Objective:To evaluate the role of whole exome sequencing（WES）in the etiological diagnosis and precision medicine management of patients with urolithiasis.Methods:We conducted a retrospective review of 21 patients with urolithiasis and pathogenic gene mutations identified by WES at The Second Affiliated Hospital of Zhengzhou University between April 2019 and March 2025. The cohort included 13 males and 8 females，with a mean age of（18.9 ± 11.1）years；18 patients were under 25 years old. Clinical presentations included nephrocalcinosis（8 patients）and urinary tract calculi（13 patients），with five patients exhibiting extra-renal manifestations such as renal tubular acidosis and hyperaldosteronism. Stone composition analysis identified calcium oxalate（16 patients），cystine（4 patients），and carbonate apatite（1 patient）. Metabolic abnormalities were prevalent，including hypocitraturia（11 patients），hyperoxaluria（8 patients），and hypercalciuria（7 patients），with eight patients presenting two or more concurrent disorders. All patients underwent WES and comprehensive metabolic evaluation. Sequencing was performed on an Illumina Hiseq4000 platform，achieving a mean depth of > 100× and coverage of > 98% in target regions. Variants were classified according to the American College of Medical Genetics and Genomics（ACMG）guidelines.Results:WES identified 12 distinct genes across autosomal recessive（9 genes： AGXT， GRHPR， ATP6V1B1， SLC12A1， KCNJ1， SLC3A1， SLC7A9， SLC34A3， WFS1），autosomal dominant（2 genes： CASR， ADCY10），and X-linked recessive（1 gene： CLCN5）inheritance patterns. Genotype-phenotype correlations revealed mutations associated with primary hyperoxaluria（8 patients），hypercalciuria（7 patients），and renal malformation due to a WFS1 mutation（1 patient）. A positive genetic diagnosis was achieved in 100% of patients with either urinary oxalate > 1 000 μmol/24 h or cystine stones. 8 patients received a diagnosis of hereditary stone disease at their first presentation（non-delayed group），while 13 experienced a mean diagnostic delay of（9.6 ± 3.9）years. The delayed diagnosis group had a significantly older age at initial stone onset［（10.2 ± 5.3）years vs.（6.8 ± 3.1）years， P = 0.03］and a higher incidence of impaired renal function（6 patients vs. 1 patient， P = 0.04）. Analysis of diagnostic delay by gene subgroup showed delays in 2/4 patients with cystinuria［ SLC3A1/ SLC7A9；（8.2 ± 3.5）years］，5/8 with primary hyperoxaluria［ AGXT/ GRHPR；（10.5 ± 4.1）years］，5/7 with hypercalciuria-related genes［ CASR/ ADCY10/ SLC12A1/ KCNJ1/ SLC34A3；（9.8 ± 3.8）years］，and 1/2 with other genes［ ATP6V1B1/ WFS1/ CLCN5；（7.6 ± 2.2）years］. Among 32 mutation sites detected，21 were classified as pathogenic/likely pathogenic and 11 as variants of uncertain significance. Four novel mutations were identified： ATP6V1B1（presenting with renal tubular acidosis，nephrocalcinosis，and hypocitraturia）， WFS1（presenting with renal malrotation，hydronephrosis，and stones without metabolic abnormalities）， SLC12A1（presenting with Bartter syndrome type 1，chronic renal insufficiency，hypercalciuria，hypocitraturia，alkalosis，and hyperaldosteronism），and SLC3A1（presenting with bilateral renal stones and cystinuria）. Conclusions:WES is crucial in identifying the underlying etiology of urolithiasis and can guide targeted treatment. We recommend early WES for patients with an initial stone presentation before age 25，those with nephrocalcinosis，or those with abnormal metabolic workups to facilitate precise diagnosis and preventive care.

Objective To explore the clinical characteristics and risk factors of upper urinary tract stones complicated with non-alcoholic fatty liver disease(NAFLD),so as to provide reference for the prevention of this disease.Methods The clinical data of 158 NAFLD patients undergoing surgical treatment in our hospital during Jan.2022 and Jul.2023 were retrospectively analyzed.According to whether the patients were complicated with NAFLD,they were divided into the NAFLD group(n=56)and non-NAFLD group(n=102).The general data,laboratory indexes and 24-h urinary metabolic indexes were compared between the two groups,and the risk factors were analyzed with univariate and multivariate logistic regression analyses.Results Compared with the non NAFLD group,the NAFLD group had higher BMI[(28.17±4.17)vs.(24.11±3.72),P＜0.001],blood uric acid[(354.13±111.01)μmol/L vs.(294.41±93.72)μmol/L,P＜0.001],and 24-h urinary oxalate level[(37.74±15.00)mmol vs.(27.73±15.27)mmol,P＜0.001].Multivariate logistic analysis showed that BMI(OR=1.311,P＜0.001),24-h urinary oxalate(OR=1.046,P=0.004),and 24-h urinary magnesium(OR=0.599,P=0.002)were the independent factors for NAFLD with upper urinary tract stones.Conclusion NAFLD complicated with upper urinary tract stones is significantly associated with high BMI,high 24-h urinary oxalate,and low 24-h urinary magnesium.

Objective: To investigate the efficacy and safety of intelligent temperature-pressure-controlled flexible ureteroscopy combined with negative-pressure suction sheath lithotripsy in the treatment of upper urinary tract stones ≤2.5 cm. Methods: The clinical data of 225 patients with ≤2.5 cm upper urinary tract stones treated with this surgical method in our department during Aug. 2023 and Jul. 2024 were retrospectively analyzed. The patients were divided into the dual-control group (n=36) and conventional group (n=189) according to whether or not the intelligent temperature and pressure control device was used during operation. In the dual-control group，the intraoperative temperature and pressure in the renal pelvis were monitored and controlled in real time by the temperature and pressure sensors distributed at the end of the ureteral soft lens. The perioperative parameters，stone-removal rate，complication rate and renal function were compared between the two groups. Results: All operations were successfully completed in both groups. The postoperative procalcitonin (PCT) level [(22.75±5.85) ng/L vs. (29.08±6.60) ng/L，P=0.001]，difference in the white blood cell (WBC) level [(0.24±2.12)×10 cells/L vs. (1.19±2.17)×10 cells/L，P=0.016]，incidence of fever (2.8% vs. 16.9%，P=0.028) and overall complication rate (5.6% vs. 19.6%，P=0.042) were significantly lower in the dual-control group than in the conventional group，while the stone-clearance rate was slightly higher (88.9% vs. 82.5%，P=0.346)，with no significant difference. Conclusion: For upper urinary tract stones ≤2.5 cm，intelligent temperature-pressure-controlled ureteroscopy combined with negative-pressure suction sheath lithotripsy has a satisfactory stone-removal rate and a low rate of complications，which is worthy of clinical promotion.

Objective To explore the clinical characteristics and risk factors of upper urinary tract stones complicated with non-alcoholic fatty liver disease(NAFLD),so as to provide reference for the prevention of this disease.Methods The clinical data of 158 NAFLD patients undergoing surgical treatment in our hospital during Jan.2022 and Jul.2023 were retrospectively analyzed.According to whether the patients were complicated with NAFLD,they were divided into the NAFLD group(n=56)and non-NAFLD group(n=102).The general data,laboratory indexes and 24-h urinary metabolic indexes were compared between the two groups,and the risk factors were analyzed with univariate and multivariate logistic regression analyses.Results Compared with the non NAFLD group,the NAFLD group had higher BMI[(28.17±4.17)vs.(24.11±3.72),P＜0.001],blood uric acid[(354.13±111.01)μmol/L vs.(294.41±93.72)μmol/L,P＜0.001],and 24-h urinary oxalate level[(37.74±15.00)mmol vs.(27.73±15.27)mmol,P＜0.001].Multivariate logistic analysis showed that BMI(OR=1.311,P＜0.001),24-h urinary oxalate(OR=1.046,P=0.004),and 24-h urinary magnesium(OR=0.599,P=0.002)were the independent factors for NAFLD with upper urinary tract stones.Conclusion NAFLD complicated with upper urinary tract stones is significantly associated with high BMI,high 24-h urinary oxalate,and low 24-h urinary magnesium.

Objective:To investigate the independent risk factors for the occurrence of early urinary incontinence after Holmium laser enucleation of the prostate(HoLEP), and to construct a clinical risk predictive model for postoperative urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 384 patients who underwent HoLEP between February 2019 and July 2024 at the Second Affiliated Hospital of Zhengzhou University. The cohort had a mean age of (68.3 ± 6.5) years, with a body mass index (BMI) of 22.45 (20.11, 24.39) kg/m 2. The median duration of lower urinary tract symptoms was 60 (36, 60) months. Of the patients, 104 (27.1%) had a history of diabetes mellitus, 139 (36.2%) had hypertension, and 54 (14.1%) had a preoperative indwelling urinary catheter. Additionally, 136 patients (35.4%) had a preoperative prostate-specific antigen (PSA) level ≥ 4 ng/ml, and 197 patients (51.3%) had a preoperative residual urine volume ≥ 50 ml. The International Prostate Symptom Score (IPSS) was ≥ 19 in 227 cases (59.1%). Preoperative detrusor instability was observed in 169 cases (44.0%), with a median maximal urinary flow rate of 5.9 (4.5, 9.3) ml/s and a median urinary flow rate of 4.0 (3.4, 7.3) ml/s. Moreover, 148 cases (38.5%) had a preoperative prostate volume ≥ 65 ml, and the preoperative median maximum urethral length (MUL) was 13.99 (12.40, 16.24) mm. Postoperative follow-up allowed for division of the patients into two groups: those with recovery of urinary control function and those with early postoperative urinary incontinence. The general characteristics of both groups were compared. Independent risk factors for early postoperative urinary incontinence were identified through multifactorial logistic regression. Variables with statistically significant differences were included in a column chart model created using R software. Internal validation was performed through repeated sampling with the Bootstrap method to assess the model's discriminative ability. Calibration curves were plotted to examine the consistency between predicted and actual outcomes, and the Hosmer-Lemeshow test was used to evaluate the model's fit. Results:This study included 384 patients, with 313 in the urinary control function recovery group and 71 in the early incontinence group. There were statistically significant difference between the two groups in age [≥70 years old: 91 (29.1%) vs. 33 (46.5%)], prostate volume [≥65 ml: 110 (35.1%) vs. 38 (53.5%)], MUL [14.21 (12.63, 16.24) mm vs. 13.12 (12.21, 13.95) mm], and non-inhibitory contraction of the urethra muscle in both groups [125 (39.9%) vs. 44 cases (62.0%)] ( P < 0.05). No significant differences were observed between the two groups in terms of BMI, disease duration, history of diabetes mellitus, preoperative catheterization, IPSS, preoperative PSA, residual bladder urine volume, maximum urinary flow rate, average urinary flow rate, operative time, or duration of indwelling urinary catheterization ( P > 0.05). Multifactorial logistic regression analysis revealed that age ≥ 70 years ( OR = 0.414, 95% CI 0.230-0.746, P = 0.003), prostate volume ≥ 65 ml ( OR=0.451, 95% CI 0.251-0.812, P=0.008), MUL( OR=0.688, 95% CI 0.590-0.802, P<0.001), and detrusor instability, uninhibited detrusor contraction ( OR=0.526, 95% CI 0.279-0.994, P=0.048) were independent risk factors for early postoperative urinary incontinence following HoLEP. A prediction model was developed based on these findings, and internal validation showed a C-index of 0.753. The calibration curve was close to the ideal curve, indicating that the model has good predictive performance. Conclusions:Age ≥70 years, prostate volume ≥65 ml, MUL, and uninhibited contraction of the urethra muscle were independent influences on early urinary incontinence after HoLEP, and the nomogram constructed in this way had good predictive performance for the risk of developing early urinary incontinence after HoLEP.

Objective:To investigate the independent risk factors for the occurrence of early urinary incontinence after Holmium laser enucleation of the prostate(HoLEP), and to construct a clinical risk predictive model for postoperative urinary incontinence.Methods:A retrospective analysis was conducted on the clinical data of 384 patients who underwent HoLEP between February 2019 and July 2024 at the Second Affiliated Hospital of Zhengzhou University. The cohort had a mean age of (68.3 ± 6.5) years, with a body mass index (BMI) of 22.45 (20.11, 24.39) kg/m 2. The median duration of lower urinary tract symptoms was 60 (36, 60) months. Of the patients, 104 (27.1%) had a history of diabetes mellitus, 139 (36.2%) had hypertension, and 54 (14.1%) had a preoperative indwelling urinary catheter. Additionally, 136 patients (35.4%) had a preoperative prostate-specific antigen (PSA) level ≥ 4 ng/ml, and 197 patients (51.3%) had a preoperative residual urine volume ≥ 50 ml. The International Prostate Symptom Score (IPSS) was ≥ 19 in 227 cases (59.1%). Preoperative detrusor instability was observed in 169 cases (44.0%), with a median maximal urinary flow rate of 5.9 (4.5, 9.3) ml/s and a median urinary flow rate of 4.0 (3.4, 7.3) ml/s. Moreover, 148 cases (38.5%) had a preoperative prostate volume ≥ 65 ml, and the preoperative median maximum urethral length (MUL) was 13.99 (12.40, 16.24) mm. Postoperative follow-up allowed for division of the patients into two groups: those with recovery of urinary control function and those with early postoperative urinary incontinence. The general characteristics of both groups were compared. Independent risk factors for early postoperative urinary incontinence were identified through multifactorial logistic regression. Variables with statistically significant differences were included in a column chart model created using R software. Internal validation was performed through repeated sampling with the Bootstrap method to assess the model's discriminative ability. Calibration curves were plotted to examine the consistency between predicted and actual outcomes, and the Hosmer-Lemeshow test was used to evaluate the model's fit. Results:This study included 384 patients, with 313 in the urinary control function recovery group and 71 in the early incontinence group. There were statistically significant difference between the two groups in age [≥70 years old: 91 (29.1%) vs. 33 (46.5%)], prostate volume [≥65 ml: 110 (35.1%) vs. 38 (53.5%)], MUL [14.21 (12.63, 16.24) mm vs. 13.12 (12.21, 13.95) mm], and non-inhibitory contraction of the urethra muscle in both groups [125 (39.9%) vs. 44 cases (62.0%)] ( P < 0.05). No significant differences were observed between the two groups in terms of BMI, disease duration, history of diabetes mellitus, preoperative catheterization, IPSS, preoperative PSA, residual bladder urine volume, maximum urinary flow rate, average urinary flow rate, operative time, or duration of indwelling urinary catheterization ( P > 0.05). Multifactorial logistic regression analysis revealed that age ≥ 70 years ( OR = 0.414, 95% CI 0.230-0.746, P = 0.003), prostate volume ≥ 65 ml ( OR=0.451, 95% CI 0.251-0.812, P=0.008), MUL( OR=0.688, 95% CI 0.590-0.802, P<0.001), and detrusor instability, uninhibited detrusor contraction ( OR=0.526, 95% CI 0.279-0.994, P=0.048) were independent risk factors for early postoperative urinary incontinence following HoLEP. A prediction model was developed based on these findings, and internal validation showed a C-index of 0.753. The calibration curve was close to the ideal curve, indicating that the model has good predictive performance. Conclusions:Age ≥70 years, prostate volume ≥65 ml, MUL, and uninhibited contraction of the urethra muscle were independent influences on early urinary incontinence after HoLEP, and the nomogram constructed in this way had good predictive performance for the risk of developing early urinary incontinence after HoLEP.

Objective:To evaluate the role of whole exome sequencing（WES）in the etiological diagnosis and precision medicine management of patients with urolithiasis.Methods:We conducted a retrospective review of 21 patients with urolithiasis and pathogenic gene mutations identified by WES at The Second Affiliated Hospital of Zhengzhou University between April 2019 and March 2025. The cohort included 13 males and 8 females，with a mean age of（18.9 ± 11.1）years；18 patients were under 25 years old. Clinical presentations included nephrocalcinosis（8 patients）and urinary tract calculi（13 patients），with five patients exhibiting extra-renal manifestations such as renal tubular acidosis and hyperaldosteronism. Stone composition analysis identified calcium oxalate（16 patients），cystine（4 patients），and carbonate apatite（1 patient）. Metabolic abnormalities were prevalent，including hypocitraturia（11 patients），hyperoxaluria（8 patients），and hypercalciuria（7 patients），with eight patients presenting two or more concurrent disorders. All patients underwent WES and comprehensive metabolic evaluation. Sequencing was performed on an Illumina Hiseq4000 platform，achieving a mean depth of > 100× and coverage of > 98% in target regions. Variants were classified according to the American College of Medical Genetics and Genomics（ACMG）guidelines.Results:WES identified 12 distinct genes across autosomal recessive（9 genes： AGXT， GRHPR， ATP6V1B1， SLC12A1， KCNJ1， SLC3A1， SLC7A9， SLC34A3， WFS1），autosomal dominant（2 genes： CASR， ADCY10），and X-linked recessive（1 gene： CLCN5）inheritance patterns. Genotype-phenotype correlations revealed mutations associated with primary hyperoxaluria（8 patients），hypercalciuria（7 patients），and renal malformation due to a WFS1 mutation（1 patient）. A positive genetic diagnosis was achieved in 100% of patients with either urinary oxalate > 1 000 μmol/24 h or cystine stones. 8 patients received a diagnosis of hereditary stone disease at their first presentation（non-delayed group），while 13 experienced a mean diagnostic delay of（9.6 ± 3.9）years. The delayed diagnosis group had a significantly older age at initial stone onset［（10.2 ± 5.3）years vs.（6.8 ± 3.1）years， P = 0.03］and a higher incidence of impaired renal function（6 patients vs. 1 patient， P = 0.04）. Analysis of diagnostic delay by gene subgroup showed delays in 2/4 patients with cystinuria［ SLC3A1/ SLC7A9；（8.2 ± 3.5）years］，5/8 with primary hyperoxaluria［ AGXT/ GRHPR；（10.5 ± 4.1）years］，5/7 with hypercalciuria-related genes［ CASR/ ADCY10/ SLC12A1/ KCNJ1/ SLC34A3；（9.8 ± 3.8）years］，and 1/2 with other genes［ ATP6V1B1/ WFS1/ CLCN5；（7.6 ± 2.2）years］. Among 32 mutation sites detected，21 were classified as pathogenic/likely pathogenic and 11 as variants of uncertain significance. Four novel mutations were identified： ATP6V1B1（presenting with renal tubular acidosis，nephrocalcinosis，and hypocitraturia）， WFS1（presenting with renal malrotation，hydronephrosis，and stones without metabolic abnormalities）， SLC12A1（presenting with Bartter syndrome type 1，chronic renal insufficiency，hypercalciuria，hypocitraturia，alkalosis，and hyperaldosteronism），and SLC3A1（presenting with bilateral renal stones and cystinuria）. Conclusions:WES is crucial in identifying the underlying etiology of urolithiasis and can guide targeted treatment. We recommend early WES for patients with an initial stone presentation before age 25，those with nephrocalcinosis，or those with abnormal metabolic workups to facilitate precise diagnosis and preventive care.

【Objective】 To establish a nomogram model for predicting the risk of positive prostate biopsy in MRI-negative patients, and to perform the internal validation. 【Methods】 We retrospectively analyzed the clinical data of 197 MRI-negative patients who underwent prostate biopsy at our hospital, analyzed the independent predictors of positive prostate biopsy with univariate and multivariate logistic regression analysis, constructed the nomogram model and conducted internal validation. 【Results】 Multivariate logistic regression analysis showed age (P=0.003), digital rectal examination (DRE)(P=0.005), total prostate-specific antigen (tPSA) (P=0.001) and prostate volume (PV)(P<0.001) were independent risk factors of MRI-negative but prostate biopsy-positive results. The nomogram model based on all variables was established. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.862, which was greater than that of tPSA (AUC=0.739), PV(AUC=0.711) and DRE(AUC=0.666) (all P<0.05). The average absolute error of the model was 1.1% after 500 internal resampling, indicating that the prediction of positive prostate biopsy was consistent with the actual situation. 【Conclusion】 The age, DRE, tPSA and PV were independent predictors of positive prostate biopsy in MRI-negative patients. The nomogram model has a good prediction performance.

Objective:To investigate the difference of 24h urinary metabolic abnormalities in patients with different subtypes of calcium oxalate stones.Methods:The clinical data of 120 patients with simple calcium oxalate stones admitted to the Second Affiliated Hospital of Zhengzhou University from March 2018 to May 2020 were retrospectively analyzed.There were 90 males (75.0%) and 30 females (25.0%), with the age of (49.1 ±13.5) years old, and body mass index (BMI) of (24.6 ±3.0) kg/m 2. There were 23 cases of diabetes mellitus (19.2%), 8 cases of coronary heart disease (7.0%), 36 cases of hypertension (30.0%) and 45 cases of gastrointestinal diseases (37.5%). There were 11 cases (9.2%) of low pH, 54 cases (45.0%) of hyperoxaluria, 19 cases (15.8%) of hypercalcemia, 72 cases (60.0%) of hypocitrouria, 3 cases (2.5%) of hyperuricuria, and 18 cases (15.0%) of hyperuricemia. In the 120 patients, 79 underwent ureteral soft lithotripsy, 28 underwent percutaneous nephrolithotomy, and 13 underwent extracorporeal shock wave lithotripsy. The patients were divided into calcium oxalate monohydrate stone group (COM group) and calcium oxalate dihydrate stone group (COD group). The general clinical data and urinary metabolic data of the two groups were compared. Independent risk factors for stone formation of the two groups were analyzed. Results:There were 120 cases in this study, with 90 cases in COM group and 30 cases in COD group. Urinary oxalic acid in COM group and COD group was 41.3 (30.1, 54.2) mg and 34.1 (26.6, 39.9) mg, respectively, and the difference was statistically significant ( P=0.01). The incidence of hyperoxaluria was 52.2% (47 cases) and 23.3% (7 cases), respectively, and the difference was statistically significant ( P<0.01). Urinary calcium in COD group and COM group was 6.8 (6.1, 8.8) mmol and 4.0 (2.3, 5.2) mmol, respectively, and the difference was statistically significant ( P<0.01). The incidence of hypercalcemia was 43.3% (13 cases) and 6.7% (6 cases), respectively, the difference was statistically significant ( P<0.01). The urinary phosphate in COM group and COD group was 2 063.5 (1 688.8, 2 803.2) mg and 1 231.7 (766.7, 1 740.9) mg, respectively, and the difference was statistically significant ( P<0.01). The serum uric acid level in COM group and COD group was (343.0±111.7)μmol/L and (297.6±77.6)μmol/L, respectively, and the difference was statistically significant ( P<0.05). There were no significant differences in term of age, gender, body mass index, diabetes mellitus, coronary heart disease, hypertension, gastrointestinal disease, parathyroid hormone (PTH), hemoglobin, serum creatinine, serum potassium, serum phosphorus, serum calcium, serum sodium, stone load and side between the two groups ( P>0.05). There were no significant differences in urinary sodium, urinary phosphorus, urinary magnesium, urinary citric acid and urinary uric acid levels between the two groups ( P>0.05). Binary Logistic regression analysis showed that hyperoxaluria was an independent risk factor for COM patients ( OR=4.859, P<0.01). Increased urinary phosphoric acid level was an independent risk factor for COM patients ( OR=1.001, P<0.01). Hypercalcemia was an independent risk factor for COD patients ( OR=27.856, P<0.01). Conclusions:COM calculus patients have higher urinary oxalic acid and urinary phosphoric acid levels, and are more likely to have hyperoxaluria. COD calculus patients have higher urinary calcium levels and are more likely to develop hypercalcemia.

Humans ; Femoral Artery/surgery* ; Hip Dislocation, Congenital ; Hip Joint ; Treatment Outcome