A novel post-percutaneous nephrolithotomy sepsis prediction model using machine learning.

OBJECTIVES: To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. METHODS: A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. RESULTS: Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. CONCLUSION: Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.

Development and validation of the UCSS score, a novel method to predict septic shock after PCNL.

OBJECTIVE: To develop an objective and easily recognizable model to predict septic shock following percutaneous nephrolithotomy (PCNL). SUBJECTS AND METHODS: First, we identified differences between 431 patients who underwent PCNL with or without septic shock. These data were used to develop existing models and examine their improvement. Multivariate analysis was applied to identify risk factors of septic shock after PCNL based on the scores allocated to the PCNL postoperative test indicators. Finally, we developed a predictive nomogram using the selected factors and compared its performance with that of the existing nomograms SOFA, qSOFA, and SIRS. RESULTS: Twelve (2.8%) of the patients met the criteria for postoperative septic shock after PCNL. Baseline data analysis revealed differences in sex, preoperative drainage, urinary culture, and urinary leukocyte between groups. After transforming patient data into measurement-level data, we investigated each index score in these conditions, and found that the incidence of septic shock generally increased with the score. Multivariate analysis and early optimization screening revealed that septic shock factors could be predicted using platelets, leukocytes, bilirubin, and procalcitonin levels. We further compared the prediction accuracy of urinary calculi-associated septic shock (UCSS), SOFA, qSOFA, and SIRS scores using the AUC of the ROC curve. As compared to SIRS [AUC 0.938 (95% CI 0.910-0.959)] and qSOFA [AUC 0.930 (95% CI 0.901-0.952)], UCSS [AUC 0.974 (95% Cl 0.954-0.987)] and SOFA [AUC 0.974 (95% CI 0.954-0.987)] scored better at discriminating septic shock after PCNL. We further compared the ROC curves of UCSS with SOFA (95% CI - 0.800 to 0.0808, P = 0.992), qSOFA (95% CI - 0.0611 to 0.0808, P = 0.409), and SIRS (95% CI - 0.0703 to 0.144, P = 0.502), finding that UCSS was non-inferior to these models. CONCLUSIONS: UCSS, a new convenient and cost-effective model, can predict septic shock following PCNL and provide more accurate discriminative and corrective capability than existing models by including only objective data. The predictive value of UCSS for septic shock after PCNL was greater than that of qSOFA or SIRS scores.

Oxalate-induced apoptosis through ERS-ROS-NF-κB signalling pathway in renal tubular epithelial cell.

BACKGROUND: Kidney stones are composed of approximately 70-80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms. METHODS: We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways. RESULTS: We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited. CONCLUSION: Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.

A dissolved inorganic carbon measurement method featuring self-calibration function via an electrodialytic generator.

A simple dissolved inorganic carbon (DIC) measurement method featuring self-calibration function via an electrodialytic bicarbonate eluent generator (cEDG) is described. It is based on gas diffusion flow analysis system that uses conductometric detection for sensing the resultant conductivity changes of the effluent caused by CO2 penetration. The standard carbon sources with concentration ranging from 0.1 to 6 mM produced online by cEDG are for DIC calibration, eliminating manual preparation.

Performance of SOFA, qSOFA and SIRS to predict septic shock after percutaneous nephrolithotomy.

OBJECTIVE: The new clinical criteria termed SOFA and qSOFA were demonstrated to be more accurate than SIRS in screening patients at high risk of sepsis. We aim to evaluate the ability of SOFA, qSOFA and SIRS to predict septic shock after PCNL. PATIENTS AND METHODS: Consecutive patients undergoing PCNL were included to assess the performance of SOFA, qSOFA and SIRS in predicting septic shock, the AUC of ROC curve and decision curve analysis were used, and the optimal cutoff values and their achieving time were calculated. RESULTS: Of the 431 included patients, 12 (2.7%) cases developed septic shock. Compared with non-septic shock patients, patients with septic shock were more likely to be female, have positive history of urine culture and higher urine leukocyte count, and show increased postoperative serum creatinine, PCT and decreased leukocyte. The optimal cutoff of SOFA, qSOFA and SIRS was > 2, > 0 and > 1, respectively. All of the 12 patients with verified septic shock met SOFA and SIRS criteria, while only 11 cases met qSOFA criterion. SOFA had the identical highest sensitivity (100%) and greater specificity (87% vs. 81%) than SIRS. qSOFA had higher specificity (92%) than both SOFA and SIRS at the expense of lower sensitivity (92%). The AUC of SOFA (0.973) to predict septic shock was greater than that of qSOFA (0.928) and SIRS (0.935). When combined with SIRS, SOFA outperformed qSOFA for discrimination of septic shock (AUC 0.987 vs. 0.978). Decision curve analysis indicated SOFA was clearly superior to both qSOFA and SIRS with a higher net benefit and net reduction in intervention. The qSOFA achieved the best time-based predictive efficiency, with the shortest median time to meet its cutoff, followed by SOFA and SIRS. CONCLUSION: The performance of SOFA in predicting septic shock after PCNL was slightly greater than qSOFA and SIRS. The comprehensive application of various criteria is recommended to assist early detection of septic shock following PCNL.

The characteristics and risk factors of healthcare-seeking men with lower urinary tract symptoms in China: Initial report from the POInT group.

AIMS: To investigate the clinical characteristics of health care-seeking men presenting with lower urinary tract symptoms (LUTS) in China and to reveal risk factors for symptom severity. METHODS: This multicenter, hospital-based, cross-sectional study recruited 1477 eligible male subjects, who were at least 45 years, seeking health care at 9 participating hospitals across the mainland China. The general medical information and subjective symptoms were recorded, followed by the measurement of prostate volume, urodynamic indices, and laboratory tests for kidney function, plus glucose/lipid metabolism. Univariate and multivariate linear regression were employed for the detection of risk factors for symptom severity. RESULTS: The proportion of mild, moderate, and severe LUTS was 14.6%, 32.6%, and 52.8%, respectively, with 62.2% reporting the triple combination of storage, voiding, and postmicturition symptoms. Median prostate volume was 44.6 ml, and 71.1% were experiencing comorbidities. Thirteen independent risk factors for LUTS severity were identified, namely, nocturnal voiding episodes and the presence of straining and weak steam; the triple combination of symptom subtypes; general and nocturia quality of life; Qmax and bladder outlet obstruction index; and numbers of comorbidities, hypertension, estimated glomerular filtration rate, and cholesterol and glycosylated hemoglobin. CONCLUSIONS: The majority of health care-seeking LUTS men present with moderate-to-severe and overlapping symptoms, with a high prevalence of both lower urinary tract dysfunction and systemic comorbidities. The evidence from both urological and nonurological independent risk factors demonstrate the multifactorial nature of LUTS, for which a multidisciplinary management is essential.

Risk factors for sepsis in patients with struvite stones following percutaneous nephrolithotomy.

PURPOSE: To describe the clinical characteristics of struvite stones and determine the preoperative predictors of sepsis in struvite patients undergoing percutaneous nephrolithotomy (PCNL). METHODS: A retrospective study of patients who underwent PCNL between April 2011 and March 2018 was performed. The data of the struvite stones and non-struvite stones groups were compared following propensity score matching. Subsequently, the struvite stones group was sub-divided for further analysis according to the Sepsis-3 definition: non-sepsis and sepsis groups. RESULTS: After matching based on age, gender, BMI, and number of access tracts, the comparative analysis showed that staghorn calculi and higher Guy's stone score were more frequently observed in non-struvite stone patients (n = 97), while a history of urolithiasis surgery (56.70%), preoperative broad-spectrum antibiotic therapy (53.61%), positive preoperative urine culture (55.67%), and sepsis (35.05%) after surgery were more common in patients (n = 97) with struvite stones (all P values < 0.05). Eighteen (18.56%) patients presented with multidrug-resistant (MDR) bacteriuria. Multivariate analysis demonstrated that the preoperative presence of MDR bacteriuria (OR = 3.203; P = 0.043) and increased serum creatinine (OR = 3.963; P = 0.010) were independent risk predictors of sepsis. The two factors were used to construct a nomogram to predict the probability of sepsis. The nomogram was well calibrated and had moderate discriminative ability (concordance index: 0.711). CONCLUSION: Our study revealed that patients with struvite stones were associated with a significantly high risk of calculi recurrence and sepsis after surgery. The presence of MDR bacteriuria preoperatively was a reliable factor to predict sepsis.

Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway.

BACKGROUND: The morbidity of nephrolithiasis is 2-3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. MATERIALS AND METHODS: We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. RESULTS: Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. CONCLUSION: Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.

Association of sirtuin 1 gene polymorphisms with nephrolithiasis in Eastern chinese population.

Sirtuin 1 (SIRT1), an NAD+-dependent deacylase, has been identified to be associated with renal tubular inflammatory conditions and metabolic disorders, which are risk factors of nephrolithiasis. To further confirm the role of the SIRT1 in kidney stone formation, the expression of SIRT1 was analyzed based on a mouse model and the genetic polymorphisms of SIRT1 gene was compared between patients with kidney stones and controls. The calcium oxalate (CaOx) crystal-induced renal injury model was established to analyzed the expression of SIRT1 in the kidney tissue of both wild-type and ApoE(-/-) mice. And a total of 430 Eastern Chinese subjects (215 patients with nephrolithiasis and 215 age- and gender-matched controls) were recruited for the present study to investigate the associations between 6 common single nucleotide polymorphisms (SNPs) (i.e., rs10509291, rs3740051, rs932658, rs33957861, rs3818292 and rs1467568) in the SIRT1 gene and the incidence of kidney stones. Pairwise linkage disequilibrium and the haplotypes of the 6 SNPs were also analyzed. The genotypes of SIRT1 gene polymorphisms were analyzed by a Snapshot assay. Reduced expression of SIRT1 was observed in the kidney of the mice in the crystal group, revealing the potential role of SIRT1 in the nephrolithiasis. However, we did not find a significant association between the 6 SNPs of the SIRT1 gene and kidney stone formation in the Eastern Chinese population.

Renal function changes after percutaneous nephrolithotomy in patients with renal calculi with a solitary kidney compared to bilateral kidneys.

OBJECTIVE: To evaluate renal function changes and risk factors for acute kidney injury (AKI) after percutaneous nephrolithotomy (PCNL) in patients with renal calculi with a solitary kidney (SK) or normal bilateral kidneys (BKs). PATIENTS AND METHODS: Between 2012 and 2016, 859 patients undergoing PCNL were retrospectively reviewed at Changhai Hospital. In all, 53 patients with a SK were paired with 53 patients with normal BKs via a propensity score-matched analysis. Data for the following variables were collected: age, sex, body mass index, stone size, distribution, operation time, perioperative outcomes, and complications. The complications were graded according to the modified Clavien-Dindo system. Univariable and multivariable logistic regression models were constructed to evaluate risk factors for predicting AKI. RESULTS: The SK and BKs groups were comparable in terms of age, sex ratio, stone size, stone location distribution, comorbidities, and American Society of Anesthesiologists Physical Status classification. The initial and final stone-free rates were comparable between the SK and BKs groups (initial: 52.83% vs 58.49%, P = 0.696; final: 84.91% vs 92.45%, P = 0.359). There was no difference between the two groups for complications, according to the Clavien-Dindo grades. The estimated glomerular filtration rate (eGFR) increased dramatically after the stone burden was immediately relieved, and during the 6-month follow-up eGFR was lower in the SK group compared with the BKs group. We found a modest improvement in renal function immediately after PCNL in the BKs group, and renal function gain was delayed in the SK group. Through logistic regression analysis, we discovered that a SK, preoperative creatinine and diabetes were independent risk factors for predicting AKI after PCNL. CONCLUSION: Considering the overall complication rates, PCNL is generally a safe procedure for treating renal calculi amongst patients with a SK or normal BKs. Follow-up renal function analysis showed a modest improvement in patients of both groups. Compared to patients with normal BKs, patients with a SK were more likely to develop AKI after PCNL.

Calyceal diverticulum mimicking simple parapelvic cyst: a case report.

Calyceal diverticulum is a cystic intrarenal cavity lined by nonsecretory transitional epithelium that communicates with the collecting system via a narrow isthmus or infundibulum. It is a rare anatomic anomaly with an incidence of 0.2% to 0.6% in the patients undergoing renal imaging.1 Single imaging modality usually cannot differentiate calyceal diverticulum from other cystic renal diseases.2 Here, we report a 60-year-old male who was reliably diagnosed with calyceal diverticulum by retrograde urography combined with non-enhanced computed tomography (CT) and magnetic resonance urography (MRU).

The effect of recasting by mothers with different conversational styles on the communication behavior of autistic children: Lag sequential analysis.

Recasting is the adult rephrasing of a child's immediately preceding utterance. It has been shown to have outstanding effects on promoting language development in autistic children. This study used lag sequential analysis to explore the impact of mothers' conversational styles on the communicative behavior of autistic children when using recasting. This study recruited 30 Chinese autistic children (aged 3-6 years) and their mothers. The utterances of the children and their mothers during 30-min interactions were transcribed, coded, and analyzed. The mothers' conversational styles were determined by the percentages of child-dominant, mother-dominant, and equality styles. The results indicated that mothers' conversational styles were predominantly child-dominant, differing from the expected mother-dominant style that is typical in Eastern cultures and traditions. However, some mothers still demonstrated a significant proportion of mother-dominant style in their conversation, while some exhibited a considerable amount of equality style. Moreover, mothers with a mainly child-dominant style and minimal use of mother-dominant and equality styles used recasting after the child's response, triggering the child to initiate new topics. Mothers with a child-dominant style combined with prominent mother-dominant features implemented untargeted self-recasting, the children did not respond significantly. Mothers with a child-dominant style combined with prominent equality features used recasting after the children responded, initiated, or expanded the conversation, which often facilitated the child's expansion of the conversation. These findings provide suggestions for designing parent-mediated early language interventions for autistic children.

A nitrogen-specific detector for high performance liquid chromatography.

We describe a nitrogen-specific detector (NSD) for aqueous mobile phase-based high performance liquid chromatography (HPLC). It is based by means of total hydrophilic organic nitrogen detection. Separated analytes are photooxidized online and converted to nitrate, followed by an ultravilet absorbance detector. It features response dependant on the product of nitrogen number in the molecule and its molar concentration, no matter what is ultravilet-absorbing or not. The HPLC equipped with NSD can quantify nitrogen-containing analytes via a sole standard of potassium nitrate for calibration. This results in identical calibration curve for all nitrogen-containing analytes, obviating individual calibration. The limit of detection of NSD is 4.3 µM N/L, and its linear range is up to 4 mM N/L.

Impacted anterior urethral calculus complicated by a stone-containing diverticulum in an elderly man: outcome of transurethral lithotripsy without resection of the diverticulum.

INTRODUCTION: The prevalence of lower urinary tract symptoms (LUTS) is about 20% in men aged 40 or above. Other than benign prostatic hyperplasia (BPH), urethral diverticulum or calculus is not uncommon for LUTS in men. Surgical treatment is often recommended for urethral diverticulum or calculus, but treatment for an impacted urethral calculus complicated by a stone-containing diverticulum is challenging. MATERIALS AND METHODS: An 82-year-old man had the persistence of LUTS despite having undergone transurethral resection of prostate for BPH. Regardless of treatment with broad spectrum antibiotics and an α-blocker, LUTS and post-void residual urine volume (100 mL) did not improve although repeated urinalysis showed reduction of WBCs from 100 to 10 per high power field. Further radiology revealed multiple urethral calculi and the stone configuration suggested the existence of a diverticulum. He was successfully treated without resecting the urethral diverticulum; and a new generation of ultrasound lithotripsy (EMS, Nyon, Switzerland) through a 22F offset rigid Storz nephroscope (Karl Storz, Tuttingen, Germany) was used to fragment the stones. RESULTS: The operative time was 30 minutes and the stones were cleanly removed. The patient was discharged after 48 hours with no immediate complications and free of LUTS during a 2 years follow-up. CONCLUSIONS: When the diverticulum is the result of a dilatation behind a calculus, removal of the calculus is all that is necessary. Compared with open surgery, ultrasound lithotripsy is less invasive with little harm to urethral mucosa; and more efficient as it absorbs stone fragments while crushing stones.

FDG PET/CT in a Case of Primary Angiosarcoma of the Kidney.

ABSTRACT: Primary angiosarcoma of the kidney is a rare aggressive malignancy. We describe MRI and FDG PET/CT findings in a case of primary renal angiosarcoma with hepatic, pulmonary, and bony metastases. The large primary tumor showed extensive necrosis and increased FDG uptake in the nonnecrotic components. Multiple metastatic lesions in the liver, lung, and bones were detected by FDG PET/CT. Most of the hepatic metastases seen on MRI were missed on FDG PET/CT due to low FDG avidity.

The Association Between Mother's Descriptive Language and Children with Autism's Conversational Repair: A Moderated Mediation Analysis.

This study tested the role of children with autism spectrum disorder (ASD)'s conversational expansion in mediating between mothers' descriptive language and children with ASD's conversational repair, and whether this mediation was moderated by the relative complexity of mother-child language. Videos of forty children with ASD engaging in various activities with their mothers were transcribed into language samples and then coded. Mediation analyses indicated that conversational expansion mediated the association between descriptive language and conversational repair. Moderated mediation analysis further indicated that the relative complexity of mother-child language moderated the relationship between descriptive language and conversational expansion, creating a conditional indirect effect. Although preliminary, the results of this study provide parents and practitioners with a new idea of language intervention strategies.

Stone Retropulsion Caused by the Pulse-Duration Adjustable Holmium Laser: Analysis of the Whole-Process Dynamics with a Modified Method.

Introduction: Stone retropulsion was shown to be impacted by pulse duration during holmium laser lithotripsy, although the whole process of retropulsion was troublesome to study. We developed a modified method to analyze retropulsion using a smartphone and video tracking software. Materials and Methods: A holmium laser system was incorporated with a short (200 µseconds) and long pulse-duration (LP) (800 µseconds), and a 272-µm core fiber was attached. A cross-sectional V-shaped rail was submerged in a tank, on which artificial stones were displaced linearly after lasering. Different combinations of pulse energy, frequency, and pulse duration were tested for at least 4 seconds. An iPhone 11 capable of high-definition videoing and video tracking software was used to analyze the stone's displacement and velocity. Results: For most settings, the displacement-time graph resembled logarithmic growth and the velocity peaked within the first second after lasering. Higher energy or frequency translated into greater displacement, accompanied by earlier and faster velocity peaks. When the laser power was constant, the short pulse-duration at the fourth second after lasering was much larger in 0.5 J × 40 Hz than 1.0 J × 20 Hz under the short pulse-duration (SP) (13.17 ± 0.92 mm vs 6.90 ± 1.98 mm, p < 0.05), but this discrepancy was offset by the LP. The largest stone displacement and velocity were observed in 0.5 J × 40 Hz SP. Conclusion: The pulse duration plays a dominant role in determining the stone retropulsion and velocity, and a long pulse decreases retropulsion and velocity. Given a constant power, the variable combination of frequency and pulse energy contributes to significantly different retropulsion with a short pulse rather than a long pulse. The modified method offers a feasible solution for the study of stone retropulsion by laser lithotripsy.

Inhibition of EZH2 ameliorates hyperoxaluria-induced kidney injury through the JNK/FoxO3a pathway.

AIMS: Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, has been shown to play a role in kidney diseases. However, its role in hyperoxaluria-induced renal tubular epithelial cells (TECs) injury remains unclear. MATERIALS AND METHODS: A hyperoxaluria rat model was established by providing 0.5% ammonium chloride and drinking water containing 1% ethylene glycol. TECs were exposed to oxalate stress. The 3-DZNeP, a selective EZH2 inhibitor, was administered in vivo and in vitro. Cell viability, ROS production, and apoptosis ratio were evaluated. Crystal deposition was detected by Von Kossa staining and kidney tissue injury was detected by HE staining and TUNEL. EZH2, H3K27me3, cleaved-caspase3, IL-6, and MCP-1 were examined by western blot or immunohistochemistry. KEY FINDINGS: Inhibition of EZH2 by 3-DZNeP significantly attenuated hyperoxaluria-induced oxidative and inflammatory injury and CaOx crystal deposition in vivo. Similarly, inhibition of EZH2 using 3-DZNeP or shRNA restored cell viability, suppressed LDH release and the production of intracellular ROS in vitro. Furthermore, the MAPK signaling pathway and FoxO3a levels were activated or elevated in TECs exposed to oxalate. EZH2 inhibition using 3-DZNeP blocked these effects. CC90003 (ERK inhibitor) or SB203580 (p38 inhibitor) did not significantly affect the expression of FoxO3a in TECs treated with 3-DZNeP and oxalate; only SP600125 (JNK inhibitor) significantly decreased FoxO3a expression. SIGNIFICANCE: EZH2 inhibition protects against oxalate-induced TECs injury and reduces CaOx crystal deposition in the kidney may by modulating the JNK/FoxO3a pathway; EZH2 may be a promising therapeutic target in TECs injury.

Gender-related differences in the performance of sequential organ failure assessment (SOFA) to predict septic shock after percutaneous nephrolithotomy.

The study aims to identify whether gender differences exist in the sequential organ failure assessment (SOFA) score to the extent of affecting its predictive accuracy for septic shock after percutaneous nephrolithotomy (PCNL). A retrospective study of 612 patients undergoing PCNL was performed. The SOFA scores of male and female groups were compared to identify any gender differences. The ROC curve was used to find differences between the original and adjusted SOFA scores. Postoperative septic shock developed in 21 (3.43%) cases. A marginally significant discrepancy in median SOFA scores between genders was discovered in a subgroup of patients < 40 years old (p = 0.048). A gender difference existed in the SOFA score after PCNL, with greater proportion of high scores in female patients (p = 0.011). Male patients had a higher proportion of ≥ 2 sub-score in hepatic and renal systems than female patients, caused by their higher preoperative bilirubin and creatinine (p < 0.05). An adjusted SOFA score was created to replace the original postoperative SOFA score with the perioperative changed values of bilirubin and creatinine. Performance of the adjusted SOFA score for predicting septic shock was comparable with the original SOFA score (AUC 0.987 vs. 0.985, p = 0.932). Under the premise of ensuring 100% sensitivity, the adjusted SOFA score reduced the 43.7% (31/71) false-positive rate for predicting septic shock compared with the original SOFA score. In conclusion, the gender should not be neglected when applying SOFA score for patients after PCNL. The adjusted SOFA score eliminates negative effects caused by gender differences in predicting septic shock.