Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5 +/- 10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7 +/- 12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions:68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC

Our study aimed to apply a proteomic approach to investigate the molecular mechanisms underlying the effects of oxalate on rat renal tubular epithelial cells. NRK-52E cells were treated with or without oxalate and subjected to quantitative proteomics to identify key proteins and key pathological changes under high oxalate stimulation. A total of 268 differentially expressed proteins (DEPs) between oxalate-treated and control groups were identified, with 132 up-regulated and 136 down-regulated proteins. Functional enrichment analysis revealed that DEPs are associated with oxidative stress, apoptosis, ferroptosis, pro-inflammatory cytokines, vitamin D, and biomineralization. SPP1, MFGE8, ANKS1A, and NAP1L1 were up-regulated in the oxalate-treated cells and the hyperoxaluric stone-forming rats, while SUB1, RNPS1, and DGLUCY were down-regulated in both cases. This altered proteomic landscape sheds light on the pathological processes involved in oxalate-induced renal damage and identifies potential biomarkers and therapeutic targets to mitigate the effects of hyperoxaluria and reduce the risk of CaOx stone formation.

Our study aimed to elucidate the mechanisms behind the interaction between calcium oxalate (CaOx) crystals and renal tubular epithelial cells through transcriptome sequencing analysis. HK-2 cells were stimulated with or without CaOx monohydrate crystals and subjected to RNA-seq to assess the effects of CaOx crystals on gene expression changes, key pathways, and molecular players during this interaction. A total of 629 differentially expressed genes (DEGs) were identified between the control group and experimental group, with 491 genes up-regulated and 138 down-regulated. Functional enrichment analysis indicated that the DEGs were significantly associated with endoplasmic reticulum stress (ERS) and unfolded protein response. To validate our findings, we compared our results with the public dataset GSE73680 and confirmed the increased expression of two ERS-related DEGs, CHAC1 and FGF21, in renal papillary tissues from patients with CaOx stones. Collectively, these findings suggest that ERS plays a crucial role in the crystal–cell interaction and highlight the potential for developing therapeutic strategies aimed at reducing CaOx stone formation by targeting ERS-related molecules and pathways.

This review discusses recent advances in robotic surgery for urologic tumors, focusing on three key areas: robotic systems, assistive technologies, and artificial intelligence. The Da Vinci SP system has enhanced the minimally invasive nature of robotic surgeries, while the Senhance system offers advantages such as tactile feedback and eye-tracking capabilities. Technologies like 3D reconstruction combined with augmented reality and fluorescence imaging aid surgeons in precisely identifying the anatomical relationships between tumors and surrounding structures, improving surgical efficiency and outcomes. Additionally, the development of artificial intelligence lays the groundwork for automated robotics. As these technologies continue to evolve, we are entering an era of minimally invasive, precise, and intelligent robotic surgery.

Calcium oxalate (CaOx) stones are the most prevalent type of kidney stones. CaOx crystals can stimulate reactive oxygen species (ROS) generation and induce renal oxidative stress to promote stone formation. Intracellular Ca2+ is an important signaling molecule, and an elevation of cytoplasmic Ca2+ levels could trigger oxidative stress. Our previous study has revealed that upregulation of Ang II/AT1R promoted renal oxidative stress during CaOx exposure. IP3/IP3R/Ca2+ signaling pathway activated via Ang II/AT1R is involved in several diseases, but its role in stone formation has not been reported. Herein, we focus on the role of AT1R/IP3/IP3R-mediated Ca2+ release in CaOx crystals-induced oxidative stress and explore whether inhibition of this pathway could alleviate renal oxidative stress. NRK-52E cells were exposed to CaOx crystals pretreated with AT1R inhibitor losartan or IP3R inhibitor 2-APB, and glyoxylic acid monohydrate-induced CaOx stone-forming rats were treated with losartan or 2-APB. The intracellular Ca2+ levels, ROS levels, oxidative stress indexes, and the gene expression of this pathway were detected. Our results showed that CaOx crystals activated AT1R to promote IP3/IP3R-mediated Ca2+ release, leading to increased cytoplasmic Ca2+ levels. The Ca2+ elevation was able to stimulate NOX2 and NOX4 to generate ROS, induce oxidative stress, and upregulate the expression of stone-related proteins. 2-APB and losartan reversed the referred effects, reduced CaOx crystals deposition and alleviated tissue injury in the rat kidneys. In summary, our results indicated that CaOx crystals promoted renal oxidative stress by activating the AT1R/IP3/IP3R/Ca2+ pathway. Inhibition of AT1R/IP3/IP3R-mediated Ca2+ release protected against CaOx crystals-induced renal oxidative stress. 2-APB and losartan might be promising preventive and therapeutic agents for the treatment of kidney stone disease.

Urolithiasis is a common urological disease with increasing prevalence and high recurrence rates around the world. Numerous studies have indicated reactive oxygen species (ROS) and oxidative stress (OS) were crucial pathogenic factors in stone formation. Dietary polyphenols are a large group of natural antioxidant compounds widely distributed in plant-based foods and beverages. Their diverse health benefits have attracted growing scientific attention in recent decades. Many literatures have reported the effectiveness of dietary polyphenols against stone formation. The antiurolithiatic mechanisms of polyphenols have been explained by their antioxidant potential to scavenge free radicals and ROS, modulate the expression and the activity of endogenous antioxidant and prooxidant enzymes, regulate signaling pathways associated with OS, and maintain cell morphology and function. In this review, we first describe OS and its pathogenic effects in urolithiasis and summarize the classification and sources of dietary polyphenols. Then, we focus on the current evidence defining their antioxidant potential against stone formation and put forward challenges and future perspectives of dietary polyphenols. To conclude, dietary polyphenols offer potential applications in the treatment and prevention of urolithiasis.

Androgen receptor (AR) signaling is essential in prostate cancer treatment. For many years, androgen deprivation therapy (ADT) has been primarily applied to manage advanced prostate cancer. However, most individuals with metastatic hormone-sensitive prostate cancer (mHSPC) administered ADT alone are at risk of developing metastatic castration-resistant prostate cancer (mCRPC) in less than two years. New approaches employing novel AR inhibitors (ARi) as intensified upfront systemic treatment in mHSPC have recently demonstrated substantial benefits in delaying disease progression and prolonging overall survival. Administration of novel ARi has become the new standard of care in mHSPC. The new landscape simultaneously makes treatment choice more challenging. This review provides comprehensive data on molecular structure, pharmaceutical properties, and efficacy and safety profiles reported by pivotal clinical trials. We also discuss future directions with ongoing Phase III trials of novel ARi in mHSPC. Considering these biological and clinical insights, this review aimed to provide a comprehensive understanding of differences in the development and applications of novel ARi for mHSPC, which may be helpful in designing strategies for first-line treatment choices.

Background The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall’s plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. Methods The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Results Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. Conclusion We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.

经皮肾造瘘术和经皮肾镜取石术(percutaneous nephrolithotripsy,PCNL)并发脾脏损伤是一项罕见但可能致命的并发症,国外报道 20 余例[1-3],国内仅2 例报道[4-5].华中科技大学同济医学院附属同济医院收治 2 例经皮肾手术并发脾脏损伤的患者,现报告如下.

Prostate cancer (PCa) is one of the malignant tumors of urinary system with a high morbidity. Enhancer RNA is a subclass of long non-coding RNA transcribed from active enhancer regions, which plays a critical role in gene transcriptional regulation. However, the role of enhancer RNA (eRNA) in PCa remains extremely mysterious. This study is aimed at exploring key prognostic eRNAs in PCa. First, we downloaded gene expression data and clinical data of 33 cancer types from UCSC Xena platform. Second, we selected reported putative eRNA-target pairs and performed the Kaplan–Meier survival and correlation analysis to determine the crucial eRNAs most related to biochemical recurrence (BCR)-free survival. Third, we explored the clinical characteristics with the key eRNA GAS1 adjacent regulatory RNA (GAS1RR) and performed a computational difference algorithm and the Cox regression analysis. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the underlying mechanisms. Finally, we used the pan-cancer data from The Cancer Genome Atlas (TCGA) and performed reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of 18 pairs of specimens to prove the results we acquired. Among all 2695 putative eRNAs, 6 pairs of eRNA-target genes were prominently related to BCR-free survival. Growth arrest-specific protein 1 ( GAS1) was a target gene of GAS1RR ( r = 0.86, P < 0.001). Patients with low GAS1RR expression were likely to have unfavorable clinical characteristics. The result of computational Cox regression analysis demonstrated that GAS1RR may predict the prognosis of PCa independently. RT-qPCR results illuminated that GAS1RR and GAS1 were both downregulated in PCa tissues, and they show a strong positive correlation. GO and KEGG analyses revealed biological processes that GAS1RR was mainly associated with. Immune infiltration analysis indicated that GAS1RR expression is correlated with the infiltration level of six kinds of immune cells. Our results suggest that GAS1RR may be clinically useful in the prediction of PCa prognosis. Moreover, it may also be a prognostic predictor and theoretic target with great promise in PCa.

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

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.

Idiopathic hypercalciuria is an important risk factor for the formation of calcium-containing kidney stones. Matrix metalloproteinase-9 (MMP-9) is closely related to cell and tissue remodeling and is involved in ectopic tissue calcification. However, little is known about its role in kidney stone formation. In this study, we found that the expression of MMP-9 and that of osteoblastic-related proteins was increased in normal rat kidney epithelial-like (NRK-52E) cells following treatment with a high concentration of calcium, while the knockout or overexpression of MMP-9 could, respectively, significantly inhibit or upregulate the expression of osteoblastic-related proteins and calcium crystal deposition. In addition, apoptosis and calcium crystal deposition were significantly reduced in Sprague–Dawley rats with 1,25(OH)2D3-induced hypercalciuria following MMP-9 inhibitor I treatment. Furthermore, inhibiting reactive oxygen species (ROS) production or the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway significantly reduced calcium-induced MMP-9 expression and calcium crystal deposition. In summary, our results suggested that a high calcium concentration promotes epithelial–osteoblastic transformation and calcium crystal deposition in renal tubule cells by regulating the ROS/NF-κB/MMP-9 axis and identified a novel role for MMP-9 in regulating calcium-induced calcium crystal deposition in renal tubules.

The oxidative injury of renal tubular epithelial cells caused by inflammation and oxidative stress induced by hyperoxaluria is an important factor in the kidney calcium oxalate (CaOx) stone formation. Resveratrol (RSV) has been reported to reduce oxidative injury to renal tubular epithelial cells, and autophagy is critical for the protective effect of resveratrol. However, the protective mechanism of RSV in oxalate-induced oxidative injury of renal tubular cells and the role of autophagy in this process are still unclear. In our study, glyoxylic acid monohydrate-induced rats were treated with or without resveratrol, and it was detected that the overexpression of oxidant species, CaOx crystal deposition, apoptosis level, inflammatory cytokines and osteoblastic-associated protein expression were reversed by resveratrol. Additionally, Resveratrol pretreatment significantly reversed oxalate -induced decline in cell viability, cell damage, oxidant species overexpression, and osteogenic transformation in normal rat kidney epithelial-like (NRK-52E) cells. Furthermore, we found that RSV pretreatment promoted intracellular LC3II upregulation, p62 downregulation, and autophagosome formation, whereas 3-methyladenine treatment reduced this effect. Moreover, RSV induced the expression of transcription factor EB (TFEB) in the nucleus of NRK-52E cells in a concentration-dependent manner. After transfection of NRK-52E cells with TFEB siRNA, we showed that the RSV-induced increase in TFEB expression and autophagosome formation were inhibited. Simultaneously, RSV-induced NRK-52E cells protection was partially reversed. These results suggested that RSV regulates oxalate-induced renal inflammation, oxidative injury, and CaOx crystal deposition in vitro and in vivo through the activation of a TFEB-induced autophagy.

目的:评估机器人辅助腹腔镜下前列腺癌根治术加扩大盆腔淋巴结清扫术治疗局部进展期前列腺癌的安全性及其疗效.方法:回顾性分析2015年12月-2019年12月我院收治的112例局部进展期前列腺癌患者的临床资料,放射性核素骨扫描排除骨转移后,行机器人辅助腹腔镜下前列腺癌根治术加扩大盆腔淋巴结清扫术,统计患者手术时间、术中出血量、清扫淋巴结个数、术后病理、住院时间等.结果:112例患者均顺利完成手术,平均手术时间(217.60±30.19)min,平均术中出血量(192.00±138.30) mL,常规术后2周拔除导尿管,平均术后住院时间(9.36±3.42)d.平均检出淋巴结(17.94±4.38)枚,淋巴结转移患者29例,检出阳性淋巴结共107枚,切缘阳性28例,术后淋巴漏21例,平均随访时间(34.69±11.25)个月.术后辅助内分泌治疗61例,放疗32例,出现生化复发44例.结论:局部进展期前列腺癌患者行机器人辅助腹腔镜下前列腺癌根治术加扩大盆腔淋巴结清扫术安全可行,临床疗效满意,并能清除潜在的转移淋巴结,提供精确的肿瘤病理分期,有望改善患者预后.

BACKGROUND:To introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19).METHODS:All emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study's COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods.RESULTS:The total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period.CONCLUSIONS:Urological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.

为了评价经尿道联合经阴道Smooth模式铒激光(Er∶YAG)照射治疗女性压力性尿失禁(SUI)的安全性和有效性,本研究选取了2018年10月—2019年9月期间于我院门诊就诊的21例患有轻中度SUI的已婚成年女性.所有患者均在局部麻醉下分3次接受经尿道联合经阴道Smooth模式铒激光照射治疗,每次治疗间隔4周并对治疗前、治疗后1个月和3个月的疗效以及相关不良事件分别进行统计和随访.疗效的统计随访采用国际尿控学会(ICS)标准化1 h尿垫试验(ICS-pad test)和国际尿失禁咨询委员会尿失禁问卷简表(ICIQ-SF),统计学分析采用配对样本t检验.结果显示,治疗后1个月和3个月随访的ICIQ-SF评分和1 h尿垫试验显著下降(P＜0.05),术后3个月有效率为81％,治疗后均未出现严重不良反应.提示经尿道联合经阴道Smooth模式铒激光照射治疗方式具有治疗时间短、治疗效果明显的优势,对治疗轻中度女性SUI是安全有效的.

Percutaneous nephrolithotomy (PCNL) has become a routine surgical procedure for treating patients with large kidney stones; the fundamental step in this process is the creation of the nephrostomy tract. In the present study, a meta-analysis was performed to compare the effectiveness and safety of different tract dilation techniques for PCNL. Databases were searched from inception to 1 April 2019 to identify relevant randomized controlled trials. The X-ray exposure time, hemoglobin decrease, stone-free rate, transfusion rate, hospital stay and the complication rate associated with the various techniques were analyzed. A total of 11 studies comprising 1,415 cases were enrolled in the meta-analysis. Significant differences in X-ray exposure time [weighted mean difference (WMD), 30.67; 95% confidence interval (CI), 20.08-41.26; P<0.001] and hemoglobin decrease (WMD, 0.19; 95%CI, 0.15-0.23; P<0.001) were identified between metal telescopic dilation (MTD) and one-shot dilation (OSD). A significantly lower hemoglobin decrease was observed in the balloon dilation (BD) vs. fascial Amplatz dilation (AD) group [WMD, -0.65; 95%CI, -(0.77-0.52); P<0.001]. The transfusion rate was similar between these techniques. The MTD had an obviously higher successful dilation rate compared with that of the OSD, but no significant differences in stone-free rate and transfusion rate were obtained. The present study determined that, compared with other methods, OSD was safer in almost every adult patient, including those that had previously undergone renal surgery; though it is recommended that this should be performed by experienced surgeons. BD was reported to be effective and safer in patients without a history of renal surgery compared to other methods. The present study proposed AD and MTD as safer methods of dilation for patients who have previously undergone kidney surgery.

目的:Randall钙斑是位于肾乳头间质的异位钙化,被认为是草酸钙结石的起始病变.这些钙盐沉积可能源于异位钙化相关基因表达失调,并在宏观上导致肾乳头密度增加.本研究拟探究肾结石患者和非结石对照者肾乳头CT值和钙化抑制相关基因表达的差异.方法:纳入60例具有腹部CT平扫影像的肾结石患者作为结石组.选取60例具有腹部CT影像,且与结石患者年龄性别相匹配非结石患者作为对照组.每组均各纳入男40例,女20例.两组平均年龄分别为(48.67±11.14)岁和(48.40±10.73)岁.在平扫CT上测量其肾脏上盏、中盏和下盏肾乳头密度并比较.检索和下载Gene Expression Omnibus数据库Randall钙斑芯片GSE73680数据文件.分析比较5种钙化抑制相关基因包括基质Gla蛋白(MGP)、骨桥蛋白(OPN)、骨钙素(OCN)、骨保护素(OPG)和富Gla蛋白(GRP)在结石组和对照组患者肾乳头组织的表达情况.结果:结石组患者肾乳头密度均值显著高于对照组[(49.19±7.26) HU vs.(41.11±5.55) HU].与对照组相比,结石组肾乳头OPN、OPG、OCN和GRP表达分别是对照组1.93倍、1.16倍、1.57倍和2.04倍,P值分别为0.52、0.58、0.06和0.08.MGP在结石患者肾乳头表达下调3.15倍(P=0.05).结论:结石患者肾乳头密度显著增高,抑制钙化相关基因MGP表达降低.

Objective To observe the effect of dimethyl fumarate (DMF) on the renal calcium oxalate crystals formation in SD rats induced by glyoxylic acid monohydrate,and explore the possible mechanism.Methods Thirty male Sprague-Dawley rats were randomly divided into 3 groups:control group,model group and DMF group (n =10 each).The control group was free to drink purified water.Model group was induced by intraperitoneal injection of glyoxylic acid monohydrate to establish a kidney calcium oxalate stone model,and DMF group was treat with DMF by gastric administration on the basis of modeling.After 10 days of continuous treatment,the 24 h urine,serum and kidney of rats in each group were collected.Serum creatinine (SCr) value,calcium and oxalate (Ox) contents in urine were measured.Von Kossa staining method was used to detect the deposition of calcium oxalate crystals in kidney tissue.Western blotting was used to detect the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 protein in renal tissue.The frozen section DHE staining was used to detect the ROS level in the kidney,thiobarbituric acid method was used to test malondialdehyde (MDA) content,and the xanthine ox idase method was used to detect superoxide dismutase (SOD) activity.Results There was no visible calcium crystal in the kidney of the control group.Compared to the model group,the amounts of renal calcium crystal were significantly reduced in the DMF group (76.07 ±4.87) /HP vs.(37.94 ±4.63) /HP (t =17.940,P ＜ 0.01);For control group,model group,and DMF group,the SCr concentrations were (29.77 ±2.42),(74.77 ±9.64),(42.64 ± 14.35) μmol/L,respectively;24-hour urinary Ox con tents were (3.28 ± 1.03),(13.56 ± 3.26),(13.74 ± 3.18) mg,respectively;calcium ion contents were (0.96 ± 0.20),(0.79 ± 0.22),(0.84 ± 0.22) mg,respectively;kidney MDA concentrations were (3.84 ± 0.42),(8.22 ± 0.63),(4.79 ± 0.47) nmo]/mg,respectively;the expressions of kidney SOD were (635.83 ± 121.45),(363.33 ± 115.02),(528.83 ± 107.48) U/mg,respectively.Compared to the control group,the SCr (t =14.320,P ＜0.01) and MDA (t =18.290,P ＜0.01) concentration were significantly elevated in model group,but the expressions of SOD reduced significantly (t =5.150,P ＜ 0.01).Compared to the model group,the SCr (t =5.880,P ＜ 0.01) and tissue MDA concentration (t =13.800,P ＜0.01) were significantly reduced in the DMF group,but the expressions of SOD increased significantly (t =3.330,P ＜ 0.01);Compared with the control group,the 24-hour urinary oxalate content in the model group (t =9.510,P ＜ 0.01) and the DMF group (t =9.900,P ＜ 0.01) were significantly elevated.There was no significant difference in urinary oxalate content between the model group and the DMF group (t =0.130,P ＞0.05).There was no significant difference in 24-hour urinary calcium ion content between the three groups (F =1.670,P ＞ 0.05).Compared with the control group,renal ROS levels (t=20.920,P＜0.01),Nrf2 (t=17.290,P＜0.01) and HO-1 protein (t=38.030,P＜ 0.01) expression levels were significantly increased in the model group.Compared with the model group,renal ROS levels were significantly reduced in the DMF group (t =16.000,P ＜ 0.01),while the expres sion levels of Nrf2 (t =25.580,P ＜ 0.01) and HO-1 protein (t =79.290,P ＜ 0.01) were significantly increased.Conclusion The formation of calcium oxalate kidney stones is related to oxalate-mediated ox idative stress.DMF may interfere with the pathogenesis of calcium oxalate kidney stones by activating Nrf2 to induce HO-1 to inhibit oxidative stress.