Increased urinary angiotensinogen precedes the onset of albuminuria in normotensive type 2 diabetic patients

It was previously reported that intrarenal renin angiotensin system (RAS) plays a pivotal role in the onset and progression of diabetic nephropathy (DN). Urinary angiotensinogen (UAGT) was employed as a special index of the intrarenal RAS status and enhanced significantly at a very early stage of chronic kidney disease and type 1 diabetes. On the basis of these findings, the present study was performed to test the hypothesis that UAGT levels are increase even before the development of DN in type 2 diabetic patients without hypertension. 102 patients with type 2 diabetes mellitus (T2DM) and 18 healthy volunteers were studied cross-sectionally. Clinical data were collected and morning spot urine samples were obtained from all participants. UAGT levels were detected by an enzyme-linked immunosorbent assay (ELISA). As a result, UAGT to creatinine ratio (UAGT/Cr) was significantly enhanced in T2DM patients before the appearance of urinary albumin (UALB) and further increased to a greater degree in albuminuric patients. UAGT/Cr levels were positively correlated with Log (UALB to creatinine ratio) and diastolic blood pressure, but negatively correlated with estimated glomerular filtration rate. These data indicate that elevated UAGT levels precede the onset of albuminuria in normotensive T2DM patients. UAGT might potentially serve as an early marker to determine intrarenal RAS activity and predict progressive kidney disease in T2DM patients without hypertension.     

ShRNA-mediated silencing of the ubiquitin-specific protease 22 gene restrained cell progression and affected the Akt pathway in nasopharyngeal carcinoma

Ubiquitin-specific protease 22 (USP22) is closely related with poor prognosis of cancer patients. However, the role of USP22 expression in nasopharyngeal carcinoma (NPC) has not been determined. The main aim of this study was to determine the role of USP22 in the pathologic processes of NPC. Immunohistochemistry (IHC), western blot (WB), and real-time polymerase chain reaction (RT-PCR) were used to measure the expression of USP22 in cell lines and tissues of NPC in comparison with expression in non-cancerous cells and tissues. USP22-specific short hairpin RNA (shRNA) was used to knock down USP22 expression in the NPC cell line CNE-1 and CNE-2. Furthermore, the impact of USP22 in cellular proliferation, growth, and cell cycle were detected respectively. WB was used to determine the role of USP22 in the AKT/GSK-3/Cyclin signaling pathway. The expression levels of USP22 were remarkably higher in NPC cell lines and tissues. With cell counting and the MTS assay, cellular growth and proliferation progression of USP22 knockdown cell line was shown to be effectively restrained. The USP22 silencing both in CNE-1 and CNE-2 cells caused them to accumulate in the G0/G1 phase of the cell cycle. USP22 knockdown was also found to modulate the AKT/GSK-3/Cyclin pathway, resulting in downregulation of p-AKT, p-GSK-3β, and cyclinD1. This study suggests that USP22 plays a critical regulatory role in the pathologic processes of NPC, and that it may be a potential biological treatment target in the future.     

Poly(ADP-ribose) glycohydrolase silencing down-regulates TCTP and Cofilin-1 associated with metastasis in benzo(a)pyrene carcinogenesis

Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant. BaP is a known carcinogen and can induce malignant transformation of rodent and human cells. Many evidences suggest that inhibitor of poly(ADP-ribose) glycohydrolase (PARG) is potent anticancer drug candidate. However, the effect of PARG on BaP carcinogenesis remains unclear. We explored this question in a PARG-deficient human bronchial epithelial cell line (shPARG cells) treated with various concentration of BaP for 15 weeks. Soft agar assay was used to examine BaP-induced cell malignancy of human bronchial epithelial cells and shPARG cells. Mechanistic investigations were used by 2D-DIGE and mass spectrometry. Western blot analysis and Double immunofluorescence detection were used to confirm some of the results obtained from DIGE experiments. We found that PARG silencing could dramatically inhibit BaP-induced cell malignancy of human bronchial epithelial cells in soft agar assay. Altered levels of expression induced by BaP were observed within shPARG cells for numerous proteins, including proteins required for cell mobility, stress response, DNA repair and cell proliferation pathways. Among these proteins, TCTP and Cofilin-1 involved in malignancy, were validated by western blot analysis and immunofluorescence assay. PARG inhibition contributed to down-regulation of TCTP and Cofilin-1. This is the first experimental demonstration of a link between PARG silencing and reduced cell migration after BaP exposure. We propose that PARG silencing might down-regulate TCTP and Cofilin-1 associated with metastasis in BaP carcinogenesis.     

肝癌合并门静脉高压术中脾动脉结扎的临床疗效观察

目的探讨肝癌切除术中行脾动脉结扎治疗肝癌合并门静脉高压的临床疗效。方法回顾性分析2008年1月至2013年1月收治的肝癌合并门静脉高压患者临床资料和手术疗效,对照组患者共33例仅进行肝癌切除术,试验组患者共38例于肝癌切除术中行脾脏动脉结扎。采用SPSS16.0统计软件,对两组患者术前术后1~3个月门静脉压力、血常规检测、脾静脉血流流量等上述指标以x珋±s表示,采用t检验,P<0.05表示差异有统计学意义。结果术后1、2、3个月血象(血细胞三系)和脾静脉血流数值:试验组患者红细胞数、白细胞数、血小板数显著高于对照组(t值分别为:3.457、2.876、2.987;2.975、3.112、2.986;2.964、3.587、3.457。P<0.05),试验组患者脾静脉血流显著低于对照组(t值分别为:2.991、2.989、2.891,P<0.05),两组差异有统计学意义,结果提示脾动脉结扎在短期(4个月)内可明显改善肝硬化所致门静脉高压-脾功能亢进状况。术后4个月,两组患者红细胞数、白细胞数、血小板数及脾静脉血流量比较无明显差异P>0.05。结论肝癌切除术中行脾动脉结扎治疗肝癌合并门静脉高压短期内可有效缓解肝硬化所致门静脉高压-脾功能亢进状况。     

Varicocele anatomy during subinguinal microsurgical varicocelectomy in Chinese men

Knowledge of subinguinal microsurgical varicocelectomy is of fundamental importance to ensure that varicocele is resolved and testicular function is preserved. Our study aimed to describe the number of veins, arteries and lymphatics in the subinguinal spermatic cord and to clarify their differences between two sides, between patients with different complaints and between varicoceles with different clinical grades. A total of 102 consecutive patients underwent 162 primary subinguinal microsurgical varicocelectomies, during which the number of vessels with different diameters was recorded. A mean number of 12.9 internal spermatic veins, 0.9 external spermatic veins, 1.8 internal spermatic arteries and 2.9 lymphatics were identified per cord. 88.2% of the internal spermatic arteries were surrounded by a dense complex of adherent veins. The external spermatic vein or veins were found in 49.4% of the cases. The mean number of medium (1–3 mm in diameter) internal spermatic veins on the left was larger than that on the right (P < 0.001). The mean number of medium internal spermatic veins in grade III varicocele was larger than that in grade I or grade II (P < 0.015). There was no significant anatomical difference between the men presenting for infertility, chronic testicular pain and both the two complaints.