Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.

The pathogenesis of renal calcium-oxalate (CaOx) stones is complex and influenced by various metabolic factors. In parallel, palmitic acid (PA) has been identified as an upregulated lipid metabolite in the urine and serum of patients with renal CaOx stones via untargeted metabolomics. Thus, this study aimed to mechanistically assess whether PA is involved in stone formation. Lipidomics analysis of PA-treated renal tubular epithelial cells compared with the control samples revealed that α-linoleic acid and α-linolenic acid were desaturated and elongated, resulting in the formation of downstream polyunsaturated fatty acids (PUFAs). In correlation, the levels of fatty acid desaturase 1 and 2 (FADS1 and FADS2) and peroxisome proliferator-activated receptor α (PPARα) in these cells treated with PA were increased relative to the control levels, suggesting that PA-induced upregulation of PPARα, which in turn upregulated these two enzymes, forming the observed PUFAs. Lipid peroxidation occurred in these downstream PUFAs under oxidative stress and Fenton Reaction. Furthermore, transcriptomics analysis revealed significant changes in the expression levels of ferroptosis-related genes in PA-treated renal tubular epithelial cells, induced by PUFA peroxides. In addition, phosphatidyl ethanolamine binding protein 1 (PEBP1) formed a complex with 15-lipoxygenase (15-LO) to exacerbate PUFA peroxidation under protein kinase C ζ (PKC ζ) phosphorylation, and PKC ζ was activated by phosphatidic acid derived from PA. In conclusion, this study found that the formation of renal CaOx stones is promoted by ferroptosis of renal tubular epithelial cells resulting from PA-induced dysregulation of PUFA and phosphatidic acid metabolism, and PA can promote the renal adhesion and deposition of CaOx crystals by injuring renal tubular epithelial cells, consequently upregulating adhesion molecules. Accordingly, this study provides a new theoretical basis for understanding the correlation between fatty acid metabolism and the formation of renal CaOx stones, offering potential targets for clinical applications.

Vacuum-assisted dedusting lithotripsy in the treatment of kidney and proximal ureteral stones less than 3 cm in size.

PURPOSE: This study aimed to compare the outcomes of vacuum-assisted dedusting lithotripsy (VADL) using flexible vacuum-assisted ureteral access sheath (FV-UAS) versus traditional flexible ureteroscopic lithotripsy (fURL) in patients with kidney or proximal ureteral calculi less than 3 cm in size. METHODS: A total of 371 patients who successfully underwent fURL treatment were enrolled. These patients were divided into traditional fURL group and VADL group. Outcomes of both groups were compared using 1:1 propensity score-matched analysis. Stratified analyses based on stone size and location were also conducted. RESULTS: Finally, 103 well-matched patients in each group were identified. No septic shock or death occurred. The immediate stone-free rate (SFR) and follow-up SFR of VADL group were significantly higher (78.6% vs. 50.5%, p < 0.001; 94.2%% vs. 75.7%, p < 0.001). No difference was observed in postoperative fever rate (2.9% vs. 3.9%, p = 1.000) and duration of lithotripsy (37.7 ± 20.1 min vs. 40.3 ± 18.9 min, p = 0.235). For patients with stones ≤ 2 cm in size, the immediate SFR and follow-up SFR in VADL group were higher (86.7% vs. 60.6%, p < 0.001; 96.0% vs. 83.1%, p = 0.010). The same trend was observed in the 2-3 cm subgroup (57.1% vs. 28.1%, p = 0.023; 89.3% vs. 59.4%, p = 0.009). Although the in situ fragmentation strategy was employed more frequently in VADL group for lower pole stones, the SFR was still higher. Subgroup analyses did not reveal any significant differences in either infectious complications or duration of lithotripsy. CONCLUSION: VADL technique can significantly improve the postoperative SFR for the patients with kidney or proximal ureteral stones less than 3 cm in size treated by flexible ureteroscope.

A modified triangular Double-J stent for retrograde intrarenal surgery improvement of free-stone rate, and quality of life: a randomized controlled, multiple centers, perspective trial.

PURPOSE: The goal of this study is to evaluate the efficacy and safety of modified triangular double-J (DJ) stent in 1-2 cm renal or ureter calculi after retrograde intrarenal surgery (RIRS) via a randomized, controlled clinical study. METHODS: A total of 196 patients with 1-2 cm renal or ureter calculi who were performed RIRS and received 7Fr modified triangular DJ stents (100 cases) or 6Fr normal DJ stents (96 cases). All operations were performed by experienced surgeons. The clinical characteristics and outcomes were analyzed. RESULTS: There were no significant differences between two groups in terms of age, gender, BMI, location, hydronephrosis, urea WBC, urea RBC, BUN, Cr, laser emission time, operation time, Hb loss, postoperative BUN, postoperative Cr. Patients who received modified triangular DJ stents were shown to have higher stone-free rate (p = 0.038), but lower general health (p = 0.004). CONCLUSION: The modified triangular 7Fr DJ stents were more efficient for patients underwent RIRS than 6Fr normal DJ stents.

Hypoalbuminemia within One Hour After Surgery as a Predictor of Post-Operative Urosepsis in Patients Undergoing Flexible Ureteroscopy Lithotripsy: A Retrospective Study.

Abstract Background: To investigate retrospectively whether changes in serum albumin levels within one hour of flexible ureteroscopy (fURS) lithotripsy can be used as a predictor of post-operative urosepsis. Patients and Methods: Eligible patients with unilateral upper urinary calculi who underwent fRUS lithotripsy performed by a single surgeon at our center were included in the analysis. The patients were divided into sepsis and non-sepsis groups. The change ratio of albumin and white blood cell (WBC) count was calculated by post-operative/pre-operative index*100%. Univariable and multivariable logistic regression analyses were used to assess whether there was a correlation between risk factors and post-operative urosepsis. The receiver operating characteristic (ROC) curve was used to analyze factors that showed significant differences in multivariable logistic regression analysis. Results: A total of 314 patients were included in the analysis, 20 of whom had post-operative urosepsis and five developed septic shock; no deaths occurred. Multivariable logistic regression analysis showed that urine culture results, WBC counts within one hour after surgery, post-operative albumin levels, and the degree of albumin changes after surgery were independent predictors of post-operative urosepsis. Receiver operating characteristic curve analysis showed that noteworthy hypoalbuminemia after surgery and positive pre-operative urine culture could help screen high-risk patients for post-operative urosepsis effectively. Conclusions: Hypoalbuminemia shortly after operation can be utilized as a predictor for early diagnosis of post-operative urosepsis in patients undergoing fURS lithotripsy.

Study on the pathogenesis and prevention strategies of kidney stones based on GC-MS combined with metabolic pathway analysis.

RATIONALE: Most kidney stone composition analyses include organic compounds, and only few organic volatile compounds have been reported. METHODS: In the present study, a novel approach for studying the pathogenesis and prevention of kidney stones was established. First, common organic volatile compounds were detected using gas chromatography-mass spectrometry (GC-MS) in 137 kidney stone samples. The Kyoto Encyclopedia of Genes and Genomes database and MetaboAnalyst 5.0 software were then used to analyze the metabolic pathways associated with the development of kidney stones. RESULTS: The metabolic pathway analysis of the common component cholesterol revealed that two metabolic pathways, the steroid biosynthesis pathway and the primary bile acid biosynthesis pathway, were closely associated with the formation of kidney stones. The pretreatment process for stone analysis, including the solvent type, solvent volume, and extraction time, was optimized to improve the detection efficiency. The calibration curve was y = 756 299x - 8 000 000, with a correlation coefficient (r) of 0.9992, which was obtained over the concentration range of 10-500 µg ml-1 of cholesterol. The recovery values of cholesterol ranged from 93.34% to 94.67%, 96.98% to 99.23%, and 87.27% to 93.00% when spiked with 0.75, 1.00, and 1.25 µg, respectively, with a relative standard deviation of no less than 3.18%. Finally, the content of common compounds was determined in 37 renal stone samples using the modified GC-MS method. CONCLUSIONS: The common organic volatile compound in the kidney stone samples detected using GC-MS was cholesterol, and the steroid biosynthesis and primary bile acid biosynthesis pathways were determined to be closely associated with the formation of kidney stones. The GC-MS method for detecting cholesterol in kidney stones was optimized for efficiency and accuracy.

Epidemiological and clinical characteristics of stone composition: a single-center retrospective study.

The aim of the study was to investigate the epidemiological characteristics of stone components in patients with urolithiasis and analyze the associations between stone components with patients' clinical characteristics. A total of 7126 patients with urolithiasis between July 2005 and June 2020 were retrospectively analyzed. In this research, calcium oxalate stones (74.6%) accounted for the highest proportion, followed by infection stones (11.8%), uric acid (10.6%), brushite (2.0%), and others (1.1%). The change in trend in the composition of urinary stones revealed that the proportion of uric acid declined steadily, while the content of infection stones increased gradually over 15 years. The results also suggested that stone composition was significantly associated with PM2.5, gender, age, BMI, diabetes, hypertension, CCVD, alcohol consumption, albumin, creatinine, WBCHP, leukocyte, urine pH, nitrite and urine culture (P < 0.05). However, there was no significant correlation between stone composition with smoking, WBC and NEU% (P > 0.05). Our study concluded that calcium oxalate represented the highest proportion, followed by infection stones, uric acid, brushite, and others. The proportion of uric acid declined steadily, while the infection stones increased gradually. Furthermore, the factors influencing the formation of urinary calculi are PM2.5, gender, age, BMI, diabetes, hypertension, CCVD, alcohol consumption, albumin, creatinine, WBCHP, leukocyte, urine pH, nitrite and urine culture. Collectively, these results may provide clues to establish effective prevention and management strategies for urinary calculi.

Novel Use of a Modified Triangular Prismatic Double-J Stent for 2- to 3-cm Renal Stones after One-Stage Retrograde Intrarenal Surgery.

OBJECTIVES: To initially evaluate the outcomes of the modified triangular prismatic double-J (DJ) stent in the management of 2- to 3-cm renal stones after one-stage retrograde intrarenal surgery (RIRS). METHODS: Patients with 2- to 3-cm renal stones who underwent one-stage RIRS with indwelling DJ stents were retrospectively evaluated. Eighty-eight patients who were placed the triangular prismatic DJ stents and 64 patients who received standard DJ stents were randomly included. The clinical characteristics and intraoperative and postoperative outcomes of the 2 groups were compared and analyzed. RESULTS: The 2 groups had similar baseline characteristics. The urinary symptom score and pain score did not differ between groups (p > 0.05). The residual fragments of the 2 groups were similar 1 day after operation (p = 0.134). There was no significant difference in residual fragments in the lower calyx between groups at the time of stent removal (p = 0.834). The patients in the modified group had better spontaneous passage of residual fragments in the nonlower calyx than those in the standard group during the 2 weeks with the stents (p = 0.005). Fewer patients in the modified group had residual fragments (>4 mm) in the nonlower calyx (p = 0.026) and ureter (p = 0.010) than the patients with standard stents at the time of stent removal. CONCLUSION: The indwelling triangular prismatic DJ stent is a safe and efficient treatment method. Patients with these stents had better spontaneous residual fragment passage than those with the standard DJ stents.

The visual percutaneous nephrolithotomy versus the conventional percutaneous nephrolithotomy in treatment for renal stone.

BACKGROUND: To report our initial experience using a self-made optical system to visually identify the quality of the chosen access before the operating tract dilation. METHODS: We retrospectively reviewed the data on patients with renal stones treated by percutaneous nephrolithotomy (PCNL) in our hospital. The patients were divided into Groups A and B, according to those who received treatment by visual PCNL and conventional PCNL modalities, respectively. Based on the degree of hydronephrosis, the patients in each group were further divided into two subgroups, the patients with mild hydronephrosis (subgroup 1) and the patients with moderate or severe hydronephrosis (subgroup 2). The demographics and perioperative parameters were analyzed. RESULTS: The study included 124 patients who underwent PCNL. Group A (N.=62): 47 patients were assigned to subgroup 1 and 15 to subgroup 2; group B (N.=62): 40 patients were assigned to r subgroup 1 and 22 to subgroup 2. The demographics were not significantly different between Group A and Group B (P>0.05). The puncture times were shorter in Group A and in subgroups (P<0.01), whereas the access loss rates were not significantly different (P>0.05). The mean decrease in hemoglobin levels, repuncture rates, blood transfusions and hospitalization times in Group A and Group A subgroup 1 were significantly lower than in Group B and Group B subgroup 1, respectively, (P<0.05), but no significant differences in subgroup 2 (P>0.05). When the complications were compared, the collecting system injury rates were significantly different between the two groups and in subgroup 1 (P<0.05). However the rates of fever and urinary sepsis were not statistically different in the two groups and in the subgroups (P>0.05). CONCLUSIONS: We found that visual PCNL was a safe and efficacious treatment for renal stones that may be considered as an alternative to conventional PCNL, especially in patients with mild hydronephrosis. Further prospective randomized controlled trials are needed to confirm the results of this study.

Total flavone of Desmodium styracifolium relieved apoptosis and autophagy of COM-induced HK-2 cells by regulating KIM-1 via p38/MAPK pathway.

The purpose of the study was to investigate the mechanism of total flavone of Desmodium styracifolium (TFDS) in regulating the formation of urinary calculi. Protein levels of KIM-1, LC3-II, p-p38 were measured by Western blot. The effect of different COM concentrations, different TFDS concentrations, SB203580 (specific inhibitor of p38/MAPK), and overexpression of KIM-1 on cell viability were detected by WST-1 assay. The apoptotic cells and FITC positive cells were detected by flow cytometry. HK-2 cell viability decreased with the increase of COM concentration, and the protein levels of KIM-1, LC3-II, and p-p38 increased with the time. Blocking the p38/MAPK pathway or co-cultured with TFDS inhibited the effects of COM on apoptosis and autophagy of HK-2 cells. In addition, blocking the p38/MAPK pathway inhibited the expression of KIM-1. In COM-induced cells, after treated with SB203580, overexpression of KIM-1 could reverse the protection effect of SB203580 on COM-induced cell damage and the inhibition of SB203580 on COM-induced excessive autophagy, suggesting p38/MAPK regulated KIM-1 to regulate COM-induced cell apoptosis and autophagy. Finally, we proved that TFDS inhibited p38/MAPK pathway. And the protection effect of COM-induced cell injury increased with the increase of TFDS concentration, and the adhesion between COM and cells decreased with the increase of TFDS concentration. With the increase of the concentration of TFDS, p38/MAPK pathway was gradually inhibited, and KIM-1 and autophagy related proteins were decreased. TFDS inhibited HK-2 cell apoptosis and autophagy by regulating KIM-1 via p38/MAPK pathway.

Association of PTEN expression with biochemical recurrence in prostate cancer: results based on previous reports.

PURPOSE: Among men, prostate cancer (PCa) is one of the most commonly diagnosed cancers and the leading cause of cancer death worldwide. Phosphatase and tension homolog (PTEN) acts as a negative regulator of the phosphatidylinositol 3-kinase (PIK3)/Akt pathway and suppresses tumor progression. Meanwhile, PTEN is frequently deleted in PCa. Identifying the specific molecular markers of biochemical recurrence (BCR) in PCa patients is critical in clinical practice. Our systematic review summarizes the evidence about the PTEN expression and BCR rate in PCa patients. METHODS: To clarify the impact of PTEN expression on the PCa BCR rate, a systematic review and meta-analysis was performed by searching the PubMed, Embase, and Web of Science databases, to identify the relevant literature. The analysis of pooled data was performed with Stata 12. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were evaluated by the fixed-effects or random-effects models. The combined sensitivity and publication bias were also estimated. RESULTS: In total, nine articles containing ten independent cohort studies, including 2,154 cases with positive expression of PTEN and 1,006 PTEN deletion cases, were deemed eligible for the meta-analysis. Overall, the positive expression of PTEN was associated with a significantly lower BCR rate (OR =0.521, 95% CI: 0.431-0.630). Subgroup analysis stratified by race revealed that in multiple races (OR =0.215, 95% CI: 0.072-0.648) and Caucasian (OR =0.469, 95% CI: 0.373-0.591) races, positive expression of PTEN showed a significant association with lower BCR rate. Subgroup analysis also showed the significant result in different sample sizes. CONCLUSION: PTEN deletion has a relationship with a higher BCR rate in PCa compared with positive expression of PTEN.