The ubiquitin-specific protease ( USP) inhibitors influence many crucial cellular activities and some immune processes, such as anti-inflammatory, anti-infection and anti-tumor by silencing the functions of USP.The main USP inhibitors, which potency and specificity are underlined and current methods for detecting and identifying USP inhibitors are discussed of in this review.

Objective To explore whether the glomerular podocytes can be damaged by aristolochic acid. Methods Thirty-two male SD rats were equally divided into the following 2 groups:model group in which the rats received the extract of Aristolochia manshuriensis Kom (AmK) by gavage; control group only received tap water by gavage.24 h urinary protein excretion was measured at the end of the 1st and 4th week,and SDS-PAGE gel electrophoresis was performed to detect the protein in urine.At the end of the 4th week,all the rats were sacrificed and the glomeruli were isolated by laser capture microdissection technique.The mRNA expression of nephrin,podocin,CDA2P,podocalyxin and podoplanin in isolated glomeruli was determined by RT-PCR,and the average width of glomerular foot process was measured by electron microscopy and image analysis. Results At the end of the 4th week,24 h urinary protein excretion in the model group was significantly higher than that in the control group (P＜0.01) and the urinary albumin content in model group was also obviously increased.The average width of glomerular foot process in the model group was significantly larger than that in control group (P＜0.01).The mRNA expressions of nephrin,podocin,CDA2P,podocalyxin and podoplanin in glomeruli were significantly down-regulated in the model group compared with the control group,which decreased by 34％,62％,56％,50％(P＜0.01) and 27％ (P＜0.05),respectively. Conclusions Aristolochic acid can damage the glomerular podocytes,resulting in the down-regulation of nephrin,podocin,CD2AP,podoplanin and podocalyxin mRNA expression, the segmental widening of foot process, and increased urinary protein excretion.

Objective To study the pathogenesis of anemia in chronic aristolochic acid nephmpathy(CAAN) rats. Methods The hemoglobin(Hb)values of sixty-two male SD rats were assayed to determine its normal range.Among them,24 rats with normal Hb value were randomly divided into 2 groups:model group (MG)in which rats received the extract of Aristololochia manshuriensis Kom (AmK) by gavage,and control group (CG) received tap water only by gavage.Body weisht(BW),Hb,24 h urinary protein excretion(UP)and creatinine clearance (Ccr)of 6 rats in each group were measured before administration and at the end of the 8th week, respeetively.then these rats were sacrificed.The relative area of renal interstitial fibrosis was measured by microscopy.The mRNA expression of erythropoietin (EPO)in kidney tissue Was determined by real-time RT-PCR;protein expression of type I collagen(Coll),aminopeptidase P (APP),hypoxia indHeible factor let and 2α(HIF-1α and HIF-2α)in kidney tissue Was examined by immunohistochemistry staining. Results Hb values of normal rats presented normal distribution. The normal Hb was (155.9±16.5) g/L. Rat anemia was diagnosed when Hb was below 123.6 g/L. There was no difference in all the examination results between CG and MG before administration (P>0.05). Compared with CG, the Hb and Cer in MG were significantly decreased [(121.66±15.68) g/L vs (169.00±12.89) g/L, (0.63±0.13) ml/min vs (1.27±0.18) ml/min, P< 0.01], and the UP in MG was significantly increased at the end of the 8th week [(27.04±9.40) mg/d vs (6.11±0.84) mg/d, P<0.01]; the relative areas of fibrosis and Col l in renal interstitium of MG were significantly enlarged [(12.89±2.33)% vs (0.55±0.10)%, (13.92±2.92)% vs (1.32±0.84)%, P<0.01]; the protein expression of APP and the mRNA expression of EPO in the kidney tissue of MG were significantly down-regulated [(0.55±0.23)% vs (3.77±1.06)%, 0.005±0.001 vs 0.032±0.013, P<0.01]; the protein expression of HIF-lα and HIF-2α in the kidney tissue of MG was significantly up-regulated (2.55±0.16 vs 1.12±0.46, 2.33±0.33 vs 1.15±0.27, P<0.01), at the end of the 8th week. Conclusions The pathogenesis of anemia in CAAN may be due to the decreased production of EPO caused by the destruction of peritubular capillary. The compensatory up-regulation of HIF-lα and HIF-2α expression can not prevent the anemia development.

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.

Objective To investigate the impact of metabolic syndrome(MS)on clinicopathology of IgA nephropathy(IgAN). Methods A total of 118 IgAN patients complicated with MS were enrolled in the study as IgAN-MS group. Then 118 IgAN patients of same age arrange without MS were randomly selected as IgAN-non-MS group.A comparative analysis of clinical and pathological data between these two groups was performed. Results The urine protein, serum creatinine, body mass index, mean arterial pressure, serum triglyceride, fasting blood glucose and serum uric acid in IgAN-MS group were all significantly higher than those in IgAN-non-MS group(P<0.05 or P<0.01). The serum HDL-C level in IgAN-MS group was significantly lower than that in IgAN-non-MS group(P<0.01). The percentages of patient with hypertension, abnormal glucose metabolism or abnormal lipid metabolism in IgAN-MS group were also significantly higher than those in IgAN-non-MS group(P <0.01). The glomerular and tubulointerstitial pathological changes in IgAN-MS group were significantly more severe than those in IgAN-non-MS group(P<0.01). There were significantly positive correlations between MS and urinary protein quantity, serum creatinine level, and glomerular damage index or tubulointerstitial damage index(P<0.01)by Spearman rank correlation analysis. Conclusion MS may be an important risk factor of IgAN progression.

Objective To investigate the level and influencing factors of oral health-related quality of life in patients with chronic periodontal disease. Methods 280 patients with chronic periodontal disease were investigated, using Pearson, Spearman correlation and multivariate linear regression to identify influencing factors of oral health-related quality of life. Results The oral health impact profile was in the middle level with a total score of 16.93±7.37. The influencing factors were self-efficacy for self-care, dental fear and entering into supportive periodontal therapy, which contributed 24.0% of the variance. Conclusions The oral health-related quality of life in patients with chronic periodontal disease is in low level. In order to improve the oral health-related quality of life in patients with chronic periodontal disease, health care providers should strengthen patients′ self-efficacy and reduce the patients′dental fear.

Objective To explore the potential relationship between tryplase-positive mast cells (MCs) infiltration and renal interstitial fibrosis in acute interstitial nephritis (AIN) and chronic interstitial nephritis (CIN). Methods Renal biopsy specimens from patients with AIN (n=11) and CIN (n=16) were studied and 11 patients in minimal change diseases (MM)were as controls. Histochemistry and immunohistochemistry staining assay were applied to delect the expression of tryptase, proteinase-activated receptor-2 (PAR-2), TGF-?1 and collagen type I (Col I )in the renal tissues. Immunofluo-rescence double-staining assay was used to assess the relationship among MCs, PAR-2-positive cells, and TGF-?1-positive cells in the renal interstitium respectively. Results MCs in AIN and CIN were significantly increased compared with those in controls and were mainly scattered in the fibrotic areas of renal interstitium. The relative immunostaining areas for PAR-2, TGF-?1 in the renal tubular epithelial cells (RTECs) and Col I were significantly larger in AIN and CIN than those in controls respectively (P

Objective To explore the potential relationship between the mast cells (MCs) in renal interstitium and the renal interstitial fibrosis in lupus nephritis (LN). Methods Renal biopsy specimens from patients with types Ⅲ,Ⅳand Vof LN (n=10, respectively), and with minimal change diseases (n=11,as control) were evaluated. Immunohistochemistry staining and immunofluorescence double-staining were used to detect the amount of MCs, the expression of proteinase-activated receptor-2 (PAR-2), transforming growth factor-?1 (TGF-?1) and collagen type I (Col I ) in the renal tissues. Results The amount of MCs in renal interstitium, the positive areas of PAR-2 and TGF-?1 in the renal tubular epithelial cells (RTECs), the amount of PAR-2-positive cells and TGF-?1-positive cells in renal interstitium, and the positive areas of Col I in the renal inter stitium were all higher in three LN groups compared with those in control. Furthermore, among the three LN groups, the above-mentioned parameters were the highest in type Ⅳ and second in type Ⅲ.There were significant positive correlations between the amount of MCs in renal interstitium and the positive areas of PAR-2, TGF-?1 in RTECs as well as the positive areas of Col I in renal interstitium (r=0.513, 0.508, 0.611, respectively, P

Objective To establish a model of chronic aristolochic acid nephropathy (CAAN) in rats and to investigate the pathogenesis of its renal interstitial fibrosis.Methods Male Sprague-Dawley rats were randomly divided into two groups. One group received extract of Aristolochia manshuriensis Kom by gavage intermittently as model group. Another group received only tap water by gavage as controls. Six rats in each group were sacrificed at the end of 4th, 8th and 12th week respectively and the kidneys of each rat were separately harvested. The mRNA and protein expression of type I collagen (Col I ), transforming growth factor-?1 (TGF-?1), connective tissue growth factor (CTGF), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) was detected by real-time quantitative RT-PCR and immunohistochemical staining respectively. Results The mRNA expression of Col I, TGF-?1, CTGF, PAI-1 and TIMP-1 in kidney tissue of the rats in model group was significantly upregulated compared to that in controls at the end of 4th week (9.31-, 5.16-, 1.79-, 8.66- and 2.54-fold, respectively) (P

ObjectiveTo investigate the clinical characteristics,diagnosis,treatment and prognosis of limited stage primary esophageal small cell carcinoma (PESC).MethodsClinical data was retrospectively analyzed for 42 patients with pathologically confirmed PESCs who underwent transthoracic esophagectomy with lymphadenectomy from Nov.1990 to Dec.2010 at the Cancer Hospital of Shantou University Medical College.The survival analysis was performed using Kaplan-Meier method.ResultsThe clinical symptoms,imaging and endoscopic features of PESC were similar to those of esophageal squamous cell carcinoma (ESCC).Of the 26 cases that received pre-operative endoscopic biopsy,only five cases were diagnosed as PESC,while the other 21 cases were misdiagnosed as ESCC.The mean follow-up time of this series was 25.3 months (0-123 months).34 patients died of the disease during the follow-up;7 were still alive and 1 was lost.The median survival time (MST) of the 41 patients was 13.0 months (95 ％ confidence interval 6.3-19.7),and the 6-,12-,24-,36-,and 60-month overall survival rates (OS) were 78.6 ％,57.5 ％,30.8 ％,23.7 ％,10.5 ％,respectively.ConclusionPESC is a rare disease with poor prognosis,and is prone to be misdiagnosed by endoscopic biopsy.Currently no standard treatment has been established.