Objective To evaluate the diagnostic value of pathological features of atypical membranous nephropathy (AMN). Methods Ninety - one patients with AMN diagnosed by renal biopsy during 2011 and 2017 were enrolled in this study. On the basis of M - type phospholipase A2 receptor (PLA2R) and thrombospondin type - 1 domain - containing 7A protein (THSD7A) by immunohistochemistry, patients were divided into AMN group (25 cases without PLA2R and THSD7A) and idiopathic membranous nephropathy (IMN) group (66 cases with positive PLA2R or THSD7A). The results of immunofluorescence (IF), light microscopy (LM) and electron microscopy (EM) of these two groups were compared, and the parameters with statistical difference were screened out in order to assess their value in the diagnosis of AMN in fourfold table. Results IF results showed that in AMN group the proportions of IgG deposition on capillary wall and mesangial area as well as positive otherIgG subclasses and complement C1q but negative IgG4 were significantly higher than those in IMN group (respectively, 56.0％ vs 12.1％ , 44.0％ vs 0, both P＜0.05). Their diagnostic specificities for AMN were 87.9％ and 100.0％, respectively. However, the positive rates of IgG accompanied with IgA and/or IgM, predominant IgG4 with other IgG subclasses and complement C1q in two groups were not significantly different (all P＞0.05). LM results showed that the proportions of false double track sign on basement membrane and fuchsinophilic proteins under epithelium, endothelium, basement membrane and mesangial region in AMN group were significantly higher than those in IMN group (respectively, 36.0％ vs 0, 44.0％ vs 1.5％, both P＜0.05). Their diagnostic specificities for AMN were 100.0％ and 98.5％ , respectively. However, the scores of mesangial cell proliferation of these two groups showed no significantly difference (P＞0.05). EM results showed that the rate of endothelial electron dense deposits in AMN group was significantly higher than that in IMN group (36.0％ vs 1.5％, P＜0.05), and its diagnostic specificity for AMN was 98.5％. Conclusions IgG deposition on both capillary wall and mesangial area, positive other IgG subclasses and C1q with negative IgG4, false -double contour sign, multi - site fuchsinophilic deposits and endothelial electron dense deposits may help for the AMN diagnosis in the absence of PLA2R and THSD7A related data.

Objective To investigate whether the clinical and pathological injury of kidney in IgA nephropathy (IgAN) patients with hypertension is associated with circadian blood pressure rhythm change, particularly with elevated nocturnal blood pressure (BP). Methods This study was a retrospective cross-sectional study. Clinic and renal histopathological injury data were obtained from 83 IgAN patients with hypertension. First, 24 h ambulatory BP monitoring (ABPM) data were analyzed. Second, all these IgAN patients were divided into two groups, elevated nocturnal BP group and nocturnal normotensive BP group, and the clinical and pathological differences between this two groups were analyzed. Third, logistic regression analysis was used to analyze the influencing factors of renal tubulointerstitial injury in IgAN patients with hypertension. At last, all these IgAN patients were divided into two groups according to the level of estimated glomerular filtration rate (eGFR), group of patients with eGFR≥60 ml·min-1·(1.73 m2)-1 and the other group with eGFR<60 ml·min-1·(1.73 m2)-1, and the 24 h ABPM data were compared. Results (1) The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension was 79.5％. (2) Compared with nocturnal normotensive BP group, patients in elevated nocturnal BP group had significantly higher levels of 24-hour urinary protein quantity and blood uric acid (both P<0.05), and lower eGFR and urine osmotic pressure clinically (both P<0.05). Index of interstitial fibrosis and tubular atrophy was significantly higher in nocturnal normotensive BP group (P<0.05), while the proportion of glomerular ischemia lesion was not significantly different between two groups. (3) Multivariate logistic regression analysis showed that elevated nocturnal BP was an independent risk factor for severe tubulointerstitial injury of IgAN (OR=1.113, 95％CI 1.038-1.192, P=0.002). (4) Compared with the group of eGFR≥60 ml·min-1·(1.73 m2)-1, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime SBP and DBP, nocturnal SBP and DBP were significantly higher in group of eGFR<60 ml·min-1·(1.73 m2)-1 (all P<0.05). Conclusion The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension is as high as 79.5％. Elevated nocturnal BP is associated with the severity of renal damage, and elevated nocturnal BP is an independent risk factor for severe tubulointerstitial injury in IgAN patients with hypertension. Therefore, 24 h ABPM should be emphasized, and elevated nocturnal BP should be well controlled to slow the progression of IgAN.

Inflammatory bowel disease refers to chronic inflammatory disorders that affect the gastrointestinal tract. Ubiquitination is an important protein post-translational modification. In recent years, the research of ubiquitination-deubiquitination system in the development of inflammatory bowel disease has become a hot spot. Up to now, the E3 ubiquitin ligases such as ring finger protein 183 (RNF183), RNF20, Itch and A20 were well studied in inflammatory bowel disease. RNF183 promotes the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα; RNF20 drives histone H2B monoubiquitylation, downregulates a panel of inflammation-associated genes; Itch inhibits IL-17-mediated colon inflammation by retinoid acid related orphan receptor γt ubiquitination; A20 has ubiquitinating-deubiquitinating activity to regulates colon inflammation. This article reviews the role and regulatory mechanism of RNF183, RNF20, Itch and A20 in the pathogenesis of inflammatory bowel disease.
Histones ; metabolism ; Humans ; Inflammatory Bowel Diseases ; physiopathology ; NF-kappa B ; metabolism ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination

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.

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 examine whether aldosterone contribute to obesity related glomerular disease. Methods C57BL/6J mice were randomly divided into three groups: a control group (low?fat?diet, n=10), a model group (high?fat?diet, n=10) and a intervention group (high?fat?diet, n=12). After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone (SPL).The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real?time PCR and Western blotting, respectively. Results Compared with the control group, body weight, kidney weight, Lee ’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up ? regulated (P<0.05); The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down?regulated in model group (P<0.05). Meanwhile, these changes were attenuated by SPL. Conclusion Aldosterone can participate in the process of obesity? related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.

Pin1 (peptidyl-prolyl cis-trans isomerase NIMA-interacting 1) belongs to peptidyl-prolyl cis-trans isomerase (PPIase) and is a novel promising anticancer target. Based on the lead structure of benzophenone, a series of novel diarylether derivatives containing a pyrimidine ring were designed and synthesized. The inhibitory activities on Pin1 of compounds 5a-5d and 6a-6i were evaluated by a protease-coupled enzyme assay. Of all the evaluated compounds, 6 compounds displayed inhibitory activities. Molecular docking was performed using FlexX algorithm to explore the binding mode of the active molecules.

Objective To explore the correlation of anticardiolipin antibody (ACL) and lupus nephritis (LN) glomerular microthrombi (GMT) in patients with systemic lupus erythematosus (SLE) and to analyze their clinical manifestations and renal pathological characteristics.Methods The clinical data of 126 LN patients treated at our hospital between January 2005 and October 2010 were retrospectively reviewed.The factors,including age,gender,the clinical manifestations in and outside of kidney were evaluated by multivariate Logistic regression analysis.Enzyme-linked immunosorbent assay (ELISA) was used to test the serum levels of ACL in all patients.Statistical analysis was conducted using x2 test and Logistic regression.Results ① All 126 patients were investigated.Thirty-eight LN patients had GMT.When compared with the LN-non-GMT group,the SLE disease activity index (SLEDAI),urinary protein quantity (24 h),serum creatinine,serum urea nitrogen,anti-dsDNA antibody (+),the incidence of severe hypertension,anemia,thrombocytopenia,arthritis were higher in the LN-GMT group (P＜0.01).Logistic regression analysis showed that SLEDAI (OR=2.486,95％CI 1.678-3.684,P=0.000),anemia (OR=4.628,95％CI 1.045～20.496,P=0.044) were correlated with GMT; ② The pathologic results of renal biopsy showed that GMT had an incidence of 30.2％ (n=38) in LN.As compared with the LN-non-GMT group,Wilcoxon test showed that the LN-GMT group suffered more severe greater renal pathological injuries (P=0.012).The pathological types of LN-non-GMT and LN-GMT groups were as follows:type Ⅳ (38％ vs 76％) and type Ⅲ (31％ vs 8％); ③ The positive rate of ACL was higher in the LN-GMT group than that in the LN-non-GMT group (n=23,61％ vs n=15,36％).The differences were statistically significant (P=0.018).Conclusion GMT is not rare in LN.SLEDAI,anemia and positive ACL are correlated with GMT,LN patients with concurrent GMT have more severe renal pathological changes.

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.

A novel series of sorafenib analogs containing 2-picolinyl hydrazide moiety were designed and synthesized. In vitro, most of synthesized compounds have antiproliferation activity on MDA-MB-231, ACHN, HepG2, Mia-PaCa-2 and SW1990 cell lines tested by MTT assay. It is worth noting that the antitumor activities of compounds 2c, 2d and 2f are more potent than that of sorafenib on pancreatic cancer cells Mia-PaCa-2 and SW1990, and the activities of compounds 3f and 3g are 2-3 times than that of sorafenib on human hepatocellular carcinoma HepG2 cell line.