation. The different crystal structures will bring about the different formation process and physicochemical properties of kidney stones. It is of great significance to study the crystal structures and formation characteristics of kidney stone to clarify the causes of it and prevent the recurrence of it. In this paper, based on the microstructure and crystal structure of kidney stones, the distribution of different crystals and components in kidney stones, the nucleation and growth process of crystal forming kidney stones, and the different treatment methods based on crystal structure are reviewed in recent years.

The formation mechanism of kidney stones is complex. It is generally recognized that abnormal urine conditions or renal tubular epithelial cell damage, together with other factors cause the formation of renal papillary subepithelial calcium plaques (Randall’s plaques) or stone crystals that block the renal tubules (Randall’s plugs), and then oversaturated crystals gathering on Randall's plaque or plug and forming stones. However, there are many pathophysiological changes and manifestations, such as renal papillary anchoring stones, renal papillary crypts, renal papillary tip erosion, and exogenous renal papilla Renal papillary lesions, which may be an early manifestations before the formation of kidney stones. The study of renal papillary calcium plaque is very important for the pathogenesis of kidney stones, as well as the prevention and treatment of patients with stones. By focusing on the development process of Randall plaque theory, the formation and transformation mechanism of Randall plaque, as well as the manifestations and clinical treatment of the above mentioned different types of renal papillary calcium plaque lesions, this article reviewed three aspects of stone formation, including Randall’s plaque, renal papillary lesions with stones, and renal papillary lesions related to stone.

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 study the effect of Pterostilbene on endoplasmic reticulum stress and apoptosis in human renal tubular epithelial cells (HK-2 cells) induced by oxalate.Methods:From January 2019 to January 2020, HK-2 cells were divided into a control group (cultured with normal medium), an oxalate group (cultured with a medium containing 4 mmol/L of oxalate), and an intervention group of Pterostilbene (containing 4 mmol/L of oxalate + Pterostilbene 5, 10, and 20 μmol/L mixed medium were cultured at the same time), and the following tests were performed after 12 hours of treatment. Pterostilbene (5, 10, and 20 μmol/L) intervention group for cell viability test, lactate dehydrogenase cytotoxicity test, reduced glutathione, superoxide dismutase, malondialdehyde, hydrogen peroxide enzyme, total antioxidant capacity detection experiments to explore the degree of oxidative damage, and Western blotting experiments to explore the protein expression of ATF6, GRP78, DDIT3, caspase12, Clevead caspase 3/9; Pterostilbene (10 μmol/L) intervention group to detect mitochondrial membrane potential, caspase 3 enzyme activity, apoptosis rate, reactive oxygen detection to detect the apoptosis, reactive oxygen level, and qRT-PCR to detect ATF6, GRP78, DDIT3 of cells mRNA expression.Results:CCK-8 and lactate dehydrogenase toxicity test results showed that the cell activity of the oxalate group was significantly lower than that of the control group [(45.6±3.1)% vs. 100.0%, P<0.001]; the lactate dehydrogenase [(330.2±11.1)U/L vs. (2.6±6.7) U/L, P<0.001] of the oxalate group was higher than that of the control group increased obviously; the cell viability[ (57.2±1.7)%, (67.2±3.4)%, (78.9±1.8)%] of Pterostilbene intervention group (5, 10, 20 μmol/L) significantly increased compared with oxalate group ( P<0.05); lactate dehydrogenase [(288.1±4.3)U/L, (260.9±5.5)U, (202.7±10.2)U/L] in Pterostilbene intervention group (5, 10, 20 μmol/L ) was significantly lower than oxalate group ( P<0.05). The results of the five biochemical indexes of malondialdehyde, reduced glutathione, total superoxide dismutase, catalase, and total antioxidant capacity showed that the cell damage state was consistent with the experimental results of CCK-8 and lactate dehydrogenase. The active oxygen test results showed that the oxalate group had a significantly higher active oxygen level (76.3±4.9 vs. 6.2±1.7, P<0.01); the active oxygen level (39.5±5.4) of the Pterostilbene intervention group(10 μmol/L) was significantly lower than oxalate group ( P<0.01). The flow cytometry and caspase3 enzyme activity showed an increase in apoptosis rate and caspase3 activity in line with the trend of reactive oxygen levels. Mitochondrial membrane potential results showed that the oxalate group had a significantly lower mitochondrial membrane potential (0.76±0.15 vs. 7.84±0.26, P<0.01), and the mitochondrial membrane potential (2.26±0.27) of the Pterostilbene intervention group (10 μmol/L) was significantly higher than oxalate group( P<0.01). Western blot analysis showed that the relative expression of ATF6, DDIT3, GRP78, caspase12 and Cleaved caspase3/9 protein in the oxalate group was significantly higher than that in the control group. The relative expression of ATF6, DDIT3, GRP78, caspase12, Cleaved caspase3/9 protein in the Pterostilbene intervention group was significantly lower than that in the oxalate group ( P<0.05). qRT-PCR results showed that the mRNA expression trends of ATF6, DDIT3 and GRP78 in the three groups were consistent with the results of Western blotting. Conclusion:Pterostilbene can effectively inhibit the endoplasmic reticulum stress and apoptosis of HK-2 cells induced by oxalate.

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.

Endoscopic surgery has become the most common urological procedure for calculus in upper urinary tract. However, the widespread usage of minimally invasive endoscopic techniques failed to end the occurrence of perioperative complications, especially some fatal complications. The most severe complication of urolithiasis related endoscopic procedure is urosepsis, which is closely related to the backflow of irrigation fluid induced by the high pressure of renal pelvic during the procedure. By controlling the perfusion and drainage during the operation, the liquid backflow can be reduced effectively, thus may reduce the spread of infectious toxins and pathogens, and incidence of infectious complications can be controlled accordingly. In this article, the pathophysiology of urinary obstruction, the backflow which caused by elevated renal pelvic pressure and its subsequent pathophysiological changes, the control of intra-renal gressure and the prevention of urosepsis will be reviewed. The important range of intra-renal pressure and the major steps for pressure control during the operation is emphasized.