International Alliance of Urolithiasis (IAU) guideline on staghorn calculi management.

BACKGROUND: The stone burden based management strategy reported in the guidelines published by different associations is well known for a long time. Staghorn calculi, representing the largest burden and most complex stones, is one of the most challenging cases to practicing urologists in clinical practice. The International Alliance of Urolithiasis (IAU) has released a series of guidelines on the management of urolithiasis. PURPOSE: To develop a series of recommendations for the contemporary management management of staghorn calculi and to provide a clinical framework for urologists treating patients with these complex stones. METHODS: A comprehensive literature search for articles published in English between 01/01/1976 and 31/12/2022 in the PubMed, OVID, Embase and Medline database is performed. A series of recommendations are developed and individually graded following the review of literature and panel discussion. RESULTS: The definition, pathogenesis, pathophysiology, preoperative evaluation, intraoperative treatment strategies and procedural advice, early postoperative management, follow up and prevention of stone recurrence are summarized in the present document. CONCLUSION: A series of recommendations regarding the management of staghorn calculi, along with related commentary and supporting documentation offered in the present guideline is intended to provide a clinical framework for the practicing urologists in the management of staghorn calculi.

Prediction of pathologic complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

Purpose: To investigate the predictive factors of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) patients who had been treated with neoadjuvant chemoradiation (nCRT). Methods and materials: For this retrospective study, 53 LARC patients (37 males and 16 females; age range 25 to 79 years) were selected. Clinical characteristics, baseline mrTNM staging, MR gross tumor volumes (GTV), and pCR were evaluated. The diagnostic accuracy of GTV for predicting pCR was calculated. Results: Among 53 LARC patients, 15 patients achieved pCR (28.3%), while 38 patients achieved non-pCR. Only three (5.7%) out of 53 patients did not downstage after nCRT. GTV and tumor differentiation were the significant prognostic parameters for predicting pCR. A tumor volume threshold of 21.1 cm3 was determined as a predictor for pCR, with a sensitivity of 84% and specificity of 47%. In addition, GTV was associated with mrN stage, circumferential resection margin (CRM) status, extramural vascular invasion (EMVI) status, and pretreatment serum CEA level. Conclusion: Tumor volume and tumor differentiation have significant predictive values in preoperative assessment of pCR among LARC patients. These findings aid clinicians to discriminate those patients who may likely benefit from preoperative regimens and to make optimal treatment plans.

Mechanism of Porphyra Yezoensis Polysaccharides in Inhibiting Hyperoxalate-Induced Renal Injury and Crystal Deposition.

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.

7.5F Mini Flexible Ureteroscope in Retrograde Intrarenal Surgery: Initial Results from a Multicenter Randomized Clinical Trail.

Objective: To report the initial results of an randomized clinical trail comparing the safety and efficacy between 7.5F and 9.2F flexible ureteroscope (FUS) in the management of renal calculi <2 cm. Materials and Methods: Eighty patients were enrolled and received retrograde intrarenal surgery (RIRS) with a different size FUS. The operation results and complications were compared. Results: Two cases in the 7.5F group and four cases in the 9.2F group failed to insert the 12/14F ureteral access sheath (UAS), respectively, and no significant difference (p = 0.396) was noted. However, 10/12F UAS was inserted in the 7.5F group, but not available in the 9.2F group, and thus, the 10/12F UAS inserting rate in the 7.5F group was higher than in the 9.2F group (100% vs 0%, p = 0.014), and the UAS insertion failure rate in 9.2F group was higher than in the 7.5F group (10% vs 0%, p = 0.040). The operation time in 7.5F group was shorter than the 9.2F group (35.60 ± 7.86 vs 41.05 ± 8.14, p = 0.003). Less irrigation was required in 7.5F group (813.93 ± 279.47 mL vs 1504.18 ± 385.31 mL, p = 0.000). The postoperative fever rate in 9.2F group was higher than 7.5F group (20% vs 5%, p = 0.043). There was no significant difference in sepsis (0% vs 2.5%, p = 0.314) between the two groups. No significant difference was noted in hospital stay (0.93 ± 0.49 days vs 1.14 ± 0.64 days, p = 0.099) between the two groups. The final stone-free rate (SFR) in 7.5F group was higher than 9.2F group (95% vs 80%, p = 0.043). Conclusion: The latest 7.5F mini FUS was a reliable instrument in RIRS to keep a good visualization with low requirement of irrigation, low postoperative infection complication, and also a high SFR when compared with the conventional 9.2F FUS. Clinical Trial Registration: NCT05231577.

Navigating Entire Collecting System During Supine Percutaneous Nephrolithotomy: Is Rigid Nephroscopy Enough? A Prospective Study by International Alliance of Urolithiasis Supine Percutaneous Nephrolithotomy Working Group.

Background: During percutaneous nephrolithotomy (PCNL), accessibility to the entire collecting system is crucial to check the presence of any residual stone fragments. In this study, we aimed to identify the rate of accessibility of all caliceal cavities using lower-, middle- and, upper-pole punctures and the eventual benefit of simultaneous utilization of retrograde/antegrade flexible nephroscopy. Materials and Methods: Data of patients undergone supine PCNL in five different institutions were collected prospectively. Access status to other poles of the kidney with a rigid nephroscope, antegrade access status to the other poles of the kidney with a flexible nephroscope, or retrograde access with a flexible ureterorenoscope were all evaluated together with detection of residual fragments. Access status to the other poles of the kidney with anterograde and retrograde approaches were compared. Results: Data of 226 patients were analyzed and stone-free status was achieved in 207 (91.6%) of the patients. The entire collecting system could be successfully approached by a rigid nephroscope in 50% of the cases through middle-pole puncture. This rate was significantly higher than that of lower-pole puncture (37.1%) and upper-pole puncture (28.1%) (P = .035). The successful approach to the entire collecting system with retrograde ureterorenoscopy was possible in 97.6% of the cases, while the successful approach was possible in 48 of the 60 cases (80%) with the retrograde approach (P < .0001). Conclusions: During PCNL, evaluation of the entire collecting system with rigid nephroscopy is not possible in a significant portion of the patients. We believe that the application of flexible nephroscopy, particularly via retrograde approach improves the stone-free rates.

First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Determining the optimal pharmacokinetic modelling and simplified quantification method of [18F]AlF-P16-093 for patients with primary prostate cancer (PPCa).

PURPOSE: This paper discusses the optimization of pharmacokinetic modelling and alternate simplified quantification method for [18F]AlF-P16-093, a novel tracer for in vivo imaging of prostate cancer. METHODS: Dynamic PET/CT scans were conducted on eight primary prostate cancer patients, followed by a whole-body scan at 60 min post-injection. Time-activity curves (TACs) were obtained by drawing volumes of interest for primary prostatic and metastatic lesions. Optimal kinetic modelling involved evaluating three compartmental models (1T2K, 2T3K, and 2T4K) accounting for fractional blood volume (Vb). The simplified quantification method was then determined based on the correlation between the static uptake measure and total distribution volume (Vt) obtained from the optimal pharmacokinetic analysis. RESULTS: In total, 17 intraprostatic lesions, 10 lymph nodes, and 36 osseous metastases were evaluated. Visually, the contrast of the tumor increased and showed the steepest incline within the first few minutes, whereas background activity decreased over time. Full pharmacokinetic analysis revealed that a reversible two-compartmental (2T4K) model is the preferred kinetic model for the given tracer. The kinetic parameters K1, k3, Vb, and Vt were all significantly higher in lesions when compared with normal tissue (P < 0.01). Several simplified protocols were tested for approximating comprehensive dynamic quantification in tumors, with image-based SURmean (the ratio of tumor SUVmean to blood SUVmean) within the 28-34 min window found to be sufficient for approximating the total distribution Vt values (R2 = 0.949, P < 0.01). Both Vt and SURmean correlated significantly with the total serum prostate-specific antigen (tPSA) levels (P < 0.01). CONCLUSIONS: This study introduced an optimized pharmacokinetic modelling approach and a simplified acquisition method for [18F]AlF-P16-093, a novel PSMA-targeted radioligand, highlighting the feasibility of utilizing one static PET imaging (between 30 and 60 min) for the diagnosis of prostate cancer. Note that the image-derived input function in this study may not reflect the true corrected plasma input function, therefore the interpretation of the associated kinetic parameter estimates should be done with caution.

LncRNA MAGI2-AS3 inhibites tumor progression by up-regulating STAM via interacting with miR-142-3p in clear cell renal cell carcinoma.

Revealing the role of non-coding RNAs (ncRNAs) in inducing dysregulated pathological responses to external signals may identify therapeutic targets for inhibiting the progression of clear cell renal cell carcinoma (ccRCC). Non-coding RNAs belong to a class of RNA molecules that do not encode proteins but possess diverse biological functions, playing essential roles in the occurrence and development of metastatic and proliferative tumors. To investigate the impact of the upstream interaction between miR-142-3p and lncRNA MAGI2-AS3 on the tumor-suppressive activity of the STAM gene, we firstly conducted bioinformatics analysis to predict the upstream miRNAs of STAM and the upstream lncRNAs of the miRNAs through online databases (miRanda, miRDB, TargetScan, LncBase v2), which were further validated by the starBasev2.0 database. Subsequently, multiple experimental techniques were employed to validate these findings, including RT-qPCR, Western blotting, measurement of cellular functional activity, and luciferase reporter assays. Through these experimental methods, we provided compelling evidence regarding the role of miR-142-3p and MAGI2-AS3 in regulating STAM gene expression and functionality, revealing their potential significance in tumor suppression. Our research demonstrates the importance of the MAGI2-AS3/miR-142-3p/STAM signaling pathway axis in ccRCC. MAGI2-AS3 competes for binding with miR-142-3p, resulting in upregulated STAM gene expression. This upregulation inhibits tumor proliferation and metastasis in ccRCC cells. Conversely, overexpression of miR-142-3p or silencing of MAGI2-AS3 promotes tumor behavior, while downregulation of miR-142-3p inhibits the development of ccRCC. Targeting the MAGI2-AS3/miR-142-3p/STAM axis holds promise as a therapeutic strategy for ccRCC treatment.

Drivers and decoupling analysis of carbon emissions in the non-ferrous metal industry-evidence from 28 provinces in China.

Emissions from the non-ferrous metal industry are a major source of carbon emissions in China. Understanding the decoupling of carbon emissions from the non-ferrous metal industry and its influencing factors is crucial for China to achieve its "double carbon" goal. Here, we applied the Tapio decoupling model to measure the decoupling status and developmental trends of carbon output and emissions of the non-ferrous metal industry in China. The panel interaction fixed effects model is used to empirically analyze the influencing factors of carbon emissions in China's non-ferrous metal industry. The results show that carbon emissions from China's non-ferrous metal industry have experienced three main states: strong decoupling, growth connection, and negative growth decoupling. The carbon emissions of the non-ferrous metal industry in some eastern and central provinces from 2000 to 2004 were in a negative decoupling state. Most provinces in the western and central regions were either in a strong or weak decoupling state based on the developmental trend of the decoupling state of carbon emissions. However, from 2015 to 2019, the decoupling status of carbon emissions in most provinces in western and central China had a significantly negative, weakly negative, or a negative growth decoupling status. Energy structure, energy intensity, cost, and non-ferrous metal production all have a positive driving effect on carbon emissions in the non-ferrous metal industry. Production had a mitigating effect on carbon emissions in the non-ferrous metal industry between 2010-2014 in the eastern region of China. From the results of our study, we propose policy recommendations to promote a strong decoupling of carbon emissions from the non-ferrous metal industry by improving energy structure, reducing energy intensity, and optimizing production capacity.

Estimation of peer effect in university students' employment intentions: randomization evidence from China.

As a key determinant of employment behavior, employment intention is easily affected by the environment, others and their subconsciousness, thus deviating from the optimal decision predicted by the classical economic model. Peers are an important environmental factor that directly affects individual behavior, but their effect on employment intentions has not been fully verified. The paper analyzes the class peer effect on university students' employment intentions using random class assignment data from a central province in China. It is found that positive peer employment behavior has a significant positive effect on university students' employment intentions, and this result remains robust after replacing the proxy variables. Further analysis of the peer effect mechanism reveals that the provision and dissemination of school employment information enhances the peer effect in employment intentions, while the help given by parents and family background weakens the peer effect. The results of the dose effect of the peer effect show that the peer effect tends to increase over time.

Predictive value of single-nucleotide polymorphism signature for nephrolithiasis recurrence: a 5-year prospective study.

Background: Genetic variations are linked to kidney stone formation. However, the association of single nucleotide polymorphism (SNPs) and stone recurrence has not been well studied. This study aims to identify genetic variants associated with kidney stone recurrences and to construct a predictive nomogram model using SNPs and clinical features to predict the recurrence risk of kidney stones. Methods: We genotyped 49 SNPs in 1001 patients who received surgical stone removal between Jan 1 and Dec 31 of 2012. All patients were confirmed stone-free by CT scan and then received follow-up at least 5 years. SNP associations with stone recurrence were analyzed by Cox proportion hazard model. A predictive nomogram model using SNPs and clinical features to predict the recurrence risk of kidney stones was developed by use of LASSO Cox regression. Results: The recurrence rate at 3, 5, 7 years were 46.8%, 71.2%, and 78.4%, respectively. 5 SNPs were identified that had association with kidney stone recurrence risk. We used computer-generated random numbers to assign 500 of these patients to the training cohort and 501 patients to the validation cohort. A nomogram that combined the 14-SNPs-based classifier with the clinical risk factors was constructed. The areas under the curve (AUCs) at 3, 5 and 7 years of this nomogram was 0.645, 0.723, and 0.75 in training cohort, and was 0.631, 0.708, and 0.727 in validation cohort, respectively. Results show that the nomogram presented a higher predictive accuracy than those of the SNP classifier or clinical factors alone. Conclusion: SNPs are significantly associated with kidney stone recurrence and should add prognostic value to the traditional clinical risk factors used to assess the kidney stone recurrence. A nomogram using clinical and genetic variables to predict kidney stone recurrence has revealed its potential in the future as an assessment tool during the follow-up of kidney stone patients.

KDM3B Single-Nucleotide Polymorphisms Impact Radiation Therapy Toxicity Through Circular RNA-Mediated KDM3B Expression and Inflammatory Responses.

PURPOSE: Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) associated with radiation therapy (RT) toxicities in patients with prostate cancer. SNP rs17599026 in intron 21 of KDM3B is significantly associated with the development of late urinary toxicity, specifically in the increase in urinary frequency 2 years after RT compared with pretreatment conditions. The present study aimed to provide mechanistic insights for this association. METHODS AND MATERIALS: Using human tissues and cell lines, we examined the protein expression of KDM3B and molecular mechanisms underlying the SNP modulation by variants of KDM3B SNP alleles. In animals with normal and heterozygous expressions of Kdm3b, we examined the relationship between Kdm3b expression and radiation toxicity. RESULTS: KDM3B rs17599026 lies in a motif important for circular RNA expression that is responsible for sponging miRNAs to regulate KDM3B expression. Using a murine model with heterozygous deletion of the Kdm3b gene, we found that lower Kdm3b expression is associated with altered pattern of urination after bladder irradiation, which is related to differential degrees of tissue inflammation as measured by analyses of gene expression, lymphocyte infiltration, and noninvasive ultrasound imaging. CONCLUSIONS: KDM3B SNPs can impact its expression through regulating noncoding RNA expression. Differential KDM3B expression underlies radiation toxicity through tissue inflammation at the molecular and physiological level. Our study outcome offers a foundation for mechanism-based mitigation for radiation toxicity for prostate cancer survivors.

A new histone deacetylase inhibitor remodels the tumor microenvironment by deletion of polymorphonuclear myeloid-derived suppressor cells and sensitizes prostate cancer to immunotherapy.

BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed in men. Immune checkpoint blockade (ICB) alone showed disappointing results in PCa. It is partly due to the formation of immunosuppressive tumor microenvironment (TME) could not be reversed effectively by ICB alone. METHODS: We used PCa cell lines to evaluate the combined effects of CN133 and anti-PD-1 in the subcutaneous and osseous PCa mice models, as well as the underlying mechanisms. RESULTS: We found that CN133 could reduce the infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), and CN133 combination with anti-PD-1 could augment antitumor effects in the subcutaneous PCa of allograft models. However, anti-PD-1 combination with CN133 failed to elicit an anti-tumor response to the bone metastatic PCa mice. Mechanistically, CN133 could inhibit the infiltration of PMN-MDSCs in the TME of soft tissues by downregulation gene expression of PMN-MDSC recruitment but not change the gene expression involved in PMN-MDSC activation in the CN133 and anti-PD-1 co-treatment group relative to the anti-PD-1 alone in the bone metastatic mice model. CONCLUSIONS: Taken together, our work firstly demonstrated that combination of CN133 with anti-PD-1 therapy may increase the therapeutic efficacy to PCa by reactivation of the positive immune microenvironment in the TME of soft tissue PCa.

Industrial agglomeration, spatial structure and economic growth: Evidence from urban cluster in China.

The industrial agglomeration and spatial structure characteristics play important roles in the economic development and improvement of competitiveness for urban cluster. The article constructs a C-D model using panel data of 130 cities in 13 urban clusters in China from 2006 to 2015, then constructs regression equations of the relationship between industrial agglomeration, spatial structure and economic growth through fixed-effects regression models, and finally analyzes the influence of industrial agglomeration and spatial structure on economic growth of urban clusters. The research results indicate that the economic structure of urban clusters is affected by both the level of industrial agglomeration and spatial structure of urban clusters. The higher the level of industrial agglomeration, the more obvious the economic effect of urban clusters. From the perspective of the spatial structure of urban clusters, the impact of monocentric spatial structure of urban clusters on economic growth shows a positive correlation. Human capital, physical capital, economic openness and resident population have significant positive effects on the economic growth of urban clusters, while transportation infrastructure is not significant. At this moment, we should further promote the industrial agglomeration, and continuously optimize the internal spatial structure of urban clusters with the linkage mechanism of land and household registration to improve the comprehensive competitiveness of urban clusters.

Miniaturization in percutaneous nephrolithotomy: What is new?

Objective: To summarize recent advancements in mini-percutaneous nephrolithotomy (mini-PCNL) in surgical technique, stone removal strategy, lithotripsy, and surgical model from the current literature. Methods: We conducted a narrative review of relevant English-language articles up to October 2022 using the PubMed and Web of Science databases. The following keywords were used in the search: "percutaneous nephrolithotomy", "minimally invasive percutaneous nephrolithotomy", "mini-PCNL", "mini-perc", "mPCNL", and "miniaturization". Results: A series of new progress has been made in many aspects of mini-PCNL, such as further reduction of tract size-needle perc and further improvement of robotic-assisted PCNL-artificial intelligence-powered robotic devices. Conclusion: Many studies and trials have been conducted to reduce morbidity and increase the safety and effectiveness of mini-PCNL. It is crucial to realize that miniaturization of PCNL requires not only a smaller percutaneous tract size, but also an adjustment strategically in renal access, stone removal, lithotripsy, and surgical model in general. More large-scale prospective research needs to be carried out to further validate and optimize the safety and effectiveness of mini-PCNL.