TFE3-SLC36A1 axis promotes resistance to glucose starvation in kidney cancer cells.

Higher demand for nutrients including glucose is characteristic of cancer. "Starving cancer" has been pursued to curb tumor progression. An intriguing regime is to inhibit glucose transporter GLUT1 in cancer cells. In addition, during cancer progression, cancer cells may suffer from insufficient glucose supply. Yet, cancer cells can somehow tolerate glucose starvation. Uncovering the underlying mechanisms shall shed insight into cancer progression and benefit cancer therapy. TFE3 is a transcription factor known to activate autophagic genes. Physiological TFE3 activity is regulated by phosphorylation-triggered translocation responsive to nutrient status. We recently reported TFE3 constitutively localizes to the cell nucleus and promotes cell proliferation in kidney cancer even under nutrient replete condition. It remains unclear whether and how TFE3 responds to glucose starvation. In this study, we show TFE3 promotes kidney cancer cell resistance to glucose starvation by exposing cells to physiologically relevant glucose concentration. We find glucose starvation triggers TFE3 protein stabilization through increasing its O-GlcNAcylation. Furthermore, through an unbiased functional genomic study, we identify SLC36A1, a lysosomal amino acid transporter, as a TFE3 target gene sensitive to TFE3 protein level. We find SLC36A1 is overexpressed in kidney cancer, which promotes mTOR activity and kidney cancer cell proliferation. Importantly, SLC36A1 level is induced by glucose starvation through TFE3, which enhances cellular resistance to glucose starvation. Suppressing TFE3 or SLC36A1 significantly increases cellular sensitivity to GLUT1 inhibitor in kidney cancer cells. Collectively, we uncover a functional TFE3-SLC36A1 axis that responds to glucose starvation and enhances starvation tolerance in kidney cancer.

Management of renal sinus angiomyolipoma: modified robotic nephron-sparing surgery in a single center.

BACKGROUND: Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of robotic nephron-sparing surgery (NSS) for treating RSAML. METHODS: We retrospectively evaluated 15 patients with RSAMLs who were treated with robotic NSS at the Department of Urology of Tongji hospital, ranging from November 2018 to September 2022. Renal vessels and ureter were dissected. The outer part of RSAML was resected. The rest of tumor was removed by bluntly grasp, curettage and suction. Absorbable gelatin sponges were filled in the renal sinus. The preoperative parameters, operative measures and postoperative outcomes were all collected. Follow-up was performed by ultrasonography and estimated glomerular filtration rate (eGFR). RESULTS: Robotic NSS was successfully performed in all the patients, without any conversion to open surgery or nephrectomy. The mean operation time was 134.13 ± 40.56 min. The mean warm ischemia time was 25.73 ± 3.28 min. The median estimated blood loss was 100 [50, 270] ml and 1 patient required blood transfusion. The mean drainage duration was 5.77 ± 1.98 days. The median postoperative hospital stay was 6.90 [5.80, 8.70] days. Two patients experienced postoperative urinary tract infection (Clavien-Dindo Grade II). During the median follow-up of 25.53 ± 15.28 months, patients received 91.18% renal function preservation. No local recurrence occurred in all the patients. CONCLUSIONS: Robotic NSS for RSAML is a complicated procedure that demands technical expertise and a well-designed strategy is critical in the operation. Treating RSAML with modified robotic NSS is safe, effective and feasible.

Tryptophan metabolism induced by TDO2 promotes prostatic cancer chemotherapy resistance in a AhR/c-Myc dependent manner.

BACKGROUND: Tumor cells exhibit enhanced metabolism of nutrients to satisfy the demand of sustained proliferation in vivo. Seminal reports have presented evidence that tryptophan (Trp) metabolic reprogramming induced by aberrant indoleamine 2,3-dioxygenases could promote tumor development in several cancer types. However, the underlying mechanism of Trp metabolism associated tumor progression is not fully understood. MATERIALS AND METHODS: Prostatic cell lines LNCaP and VCaP were purchased from the Cell Bank of the Chinese Academy of Sciences (China). Human prostatic tumor tissue samples were obtained from the Tongji Hospital. Female NOD-SCID mice (6 ~ 8 weeks) were purchased from Huafukang Co. (China) and raised in SPF room. Commercial kits and instruments were used for cell apoptosis analysis, real-time PCR, western blotting, ELISA analysis and other experiments. RESULT: Comparing the tumor tissues from prostatic cancer patients, we found elevated expression of tryptophan 2, 3-dioxygenase 2 (TDO2), and elevated Trp metabolism in chemo-resistant tumor tissues. In vitro, overexpression of TDO2 significantly promoted the Trp metabolism in prostatic cancer cell lines LNCaP and VCap, resulting in the multidrug resistance development. Mechanistically, we demonstrated that Trp metabolite kynurenine (Kyn) promoted the upregulation and nuclear translocation of transcription factor aryl hydrocarbon receptor (AhR). Subsequently, AhR collaborated with NF-κB to facilitate the activation of c-Myc. In turn, c-Myc promoted the up-regulation of ATP-binding cassette (ABC) transporters and Trp transporters, thereby contributing to chemoresistance and strengthened Trp metabolism in prostatic cancer. Interrupt of Trp/TDO2/Kyn/AhR/c-Myc loop with c-Myc inhibitor Mycro-3 efficiently suppressed the chemoresistance and improved the outcome of chemotherapy, which described a new strategy in clinical prostatic cancer treatment. CONCLUSION: Our study demonstrates that elevated TOD2 expression promoted Trp metabolism and metabolite Kyn production, thus resulting in the activation of AhR/c-Myc/ABC-SLC transporters signaling pathway. Interrupt of Trp metabolism/c-Myc loop efficiently suppressed the drugs resistance induced by TDO2, which represented potential target to improve the outcome in drug-resistant prostatic cancer treatment.

Intelligent Mining of Urban Ventilation Corridors Based on High-Precision Oblique Photographic Images.

With the advancement of urbanization and the impact of industrial pollution, the issue of urban ventilation has attracted increasing attention. Research on urban ventilation corridors is a hotspot in the field of urban planning. Traditional studies on ventilation corridors mostly focus on qualitative or simulated research on urban climate issues such as the intensified urban heat island effect, serious environmental pollution, and insufficient climate adaptability. Based on the high-precision urban remote sensing image data obtained by aeromagnetic oblique photography, this paper calculates the frontal area density of the city with reference to the urban wind statistics. Based on the existing urban patterns, template matching technology was used to automatically excavate urban ventilation corridors, which provides scientific and reasonable algorithmic support for the rapid construction of potential urban ventilation corridor paths. It also provides technical methods and decision basis for low-carbon urban planning, ecological planning and microclimate optimization design. This method was proved to be effective through experiments in Deqing city, Zhejiang Province, China.

Initial Experience with Hybrid Partial Nephrectomy with Ultrasound-guided Balloon Catheter Occlusion of the Renal Artery for Recurrent Renal Tumors.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

A Novel Predictive Model of Pathological Lymph Node Metastasis Constructed with Preoperative Independent Predictors in Patients with Renal Cell Carcinoma.

Introduction: Renal cell carcinoma (RCC) is one of the most common urinary tumors. The risk of metastasis for patients with RCC is about 1/3, among which 30−40% have lymph node metastasis, and the existence of lymph node metastasis will greatly reduce the survival rate of patients. However, the necessity of lymph node dissection is still controversial at present. Therefore, a new predictive model is urgently needed to judge the risk of lymph node metastasis and guide clinical decision making before operation. Method: We retrospectively collected the data of 189 patients who underwent retroperitoneal lymph node dissection or enlarged lymph node resection due to suspected lymph node metastasis or enlarged lymph nodes found during an operation in Tongji Hospital from January 2016 to October 2021. Univariate and multivariate logistic regression and least absolute shrinkage and selection operator (lasso) regression analyses were used to identify preoperative predictors of pathological lymph node positivity. A nomogram was established to predict the probability of lymph node metastasis in patients with RCC before surgery according to the above independent predictors, and its efficacy was evaluated with a calibration curve and a DCA analysis. Result: Among the 189 patients, 54 (28.60%) were pN1 patients, and 135 (71.40%) were pN0 patients. Three independent impact factors were, finally, identified, which were the following: age (OR = 0.3769, 95% CI = 0.1864−0.7622, p < 0.01), lymph node size according to pre-operative imaging (10−20 mm: OR = 15.0040, 95% CI = 1.5666−143.7000, p < 0.05; >20 mm: OR = 4.4013, 95% CI = 1.4892−7.3134, p < 0.01) and clinical T stage (cT1−2 vs. cT3−4) (OR = 3.1641, 95% CI = 1.0336−9.6860, p < 0.05). The calibration curve and DCA (Decision Curve Analysis) showed the nomogram of this predictive model had good fitting. Conclusions: Low age, large lymph node size in pre-operative imaging and high clinical T stage can be used as independent predictive factors of pathological lymph node metastasis in patients with RCC. Our predictive nomogram using these factors exhibited excellent discrimination and calibration.

Role of Nox4 in High Calcium-Induced Renal Oxidative Stress Damage and Crystal Deposition.

Aims: We aimed at exploring the role of nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (Nox4) in the regulation of hypercalciuria-induced renal oxidative damage and crystal depositions. Results: High calcium activated Nox4 expression through protein kinase C (PKC). Downregulation of Nox4 expression attenuated hypercalciuria-induced osteoblast-associated protein expression, oxidative stress injury, and crystal deposition in rat kidneys of 1,25-dihydroxyvitamin D3 (VitD) urolithiasis model. Further, calcium-induced activation of mitogen-activated protein kinase (MAPK), overexpression of osteoblast-associated protein, oxidative stress injury, apoptosis, and calcium salt deposition in normal rat kidney epithelial-like (NRK-52E) cells were reversed by downregulating Nox4 expression but were enhanced by upregulating Nox4 expression in vitro. Moreover, calcium-induced increases of osteoblast-associated protein expression were attenuated by the c-Jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) inhibitors. Innovation: Our results demonstrated the effect of Nox4 in the pathological process of kidney stones in in vitro and in vivo studies for the first time. Calcium aggravates renal oxidative stress injury and crystal deposition by activating the Nox4-related reactive oxygen species (ROS)-ERK/JNK pathway in the rat kidney. This study is expected to provide a new theoretical basis for the prevention and treatment of kidney stones. Conclusion: Nox4-derived ROS induced by calcium through PKC caused oxidative stress damage and apoptosis in renal tubular epithelial cells; in addition, Nox4-derived ROS induced by calcium mediated abnormal activation of the bone morphogenetic protein 2 (BMP2) signaling pathway through the MAPK signaling pathway, which induced renal tubular epithelial cells to transdifferentiate into osteoblast-like cells, resulting in the formation of a kidney stone. Antioxid. Redox Signal. 36, 15-38.

Statin Use and the Risk of Prostate Cancer Biochemical Recurrence Following Definitive Therapy: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Numerous studies have reported the role of statins on biochemical recurrence (BCR) among patients with prostate cancer (PCa) after definite treatment. However, the conclusions of these studies are contradictory. We aimed to determine the effect of statins on BCR of PCa using a systematic review and meta-analysis. Methods: We searched PubMed (Medline) and other databases for cohort studies evaluating the effect of statins on the BCR of patients with PCa between January 1, 2000, and December 31, 2021. The random effects (RE) model and quality effects (QE) model were used to calculate the pooled hazard ratio (pHR) and pooled risk ratio (pRR) and their 95% confidence interval (95% CI). Results: A total of 33 cohort studies were finally selected and included in this systematic review and meta-analysis. Statin use was significantly associated with a 14% reduction in the HR of BCR (pHR: 0.86, 95% CI: 0.78 to 0.95, I2 = 64%, random effects model, 31 studies) and a 26% reduction in the RR of BCR (pRR: 0.74, 95% CI: 0.57 to 0.94, 24,591 patients, I2 = 88%, random effects model, 15 studies) among patients with PCa. The subgroup analyses showed that statins could result in 22% reduction in the HR of BCR (pHR: 0.78, 95% CI: 0.61 to 0.98, I2 = 57%, random effects model) among patients accepting radiotherapy (RT). Conclusions: Our study suggests that statins have a unique role in the reduction of BCR in patients with PCa after definite treatment, especially RT. In the future, more clinical trials and in vitro and animal experiments are needed to further verify the effects of statins in PCa and the potential mechanisms.

A Four-Cell-Senescence-Regulator-Gene Prognostic Index Verified by Genome-Wide CRISPR Can Depict the Tumor Microenvironment and Guide Clinical Treatment of Bladder Cancer.

Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan-Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa.

Research on Learning Evaluation of Online General Education Course Based on BP Neural Network.

Network open curriculum provides a new solution for general education in local colleges and universities, which makes the network curriculum widely popularized and applied in colleges and universities. However, due to the lack of good curriculum learning evaluation, it is inconvenient for learners to choose. Therefore, this paper proposes to use the BP neural network model to evaluate the learning process of network general education course. Based on the course and user data provided by the existing platform, this paper constructs an online course learning evaluation model and studies the structure and effect relationship among learning experience, learning investment, and learning performance of ordinary online courses based on the preaging process product (3P) model and structural analysis method. Our research shows that curriculum quality is a key factor in analyzing and predicting learning results, which has a great impact on learning achievement. Learning experience is a direct factor affecting academic achievement. Learning experience, as an intermediary variable, indirectly affects e-learning performance. At the same time, it puts forward some suggestions to optimize the learning effect of ordinary online courses. On the one hand, the evaluation model provided in this paper can provide a reference for learners to select online courses; on the other hand, it can also be used as a supplement to the existing subjective evaluation model.

Tumor-Associated Macrophage Promotes the Survival of Cancer Cells upon Docetaxel Chemotherapy via the CSF1/CSF1R-CXCL12/CXCR4 Axis in Castration-Resistant Prostate Cancer.

Castration-resistant prostate cancer (CRPC) is an advanced stage of prostate cancer that can progress rapidly even in patients treated with castration. Previously, we found that tumor-associated macrophages (TAM) can be recruited by CSF-1 secreted by docetaxel-treated prostate cancer cells and promote the survival of cancer cells in response to chemotherapy. The inhibition of CSF-1R can impede this effect and significantly prolong survival in xenograft mice. However, the actual mechanism of how TAM improves cancer cell survival still remains elusive and controversial. Here, for the first time, we found that the enhanced survival of cancer cells achieved by TAM was mainly mediated by CXCR4 activation from the increased secretion of CXCL12 from CSF-1 activated TAM. This finding helps to clarify the mechanism of chemoresistance for second-line chemotherapy using docetaxel, facilitating the development of novel drugs to overcome immune tolerance in castration-resistant prostate cancer.

Robot-assisted Laparoscopic Pyeloplasty in Adults: A Comparison Analysis of Primary versus Redo Pyeloplasty in a Single Center.

PURPOSE: Approximately 10% of all primary pyeloplasties will require at least one secondary intervention. Our aim was to analyze whether secondary repair will pose additional challenges during robotic pyeloplasty compared with the primary pyeloplasty. MATERIAL AND METHODS: 114 patients who underwent robot-assisted laparoscopic pyeloplasty (RALP) between February 2015 and August 2018 were retrospectively reviewed. Patients were divided into; primary and secondary repair. The demographics, intraoperative parameters, postoperative parameters, and success rate of these two groups were collected and compared. Primary RALP data were further stratified into those who previously underwent ipsilateral endourological surgeries (IES) at the obstruction site and those who did not, to evaluate the effect of IES has on the outcome of RALP. Success was defined as symptomatic and radiological relief. RESULTS: Of the 114 patients, five complicated cases (three horseshoe kidneys, one duplicated system, and one retrocaval ureter) were excluded from the comparison. The remaining 96 primary and 13 secondary repairs were compared. Intraoperative and postoperative parameters showed no significant difference between the two groups. The results of 99 patients (87 vs. 12 in primary vs. secondary, respectively) were available after 27.5 months mean follow-up. The overall success was 92%, 8 patients failed (5 vs. 3 in primary vs. secondary, respectively) and required further surgical interventions. CONCLUSION: Though surgically challenging with increased recurrence rates according to the literature we reviewed. However, our data failed to show any significant difference between the primary and redo RALP perhaps due to the smaller size in the redo RALP group.

Management of recurrent ureteral stricture: a retrospectively comparative study with robot-assisted laparoscopic surgery versus open approach.

BACKGROUND: Management of recurrent ureteral stricture is challenging. Consensus on the best surgical choice has not been demonstrated. In this study, we aim to report our experience in treating recurrent ureteral stricture and demonstrate whether robot-assisted procedure for redo ureteral surgery is as effective as open procedure while remaining less invasive. METHODS: We retrospectively assessed 41 patients (22 robot-assisted surgeries and 19 open surgeries) who underwent consecutive robot-assisted and open procedures for redo ureteral surgery from January 2014 to 2018 in our institution. Perioperative outcomes, including demographics, operative time, estimated blood loss, complications, pain scores, success rate and cost, were compared between two groups. RESULTS: There was no significant intergroup difference in terms of age, body mass index, gender composition and American Society of Anesthesiologists scores. A total of 31 patients underwent redo pyeloplasty and ten underwent redo uretero-ureterostomy. Compared with open group, robot-assisted group showed shorter operative time (124.55 min vs. 185.11 min, p < 0.0001), less estimated blood loss (100.00 mL vs. 182.60 mL, p = 0.008) and higher cost (61161.77¥ vs. 39470.79¥, p < 0.0001). Complication rate and pain scores were similar between two groups. Median follow-up periods were 30 and 48 months for robot-assisted and open group respectively. Success rate in the robot-assisted (85.71%) and the open group (82.35%) was not significantly different. CONCLUSIONS: Robot-assisted surgery for recurrent stricture after previous ureteral reconstruction is as effective as open procedure and is associated with shorter operative time and less estimated blood loss.

Rigid ureteroscopic lithotripsy versus percutaneous nephrolithotomy for large proximal ureteral stones: A meta-analysis.

OBJECT: To compare the safety and efficacy of rigid ureteroscopic lithotripsy (rigid URSL) and percutaneous nephrolithotomy (PCNL) in treating large proximal ureteral stones. METHODS: A systematic search of PubMed, EMBASE, Cochrane Library, and Web of Science databases was performed to find out relevant studies. After literature screening according to the predetermined inclusion and exclusion criteria, data of eligible studies was extracted and then a meta-analysis was conducted via RevMan 5.3 software. RESULTS: Five randomized controlled trials (RCTs), one prospective and four retrospective cohort studies involving 837 patients were included. Patients underwent rigid URSL were associated with shorter operation time (WMD, -23.66min; 95%CI, -45.00 to -2.32; p = 0.03), shorter hospital stay (WMD, -2.76d; 95%CI, -3.51 to -2.02; p< 0.00001), lower 3rd-day (RR, 0.73; 95%CI, 0.66 to 0.82; p < 0.00001) and 1st-month (RR, 0.82; 95%CI, 0.77 to 0.87; p < 0.00001) stone-free rate, higher risk of conversion to other surgical procedures (RR, 4.28; 95%CI, 1.93 to 9.46; p = 0.0003), higher incidence of migration (RR, 28.49; 95%CI, 9.12 to 89.00; p < 0.00001) and ureteral perforation (RR, 6.06; 95%CI, 1.80 to 20.44; p = 0.004), lower risk of fever (RR, 0.64; 95%CI, 0.42 to 0.97; p = 0.04), transfusion (RR, 0.19; 95%CI, 0.04 to 0.85; p = 0.03) and hematuria (RR, 0.38; 95%CI, 0.25 to 0.57; p < 0.0001). No significant difference was observed in terms of incidence of embolization, pain and ureterostenosis. When cohort studies or studies in which flexible ureteroscopy was used as an intraoperative auxiliary procedure were excluded, we both found that most of the results kept stable. CONCLUSIONS: Both PCNL and rigid URSL are safe for patients with large proximal ureteral stones while PCNL is more effective in stone clearance.

Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis.

Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31-16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07-18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, -1.04-2.80; p = 0.37 and WMD, -0.63 ng/mL; 95% CI, -2.72-1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15-18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, -0.20-5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99-9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14-7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, -5.00-18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, -3.55-5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.