草酸钙肾结石是肾结石的主要类型,是草酸积存过多所致,具有质硬、不规则、不易碎、粗糙等特点,易损伤组织.微创外科手术的发展能够有效提升肾结石治疗有效率,但无法作用于病因,术后复发率未得到有效解决.中医药治疗肾结石具有多年历史,尤其是利水渗湿中药在草酸钙结石防治中具有独特优势.本文就利水渗湿中药在防治草酸钙肾结石中的应用效果进行综述,旨在为临床提供参考.

Objective:To explore the correlation between single nucleotide polymorphism (SNP) of Keap1 gene and clear cell renal cell carcinoma (ccRCC),and to provide an effective molecular target for the clinical diagnosis and treatment of the ccRCC.Methods:One hundred and eight carcinoma tissues from the patients with ccRCC (tumor group) and 86 normal renal tissues from the tumor-free individuals (control group) were collected.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and gene sequencing assays were used to detect NSP of the Keap1 gene and genotype of the samples of the both groups.Expression status of the Keap1 gene in the both groups were examined by real-time fluorescence quantitative PCR.Results:Distribution frequencies of the Keap1 gene rs1048289 in different genotypes and alleles were statistically different between the tumor group and the control group (P ＜ 0.05).Risk of ccRCC in the patients carraying AA genotype and A allele obviously increased,and AA genotype (OR =2.292,95％ CI:1.159-4.533,P ＜ 0.05) and A allele (OR =2.067,95％ CI:1.280-3.342,P ＜ 0.01) were risk factors of ccRCC.Expression of the Keap1 gene in the patients of the tumor group was significantly lower than that in the patients of the control group (P ＜ 0.05).But there was no obvious difference in expression of the Keap1 gene among samples with different genotypes (P ＜ 0.05).Conclusion:The Keap1 gene rs1048289 could be significantly correlated with ccRCC,and could hopefullv become an effective molecular target for early diagnosis and gene therapy of the patients with ccRCC.

Objective To observe the mechanism of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome to the formation of calcium oxalate stone after exposure to high concentrate of oxalate.Methods The human kidney proximal tubular epithelial HK-2 cells were cultured and stimulated with different concentrations of soluble oxalate cells.Lactate dehydrogenase (LDH) released assays from cell culture medium and 4',6-dianidino-2-phenylindole (DAPI) staining were used to determine the effect of cellular toxicity and injury after exposure to oxalate.All the cells of oxalate group and control group were incubated with calcium oxalate monohydrate (COM) crystals for 24 h,and cell surface adhesion of crystals were observed using an inverted phase-contrast microscope.Western blotting and real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) were applied to detect protein level and mRNA quantity of NLRP3,cysteinyl aspartate-specific protease-1 (Caspase-1),and interleukin-1β (IL-1 β) from HK-2 cell lysates after exposure to oxalate.FQ-PCR was applied to analyse mRNA quantity of hyaluronan synthase 1 (HAS1),hyaluronan synthase 2 (HAS2),hyaluronan synthase 3 (HAS3),osteopontin (OPN) and CD44 from HK-2 cell after exposure to oxalate.Intracellular reactive oxygen species (ROS) generation was estimated by the method of using 2',7'-dichlorofluorescein diacetate (DCFH-DA) as per constructor's protocol after exposure to oxalate.Thereafter,N-acetylcysteine (NAC),a scavenger of ROS was pre-treated with HK-2 cells for 2 h,and Western blotting and FQ-PCR were applied to detect protein level and mRNA quantity of NLRP3 gene.HK-2 cells were transfected by NLRP3-small interfering RNA (siRNA).After oxalate stimulation,an inverted phase-contrast microscope was used to detect the number of the binding COM crystals on the surface of the cells,and the levers of HAS1,HAS2,HAS3,OPN and CD44 mRNA through FQ-PCR.Results Exposure of HK-2 cells to different concentrations of oxalate for 24 h,it observed that exposure to the oxalate concentrations (0.8 mmol/L) led to significantly higher in LDH release than the oxalate concentrations (0.6 mmol/L) [(528.37 ±25.65) vs.(300.55 ± 17.18) mmol/L,P =0.001],and the DAPI staining showed different cell number:55.67 ±3.30,52.33 ±6.13,52.33 ±2.05,58.00 ±9.09,50.00 ± 1.63,47.33 ± 2.05,33.67 ± 3.30,20.33 ± 2.05,and the result showed that exposure to the oxalate concentrations (1.0 mmol/L) led to a meaningful reduction in the number of cells compared with the oxalate concentrations (0.8 mmol/L) (33.67 ±4.04 vs.47.33 ±2.52,P =0.008).Using an inverted phase-contrast microscope observed that a significantly greater number of the binding COM crystals on the surface of the high-oxalate-exposed cells as compared to the controls [(7.34 ± 0.82) ％ vs.(5.29 ± 0.73) ％,P =0.001].Exposure of HK-2 cells to high concentration oxalate for 24 h significantly increased the expression of protein (1.82 ±0.04 vs.1.00 ±0.02,P =0.000;1.62 ±0.23 vs.1.00 ±0.06,P =0.021;1.37 ±0.16 vs.1.00 ±0.18,P =0.029) and mRNA levels (1.15 ±0.26 vs.0.81 ±0.11,P =0.011;2.16±0.29 vs.1.04 ±0.14,P=0.009;1.80 ±0.02 vs.1.00±0.15,P=0.002)of NLRP3,Caspase-1,IL-1β when compared with the control,and the mRNA level (1.35 ±0.25 vs.0.81 ± 0.11,P=0.049;2.46±0.29 vs.0.84±0.14,P=0.002;0.90±0.02 vs.0.60±0.15,P=0.039;1.68 ± 0.27 vs.1.00 ± 0.22,P =0.049;2.03 ± 0.47 vs.1.00 ± 0.15,P =0.040) of HAS1,HAS2,HAS3,OPN and CD44 significantly up-regulated compared with the control.Exposure to high concentration of oxalate for 24 hours,the intracellular ROS levels of HK-2 were meaningfully increased (736.67 ± 80.21 vs.208.67 ± 35.73) by the method of using DCFH-DA (P =0.001).Cells were pre-incubated with a ROS scavenger (NAC) for 2 h,followed by treatment with oxalate.According to the western blotting analysis of HK-2 cell lysates,the blockade of ROS by NAC resulted in decreased the protein levels (1.53 ±0.31 vs.4.50 ±0.40)of NLRP3 gene in HK-2 cells (P =0.001),and that in the control and the NAC group were 0.90 ±0.10 and 1.00 ±0.26 respectively (P =0.288).The silencing of the NLRP3 gene obviously reduced the number of calcium oxalate crystals adhesion to cells [(1.87 ± 0.21) ％ vs.(3.57±0.12)％,P=0.003],and the mRNA levels (1.06 ±0.07 vs.2.44 ±0.47,P=0.015;0.87±0.07vs.1.48±0.22,P=0.021;1.24±0.16 vs.1.72±0.10,P=0.026;1.03±0.15 vs.1.45 ±0.09,P=0.026;0.63±0.07 vs.1.31±0.12,P=0.002) of HAS1,HAS2,HAS3,OPNand CD44 mRNA were also descended.Conclusion Activation of the NLRP3 inflammasome induces by the generation of ROS in the formation of calcium oxalate kidney stone;The NLRP3 inflammasome activation engages by changing the renal tubular epithelial adhesion of crystal and involved in the formation of the stone.

目的:探讨尿路上皮癌伴鳞状分化对初次经尿道膀胱肿瘤电切术(TURBT)术后pT1期患者预后的影响.方法:回顾性分析初次经TURBT手术、术后病理诊断为T1期的531例膀胱尿路上皮癌患者的临床病理资料.根据患者的术后病理诊断将患者分为2组:A组为尿路上皮癌(单纯型)441例,B组为尿路上皮癌伴鳞状分化90例,应用SPSS 20.0统计软件,运用Kaplan-Meier法分析两种临床病理特点对无复发生存期(RFS)和无进展生存期(PFS)的影响,并用Log-rank检验比较生存曲线;运用COX回归模型单因素和多因素分析膀胱尿路上皮癌伴鳞状分化与初次TURBT术后pT1期患者预后之间的关系,评估影响其RFS和PFS的因素.结果:A组单纯尿路上皮癌441例(83.05％),B组尿路上皮癌伴鳞状分化90例(16.95％).B组与A组比较更易具有高级别肿瘤(P＜0.001),同时B组较A组有较高的复发率(P=0.018)、较短的无复发生存期(P＜0.001)以及较高的进展率(P=0.001)、较短的无进展生存期(P＜0.001).B组与A组比较,年龄(P=0.185)、性别(P=0.135)、吸烟(P=0.728)、肿瘤大小(P=0.436)、肿瘤数目(P=0.112)和膀胱灌注(P=0.054)等差异均无统计学意义.COX多因素生存分析显示:吸烟(HR 1.34,95％ CI 1.00-1.79,P=0.048)、鳞状分化的伴发情况(HR 1.43,95％ CI 1.02-2.00,P=0.040)以及病理分级(HR 1.51,95％CI1.13-2.01,P=0.005)等因素显著增加TURBT术后pT1期患者的复发风险;同时,吸烟(HR 1.80,95％ CI 1.17-2.76,P=0.008)、鳞状分化的伴发情况(HR 2.07,95％ CI 1.32-3.24,P=0.001)以及病理分级(HR 1.90,95％ CI 1.24-2.92,P=0.003)等因素显著增加TURBT术后pT1期患者的进展风险.结论:尿路上皮癌伴鳞状分化是TURBT术后pT1期患者的预后独立影响因素,复发率及进展率较高,需密切随访.

Objective To explore the expression level and significance of the nod-like receptor protein 3 (NLRP3) inflammasome in renal tissue with calcium oxalate stone.Methods 20 kidney specimens were collected as the experimental group from patients with calcium oxalate stone who underwent nephrectomy because of stones in our hospital between January 2008 and December 2014;another 20 renal specimens were get as the control group from patients with renal carcinoma,the renal tissues were obtained 2cm far from the tumor and proved as normal tissue.Immunohistochemical detection was carried out to analyze the expression level of NLRP3,Caspase-1,and IL-1β in the 40 renal samples.Animal experiment:fourteen male SD rats were randomly divided into calcium oxalate stone group and control group.For calcium oxalate stone group we established an ethylene glycol method induced hyperoxaluric rat model featured by crystalline material within tubule lumens;for control group normal feeding was performed.After 6 weeks,all rats were sacrificed,and the kidneys were harvested for further experiments.HE staining and Pizzolato staining were used to detect calcium oxalate crystals within tubule lumens.Western boltting and RT-PCR was applied to detect protein level and mRNA quantity of NLRP3,Caspase-1,and IL-1β from tissue lysates in rat model.Results In renal tissue samples obtained from patients with calcium oxalate stone disease,we demonstrated that the expression level of NLRP3,Caspase-1,and IL-1β were above to the normal renal tissue samples.We established a hyperoxaluric rat model character with crystalline material within tubule lumens examined by renal histology with HE staining and Pizzolato staining.And we detected that the protein and mRNA levels of NLRP3,Caspase-1 and IL-1β were remarkably increased in the lysates from the hyperoxaluric rat model (P ＜ 0.05).Conclusions The NLRP3 inflammasome has overexpression in the renal tissue of patients with calcium oxalate stone as well as in the renal tissue of hyperoxaluric rat,and it provides a new thought to reveal the formation of calcium oxalate stone.

目的：分析前列腺恶性间叶性软骨肉瘤的诊疗特点。方法回顾性分析1例前列腺恶性间叶性软骨肉瘤患者的临床资料，并结合文献分析其临床表现、影像学检查、病理特点、治疗及预后。结果患者男，59岁。因尿频、进行性排尿困难于外院诊断为前列腺增生，行经尿道前列腺电切术治疗，术后病理示前列腺恶性间叶性肿瘤。B超检查示膀胱内中等回声团块，未见明显移动，前列腺显示不清，右侧盆腔内可见囊性混合型结构。全身骨扫描检查未见明确骨转移征象。前列腺MRI检查示盆腔内近盆底区可见多发结节状、团块状软组织信号影，较大者位于膀胱右侧。患者于全麻下行根治性膀胱切除术＋盆腔淋巴结清扫术＋双侧输尿管皮肤造口术，术后病理检查可见片状未分化的原始间叶细胞，其间散在小岛状高分化的软骨细胞，软骨细胞有轻度异型性。免疫组化：波形蛋白和软骨区域胞核S-100均阳性，未分化细胞区域S-100、平滑肌肌动蛋白、CD34、细胞角蛋白CK7、CK8均为阴性。病理诊断为前列腺恶性间叶性软骨肉瘤。患者术后拒绝接受化疗和其他进一步治疗，于术后3个月死亡。结论前列腺恶性间叶性软骨肉瘤患者临床表现以尿频、进行性排尿困难为主，需根据患者的临床表现、影像学检查、组织病理学与免疫组化等综合诊断，治疗首选手术根治切除，术后应针对性给予放疗或化疗。