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Tumor segmentation using magnetic resonance imaging (MRI) plays a significant role in assisting brain tumor diagnosis and treatment. Recently, U-Net architecture with its variants have become prevalent in the field of brain tumor segmentation. However, the existing U-Net models mainly exploit coarse first-order features for tumor segmentation, and they seldom consider the more powerful second-order statistics of deep features. Therefore, in this work, we aim to explore the effectiveness of second-order statistical features for brain tumor segmentation application, and further propose a novel second-order residual brain tumor segmentation network, i.e., SoResU-Net. SoResU-Net utilizes a number of second-order modules to replace the original skip connection operations, thus augmenting the series of transformation operations and increasing the non-linearity of the segmentation network. Extensive experimental results on the BraTS 2018 and BraTS 2019 datasets demonstrate that SoResU-Net outperforms its baseline, especially on core tumor and enhancing tumor segmentation, illuminating the effectiveness of second-order statistical features for the brain tumor segmentation application.

Purpose To develop and validate a nomogram model to predict the occurrence of acute kidney disease (AKD) after nephrectomy. Patients and methods A retrospective cohort including 378 patients with renal cell carcinoma (RCC) who had undergone radical or partial nephrectomy between March 2013 and December 2017 at the First Affiliated Hospital of Zhengzhou University was analyzed. Of these, patients who had undergone surgery in an earlier period of time formed the training cohort (n=265) for nomogram development, and those who had undergone surgery thereafter formed the validation cohort (n=113) to confirm the model's performance. The incidence rate of AKD was measured. Univariate and multivariate logistics regression analysis was used to estimate the independent risk factors associated with AKD. The independent risk factors were incorporated into the nomogram. The accuracy and utility of the nomogram were evaluated by calibration curve and decision curve analysis, respectively. Results Overall, AKD occurred in 27.5% and 28.3% of patients in the training and validation cohorts, separately. The final nomogram included surgery approach, Charlson comorbidity index (CCI), and the decrement of eGFR. This model achieved good concordance indexes of 0.78 (95% CI=0.71-0.84) and 0.76 (95% CI=0.67-0.86) in the training and validation cohorts, respectively. The calibration curves and decision curve analysis (DCA) demonstrated the accuracy and the clinical usefulness of the proposed nomogram, separately. Conclusion The nomogram accurately predicts AKD after nephrectomy in patients with RCC. The risk for patients' progress into AKD can be determined, which is useful in guiding clinical decisions.

The prevalence of kidney diseases is emerging as a public health problem. Stem cells (SCs), currently considered as a promising tool for therapeutic application, have aroused considerable interest and expectations. With self-renewal capabilities and great potential for proliferation and differentiation, stem cell therapy opens new avenues for the development of renal function and structural repair in kidney diseases. Mounting evidence suggests that stem cells exert a therapeutic effect mainly by replacing damaged tissues and paracrine pathways. The benefits of various types of SCs in acute kidney disease and chronic kidney disease have been demonstrated in preclinical studies, and preliminary results of clinical trials present its safety and tolerability. This review will focus on the stem cell-based therapy approaches for the treatment of kidney diseases, including various cell sources used, possible mechanisms involved, and outcomes that are generated so far, along with prospects and challenges in clinical application.

Background This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a central Chinese urban population. Methods From December 2017 to June 2018, a total of 5231 subjects were randomly enrolled from 3 communities in 3 districts of Zhengzhou. CKD was defined as estimated glomerular filtration rate (eGFR) 2 or urinary albumin to creatinine ratio ≥ 30 mg/g (albuminuria). Diabetic subjects with systolic blood pressure > 140 mmHg, albuminuria or an eGFR less than 60 mL/min/1.73 m2 were classified as having DKD. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urine specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and sex-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduced renal function were analyzed by binary and ordinal logistic regression. Results The overall adjusted prevalence of CKD was 16.8% (15.8–17.8%) and that of DKD was 3.5% (3.0–4.0%). Decreased renal function was detected in 132 participants (2.9, 95% confidence interval [CI]: 2.5–3.2%), whereas albuminuria was found in 858 participants (14.9, 95% CI: 13.9–15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9–8.6%) and that of albuminuria was 45.3% (95% CI = 40.4–50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1–52.9%). The results of the binary and ordinal logistic regression indicated that the factors independently associated with a higher risk of reduced eGFR and albuminuria were older age, sex, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. Conclusions Our study shows the current prevalence of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

Purpose Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians. Patients and methods In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted. Results The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p

Previous studies have shown a significant correlation between depression, resilience, self-efficacy, self-esteem and hope among schizophrenia patients, but few studies have examined the mechanisms among these factors. This study aimed to analyse the relationships among resilience, self-efficacy, self-esteem and hope as influencing factors of depression in schizophrenia patients. A cross-sectional study was conducted, and 361 schizophrenia patients were recruited. They were interviewed about their self-efficacy, self-esteem, hope, resilience and depressive symptoms. A structural equation model was used to examine the direct and indirect associations between them. The global model showed good model fit and the structural equation model revealed that the direct pathway of resilience on depression was significant, and the indirect pathway of self-efficacy, self-esteem and hope on depression via resilience was also significant. Notably, self-efficacy, self-esteem and hope did not directly affect depressive symptoms. These findings support the mediating model of self-efficacy, self-esteem and hope relevant to the depressive symptoms of schizophrenia patients in China, in which resilience plays a pivotal role. These findings elucidate the factors which may be associated with depressive symptoms and imply that enhancing resilience in people with schizophrenia could be beneficial. Moreover, studies with detailed longitudinal assessments are necessary to confirm these findings.

Diabetic nephropathy is considered one of the most common microvascular complications of diabetes and the pathophysiology involves multiple factors. Progressive diabetic nephropathy is believed to be related to the structure and function of the tubular epithelial cells in the kidney. However, the role of lysine acetylation in lesions of the renal tubular epithelial cells arising from hyperglycemia is poorly understood. Consequently, in this study, we cultured mouse renal tubular epithelial cells in vitro under high glucose conditions and analyzed the acetylation levels of proteins by liquid chromatography-high-resolution mass spectrometry. We identified 48 upregulated proteins and downregulated 86 proteins. In addition, we identified 113 sites with higher acetylation levels and 374 sites with lower acetylation levels. Subcellular localization analysis showed that the majority of the acetylated proteins were located in the mitochondria (43.17%), nucleus (28.57%) and cytoplasm (16.19%). Enrichment analysis indicated that these acetylated proteins are primarily associated with oxidative phosphorylation, the citrate cycle (TCA cycle), metabolic pathways and carbon metabolism. In addition, we used the MCODE plug-in and the cytoHubba plug-in in Cytoscape software to analyze the PPI network and displayed the first four most compact MOCDEs and the top 10 hub genes from the differentially expressed proteins between global and acetylated proteomes. Finally, we extracted 37 conserved motifs from 4915 acetylated peptides. Collectively, this comprehensive analysis of the proteome reveals novel insights into the role of lysine acetylation in tubular epithelial cells and may make a valuable contribution towards the identification of the pathological mechanisms of diabetic nephropathy.

BackgroundThere is growing evidence to demonstrate that the epigenetic regulation of immune characteristics, especially for N6-methyladenosine (m6A) RNA methylation. However, how m6A methylation is involved in lupus nephritis (LN) is still unclear. This study aimed to determine the role of m6A RNA methylation and their association with the immune microenvironment in LN.MethodsIn total, 87 glomeruli (73 LN, 14 living healthy donors), 110 tubulointerstitium (95 LN, 15 living healthy donors), and 21 kidney whole tissue samples (14 LN, 7 controls) were included in our research to evaluate the expression levels of m6A regulators. CIBERSORT was used to assess the abundance of infiltrating immunocytes. The m6A regulator gene signature for LN was identified using LASSO-logistic regression and verified with external data. Consensus clustering algorithms were used for the unsupervised cluster analysis of m6A modification patterns in LN. Single-sample gene-set enrichment analysis and gene set variation analysis algorithms were employed to assess the activity of immune responses and other functional pathways. Weighted gene co-expression network analysis and protein-protein interaction networks were used to identify m6A methylation markers. Lastly, the Nephroseq V5 tool was used to analyze the correlation between m6A markers and renal function.ResultsWe found that the expression of m6A regulators was more significantly different in the glomeruli in LN compared with tubulointerstitium and whole kidney tissue. We established an m6A regulator signature, comprised of METTL3, WTAP, YTHDC2, YTHDF1, FMR1, and FTO, that can easily distinguish LN and healthy individuals. Two distinct m6A modification patterns based on 18 m6A regulators were determined, with significant differences in m6A regulator expression, immune microenvironment, biological functional pathways, and clinical characteristics. Activated NK cells, most immune responses, and HLA genes had strong correlations with m6A regulators. Seven m6A markers were identified and demonstrated a meaningful correlation with GFR, indicating that they are potential prognostic biomarkers.ConclusionThis study emphasized that m6A RNA methylation and the immune microenvironment are closely linked in LN. A better understanding of m6A modification patterns provide a basis for the development of novel therapeutic options for LN.

Huanhuan Zhao,1– 5,* Lulu Liang,1– 5,* Shaokang Pan,1 Zhenjie Liu,1 Yan Liang,1 Yingjin Qiao,1 Dongwei Liu,1– 5 Zhangsuo Liu1– 5 1Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Research Center for Kidney Disease, Zhengzhou, 450052, Henan Province, People’s Republic of China; 4Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, People’s Republic of China; 5Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhangsuo Liu; Dongwei LiuDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, People’s Republic of ChinaTel +86-0371-66295921Email Lzs58055@163.com; dongweiliu01@163.comPurpose: Acute kidney injury is very common in hospitalized patients and carries a significant risk of mortality. Although timely intervention may improve patient prognosis, studies on the development of acute kidney disease in patients with acute kidney injury remain scarce. Thus, we constructed a prediction model to identify patients likely to develop acute kidney disease.Patients and Methods: Among 474 patients screened for eligibility, 261 were enrolled and randomly divided into training (185 patients) and independent validation cohorts (76 patients). Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were used to select features and build a nomogram incorporating the selected predictors: diabetes, anemia, oliguria, and peak creatinine. Calibration, discrimination, and the clinical usefulness of the model were assessed using calibration plots, the C-index, receiver operating characteristic curves, and decision curve analysis.Results: Diabetes was significantly associated with the presence of AKD. Peak creatinine, oliguria, and anemia also contributed to the progression of acute kidney injury. The model displayed good predictive power with a C-index of 0.834 and an AUC of 0.834 (95% confidence interval (CI): 0.773– 0.895) in the training cohort and a C-index of 0.851 and an AUC of 0.851 (95% CI: 0.753– 0.949) in the validation cohort. The calibration curves also showed that the model had a medium ability to predict acute kidney disease risk. Decision curve analysis showed that the nomogram was clinically useful when interventions were decided at the possibility threshold of 22%.Conclusion: This novel prediction nomogram may allow for convenient prediction of acute kidney disease in patients with acute kidney injury, which may help to improve outcomes.Keywords: diabetes mellitus, acute kidney injury, anemia, oliguria, nomogram

Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.

Brain tumor segmentation methods using deep neural networks have recently achieved significant performance breakthroughs. However, the existing brain tumor segmentation networks are directly implemented on whole brain images, resulting in possibly reduced segmentation performance due to the disturbance of background regions. To solve this problem, inspired by the Mask R-CNN, a novel brain tumor segmentation model called BrainSeg R-CNN is proposed in this work, which classifies the brain tumor areas and boundaries based on the detected region of interest in an end-to-end manner to achieve segmentation result. Also, an effective feature extraction strategy is presented in BrainSeg R-CNN, which in detail extracts various kinds of information from separate channels for each modality and immediately adopts a cross-connection operator to realize the information transmission among different channels. Moreover, concatenation and add calculation are integrated to improve the fusion efficiency of multi-scale features from brain tumor images. Additionally, a multi-weighted and multi-task loss function which fully considers tumor size and overlap label is introduced, significantly improving the segmentation performance. Experimental results on BraTS 2017 dataset demonstrate that our BrainSeg R-CNN obtains competitive performance with state-of-the-arts.

The impact of ambient particulate matter (PM) on public health has become a great global concern, which is especially prominent in developing countries. For health purposes, PM is typically defined by size, with the smaller particles having more health impacts. Particles with a diameter 2.5. Initial research studies have focused on the impact of PM2.5 on respiratory and cardiovascular diseases; nevertheless, an increasing number of data suggested that PM2.5 may affect every organ system in the human body, and the kidney is of no exception. The kidney is vulnerable to particulate matter because most environmental toxins are concentrated by the kidney during filtration. According to the high morbidity and mortality related to chronic kidney disease, it is necessary to determine the effect of PM2.5 on kidney disease and its mechanism that needs to be identified. To understand the current status of PM2.5 in the atmosphere and their potential harmful kidney effects in different regions of the world this review article was prepared based on peer-reviewed scientific papers, scientific reports, and database from government organizations published after the year 1998. In this review, we focus on the worldwide epidemiological evidence linking PM2.5 with chronic kidney disease and the effect of PM2.5 on the chronic kidney disease (CKD) progression. At the same time, we also discuss the possible mechanisms of PM2.5 exposure leading to kidney damage, in order to emphasize the contribution of PM2.5 to kidney damage. A global database on PM2.5 and kidney disease should be developed to provide new ideas for the prevention and treatment of kidney disease.

Background: Previous studies have suggested that serum total bilirubin (STB) levels are associated with heightened chronic kidney disease (CKD) and mortality in both the general population and nephropathy patients. However, these results remain inconsistent. The aim of our study was to investigate whether STB was a predictor for progression of CKD and mortality by meta-analysis.Methods: We performed a systematic literature search in PubMed, Web of Science, MEDLINE, EMBASE, Google Scholar, and Cochrane Library's database up to June 30, 2019. Pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) were extracted for the highest vs. lowest category STB levels within the physiological range, and a random-effects model was applied to calculate the dose–response relationships. A pooled hazard ratio (HR) was used to investigate the association between STB levels and mortality in dialysis patients.Results: A total of 16 studies, wherein participants were followed from 21 months to 7 years, were eligible for inclusion in the study. For the categorized STB, 11 studies with 41,188 participants were identified and analyzed. Patients with the highest STB levels were associated with a lower risk of CKD (RR = 0.64; 95% CI 0.55–0.73) compared to those with the lowest STB levels. Furthermore, based on seven studies, a pooled RR of 0.89, 95% CI (0.80–0.99) was observed for the continuous STB levels (per 0.2 mg/dL increase). Four studies that included 51,764 participants illustrated that there was no association between STB levels and all-cause mortality (HR = 0.77; 95% CI 0.42–1.41). A prominent negative linear relationship (X2 = 14.70; P = 0.0001) was found between STB levels and risk of CKD. Subgroup analyses showed that there were no significant differences in the subgroup adjustment factor except for sample size.Conclusions: Elevated STB levels within a physiological range are associated with lower risk of CKD regardless of the study characteristics and coincide with a liner dose–response relationship. However, whether high STB levels are a protective factor against mortality remains inconclusive. Large-scale randomized controlled trails are needed to target STB levels for predicting renal outcomes.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus. It is the most frequent cause of end-stage renal disease with no definitive therapy available so far. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are nano- and micron-sized heterogeneous vesicles that can be secreted by almost all cell types. Importantly, EVs contain many biologically active materials, such as RNAs, DNAs, proteins, and lipids, from their parental cells, which can be transported to their recipient cells to mediate intercellular communication and signaling. Accumulating studies demonstrated that EVs, mainly exosomes and microvesicles, participated in the pathophysiological process of DN. Recently emerging studies also found that the contents of EVs in the urine (miRNAs, mRNAs, and proteins) could be used as potential biomarkers for DN. Therefore, in this mini-review, the generation, isolation methods, and biological function of EVs were introduced, and then the current information about the mechanism and the diagnostic value in the development of DN was summarized. Moreover, the review also discussed the future challenges of exploring the role of EVs in kidney disease.

Podocyte apoptosis is considered as the important element that promotes the development and progress of membranous nephropathy (MN). Unfortunately, the underlying mechanism of podocytes apoptosis in MN remains elusive. We compared the renal expressions of miR-130a-5p and M-type phospholipase A2 receptor (PLA2R) between MN patients (n = 30) and 30 controls by qRT-PCR and western blot, respectively. The podocyte damage model in vitro was established by angiotensin II (Ang II, 100 nmol/L) exposure for 24 h. Interaction between miR-130a-5p and PLA2R was determined using dual-luciferase reporter gene assay. MN mice were induced by intravenous injection of cBSA. In this study, miR-130a-5p expression was significantly decreased both in the renal biopsy specimens from MN patients and podocyte cell line AB8/13 following stimulation of Ang II. Overexpressed miR-130a-5p in AB8/13 cells significantly attenuated the Ang II induced-apoptosis in vitro. In contrast, down-regulated miR-130a-5p induced podocyte apoptosis. PLA2R was identified as the target of miR-130a-5p in AB8/13 cells. And up-regulated or down-regulated PLA2R could obviously attenuate the effect of miR-130a-5p overexpression or knockdown on the apoptosis of AB8/13 cells. Furthermore, it was also observed that overexpressed miR-130a-5p by miR-130a-5p agomir could obviously alleviate renal injury in MN mice. In conclusion, decreased miR-130a-5p was contributed to the pathological mechanism of MN through increasing PLA2R expression, which induced podocyte apoptosis.

Background: Type 2 diabetes (T2DM) patients are susceptible to Helicobacter pylori (HP), and it has been reported that the occurrence of proteinuria is associated with HP infection in T2DM patients; however, this view remains controversial. This meta-analysis aimed to explore the association between HP infection and the occurrence of proteinuria in T2DM patients. In addition, we hope to provide some recommendations to readers in clinical or related fields. Methods: Our meta-analysis was conducted with the methodology of the Cochrane Collaboration. Search strategies were formulated by relevant professionals. Case–control studies that compared the occurrence of proteinuria in T2DM patients with and without HP infection were involved in our meta-analysis. Relevant English or Chinese studies were searched on online databases before 2018, including PubMed, the Cochrane library, Medline, Google Scholar, the China National Infrastructure, and Wanfang database. The search strategies were "diabetic proteinuria, diabetic microalbuminuria, diabetic albuminuria, diabetic kidney disease, diabetic renal dysfunction, diabetic renal disease, diabetic nephropathy, diabetic complications, and diabetic mellitus, combined with HP." The quality of these involved articles was separately assessed by two investigators using the Newcastle–Ottawa Scale (NOS). Odds ratios (ORs) and associated 95% confidence intervals (CIs) were extracted and pooled using fixed-effects models. Results: Seven studies involving 1029 participants were included. The quality of these seven articles was all above five stars as assessed by NOS, and there was no significant publication bias in our meta-analysis. We found that T2DM patients with HP infection had a 2.00 times higher risk of the occurrence of proteinuria than patients without HP infection (OR: 2.00, 95% CI: 1.48–2.69). Conclusions: Our analysis showed that HP infection was associated with the occurrence of proteinuria in T2DM patients. HP radical surgery might be a therapeutic option for protecting kidney function in patients with T2DM. Key words: Helicobacter pylori; Kidney; Meta-Analysis; Proteinuria; Type 2 Diabetes

Thyroid carcinoma metastasis is the main reason for treatment failure; therefore, understanding the regulatory mechanisms of thyroid carcinoma metastasis is critical to treat patients with thyroid carcinoma. The present study aimed to investigate the role of AHNAK Nucleoprotein 2 (AHNAK2) in thyroid carcinoma metastasis. AHNAK2 was found to be upregulated in thyroid carcinoma tissues, especially in metastatic thyroid carcinoma tissues. Patients with high AHNAK2 expression had poor prognosis. AHNAK2 knockdown inhibited thyroid carcinoma migration, invasion, and metastasis. Mechanistic analysis showed that AHNAK2 knockdown reduced thyroid carcinoma progression by inhibiting nuclear factor kappa B (NF-κB) pathway activity. The results identified a novel target to treat metastatic thyroid carcinoma.

// Dongwei Liu 1 , Chang Peng 1 , Zhengxuan Jiang 1, * and Liming Tao 1, * 1 Department of Ophthalmology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, PR China * These authors have contributed equally to this work Correspondence to: Liming Tao, email: taolimingchina@163.com Keywords: cyclooxygenase 2; angiogenesis; pterygium; immunohistochemical; VEGF Received: May 17, 2017 Accepted: July 25, 2017 Published: November 09, 2017 ABSTRACT In present study, we are to test the relationship between cyclooxygenase 2 (COX-2) and angiogenesis in pterygium tissues from a group of Chinese patients. Here forty-five primary pterygium tissues and twenty-three normal bulbar conjunctival tissues were obtained during ophthalmologic surgeries. The primary pterygium samples were treated for the immunohistochemical evaluation of COX-2, CD31 and vascular endothelial growth factor (VEGF) antibodies for different tissues. In order to evaluate the relationship between COX-2 and neovascularization, a statistical analysis was performed using the SPSS 13.0 statistical software package. As results, in our study, 36 (80%) of the primary pterygia samples were found to be positive for COX-2 staining, which was not found in the normal conjunctivas. The density of the microvessels (MVD) was significantly increased in the COX-2 positive patients when compared to the COX-2 negative ones (19.06 ± 1.84 vs.10.44 ± 2.98, P=1.36×10 -5 ) in the pterygia cases. In the group that was positive for COX-2, there were 39 (86.7%) samples with VEGF expression. Furthermore, the staining of both COX-2 and VEGF was localized to the lower and middle layers of the epithelium and the endothelial cells of the microvessels. When analyzed the relation between them, the expression of COX-2 showed a significant correlation with the MVD (P = 4.02×10 -4 ) and VEGF (p = 2.72×10 -4 ). In conclusion, the present study showed that COX-2 may play an important role in stimulating the angiogenesis of pterygium in concert with VEGF.

Background : Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and is one of the most common and serious complications of diabetes mellitus (DM). SIRT1 and TTP are two important protective factors in DN, however, the regulatory relationship between SIRT1 and TTP and the underneath mechanism are interesting but still unclear. Identifying the key factors that regulate SIRT1 or TTP may be of great value to the understanding and treatment of the DN. Methods : in this study, through systematic experimental methods, we found that the expression of miR-138 was significantly up-regulated in DN clinical patients samples, and our experimental results suggested that miR-138 could bind the 3’UTR of SIRT1 and inhibit its expression in both cultured podocytes and db/db mice kidney tissues. Results : furthermore, our in vitro and in vivo date also indicated miR-138 could target SIRT1 and affect TTP through p38 pathway. And down-regulation of miR-138 attenuated podocyte injury and showed some extend of therapeutic effects in DN mice models. Conclusion : our findings reveal that the regulatory axis of miR-138-SIRT1-p38-TTP might play a key role in DN. We believe these findings may be of some value for deepening the understanding of DN and may serve as a reference for future treatment of this disease.

Background The underlying mechanism between hope and quality of life is as yet unknown. We aim to examine the potential mediating effect of depression and resilience and the moderated effect of sex in this well-established association. Methods Two hundred seven patients diagnosed with schizophrenia were administered a questionnaire battery that measured hope, depression, resilience and QOL. A multiple mediation model was used to examine the mediating effect of resilience and depression on the association between hope and QOL. A subgroup analysis was performed and a moderated mediation model was examined to find and test the moderated effect of sex on the mediation model. We used Mplus to perform moderation and mediation analyses so that the mediators and moderator could function together in the same model. Result Sex was the moderator on the direct path between hope and QOL. The relationship between hope and QOL was mediated by resilience and depression in both sexes. When compared with female patients, the effect of hope on QOL was completely mediated by resilience and depression in males. In female patients, the model was partially mediated, and the direct effect of hope on QOL was significantly negatively correlated with the level of hope. Conclusion We present a conceptual model containing the mediated effects of resilience and depression and the moderated effect of sex between hope and QOL, which we believe facilitates the understanding of these associations. This model should be useful in the formulation of strategies to improve QOL.

Diabetic nephropathy (DN) is one of the most serious chronic kidney diseases and the major cause of end-stage renal failure worldwide. The underlying mechanisms of DN are complex and required to be further investigated. Both innate immunity and renin-angiotensin system (RAS) play critical roles in the pathogenesis of DN. Except for traditional functions, abnormally regulated RAS has been proved to be involved in the inflammatory process of DN. Toll-like receptor 4 (TLR4) is the most deeply studied pattern recognition receptor in the innate immune system, and its activation has been reported to mediate the development of DN. In this review, we aim at discussing how dysregulated RAS affects TLR4 activation in the kidney that contributes to the exploration of the pathogenesis of DN. Understanding the interplay of RAS and TLR4 in inducing the progression of DN may provide new insights to develop effective treatments.

We conducted a cross-sectional survey including 23869 participants and aimed to measure the prevalences of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a Chinese rural population. CKD and DKD status was defined according to the combination of estimated glomerular filtration rate (eGFR) and presence of albuminuria Participant completed a questionnaire involving life-style and relevant medical history, and the blood and urinary specimen were taken. The age- and gender- adjusted prevalences of CKD and DKD were calculated and risk factors associated with the presence of CKD and DKD were analyzed by logistic regression. The overall prevalence of CKD was 16.4% (15.9–16.8%) and of DKD was 2.9% (2.7–3.1%). In participants with diabetes, the overall prevalence of CKD was 35.5% (95% CI = 33.7–37.3%). Factors independently associated with renal damage were age, gender, education, personal income, alcohol consumption, overweight, obesity, diabetes, hypertension and dyslipidemia. Our study shows current prevalences of CKD and DKD in Chinese rural residents. Further researches could identify potential factors explaining the observed differences and implement the interventions to relieve the high burden of CKD and DKD in rural population.

Exosomes, a major type of extracellular vesicles (EVs), are nanoscale vesicles excreted by almost all cell types via invagination of the endosomal membrane pathway. Exosomes play a crucial role in the mediation of intercellular communication both in health and disease, which can be ascribed to their capacity to be transported to neighboring or distant cells, thus regulating the biological function of recipient cells through cargos such as DNA, mRNA, proteins and microRNA. Diabetic nephropathy (DN) is a serious microvascular complication associated with diabetes mellitus as well as a significant cause of end-stage renal disease worldwide, which has resulted in a substantial economic burden on individuals and society. However, despite extensive efforts, therapeutic approaches that prevent the progression of DN do not exist, which implies new approaches are required. An increasing number of studies suggest that exosomes are involved in the pathophysiological processes associated with DN, which may potentially provide novel biomarkers and therapeutic targets for DN. Hence, this review summarizes recent advances involving exosome mechanisms in DN and their potential as biomarkers and therapeutic targets. Abbreviation.Unlabelled TableEVsextracellular vesiclesDNdiabetic nephropathySGLT2sodium-glucose co-transporter 2GLP-1glucagon-like peptide-1MVBsmultivesicular bodiesESRDend-stage renal diseaseGBMglomerular basement membraneGECsglomerular endothelial cellsGMCsglomerular mesangial cellsEMTepithelial-mesenchymal transitionPTECsproximal tubular epithelial cellsNF-κBnuclear factor κBTGF-βtransforming growth factor-βVEGFvascular endothelial growth factorECMextracellular matrixmTORmammalian target of rapamycinAMPKadenosine monophosphate- activated protein kinaseMSCsmesenchymal stem cellsADSCsadipose-derived stem cellsIRinsulin resistancehUSCshuman urine-derived stem cellsPPARγperoxisome proliferator-activated receptor γATMadipose tissue macrophagesGLUT4glucose transporter 4

Membranous nephropathy (MN) is the most common primary glomerular disease (PGD) in the world. Currently, MN still lacks specific diagnostic markers and effective treatment strategy. It is speculated that the occurrence of MN is mainly related to environmental and genetic factors. The pathological manifestations of MN patients are diverse, significant differences in response to treatment options, and more reports on young MN patients suggest the importance of genes in the pathogenesis and diagnosis of MN. We will propose a novel perspective on the important role of genes in the pathogenesis of MN baced on the latest research.

Subject The aim of this study was to investigate whether vitamin D plays a protective role in podocyte injury induced by autoantibodies purified from the serum of patients with lupus nephritis (LN) via reducing aberrant autophagy. Methods Autophagic activities of renal tissues of patients with LN were evaluated under transmission electronic microscope (TEM). Immunoglobulin G (IgG) from patients with LN was purified to induce human podocyte injury, and the role of vitamin D in injury was observed. Podocytes were observed under TEM, autophagic activity was evaluated by western blot analysis and quantitative real-time polymerase chain reaction, and mRFP-GFP-LC3B adenovirus was infected into human podocytes in vitro. Results Significantly higher autophagic levels were observed in patients with LN (P

Aim The current standard treatment for IgA nephropathy relies on steroid and/or immunosuppressive therapy and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB). This study examines the benefits and safety of combining valsartan with clopidogrel and leflunomide as a treatment for progressive IgA nephropathy. Methods Patients with primary IgA nephropathy, confirmed by renal biopsy, were recruited for this study. Patients were separated into four groups (n = 42 each) after 2 months of run-in period of valsartan treatment. All patients were treated with valsartan alone (Group 1) or valsartan and either clopidogrel (Group 2) or leflunomide (Group 3) or both clopidogrel and leflunomide (Group 4). Each group was followed up for their next 24 months for 24 h urinary protein excretion, serum creatinine and estimated glomerular filtration rate (eGFR) to assess the effect of the treatment. Adverse effects were recorded concurrently to evaluate the safety of the treatment. Results Of all 168 patients, 107 were males and 61 were females, with an average age of 33.8 ± 8.79 years. Baseline characteristics were comparable among the four groups (P > 0.05) prior to the experimental treatment. There was a significant (P

BackgroundTo date, cognitive–behavioural therapy (CBT) trials have primarily focused on clinical recovery; however, personal recovery is actually the fundamental aspect of the recovery process. The aim of this study was to summarise and synthesise the existing evidence regarding the effectiveness of CBT for personal recovery in patients with schizophrenia.AimThis study aimed to determine the effectiveness of CBT for personal recovery in patients with schizophrenia.MethodsA systematic search of the literature in PsycINFO, PubMed, Cochrane (CENTRAL), Embase and Web of Science (SCI) was conducted to identify randomised controlled trials reporting the impact of CBT interventions on personal recovery in patients with schizophrenia. The estimated effect sizes of the main study outcomes were calculated to estimate the magnitude of the treatment effects of CBT on personal recovery. We also evaluated the CBT’s effect size at the end-of-treatment and long-term (follow-up) changes in some aspects of personal recovery.ResultsTwenty-five studies were included in the analysis. The effect of CBT on personal recovery was 2.27 (95% CI 0.10 to 4.45; I2=0%; p=0.04) at post-treatment and the long-term effect size was 2.62 (95% CI 0.51 to 4.47; I2=0%; p=0.02). During the post-treatment period, the pooled effect size of CBT was 0.01 (95% CI −0.12 to 0.15; I2=33.0%; p>0.05) for quality of life (QoL), 0.643 (95% CI 0.056 to 1.130; I2=30.8%; p2=40%; p=0.02) for hopelessness and 1.85 (95% CI 0.69 to 3.01; I2=41%; pConclusionsCBT is an effective therapy with meaningful clinical effect sizes on personal recovery and some aspects of personal recovery of schizophrenia after treatment. However, the effect is relatively immediate and rapidly decreases as time progresses. Therefore, in the future, more studies should focus on the mechanism of CBT for personal recovery and the factors that influence the long-term effects of CBT.Trial registration numberCRD42018085643.

AIM To assess the prognostic implications of serum uric acid levels on patients with IgA nephropathy in a longitudinal 8-year follow-up study and to identify an association between serum uric acid levels and the clinical and pathological phenotypes of IgA nephropathy. SUBJECTS AND METHODS We reviewed the files of all consecutive patients with IgA nephropathy treated at our hospital between 2001 and 2009. Analyses were performed to investigate the association between the level of serum uric acid and both clinical and pathological phenotypes of IgA nephropathy. Prognosis was assessed based on follow-up data. RESULTS At the same glomerular filtration rate (GFR), there was no significant difference in the levels of 24 hours proteinuria, blood urea nitrogen (BUN), and serum creatinine between the two groups with different levels of serum uric acid (p > 0.05). The prevalence of glomerular sclerosis as well as the scores of tubulointerstitial and vascular injury was greater in patients with high serum uric acid levels compared to patients with normal levels of serum uric acid (p < 0.05). At the end of the follow-up period, patients with high serum uric acid levels had a higher prevalence of reduced GFR and end stage renal disease (ESRD) than those with normal serum uric acid levels (40.82 vs. 15.70% and 64.71 vs. 35.00%, respectively; p < 0.05). CONCLUSIONS The serum uric acid level in patients with IgA nephropathy affects the pathophysiology and prognosis of the disease. We also identified a correlation between hyperuricemia and a higher risk of renal end points.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and will lead some unfavorable outcomes such as end-stage renal disease. The efficacy of tonsillectomy remains controversial in both Asian and Caucasian ethnicity. Our meta-analysis was aiming at exploring its long-term efficacy and providing further evidences for clinical treatment.Prospective and retrospective studies that compared the rate of clinical remission and/or end-stage renal disease in IgAN patients who applied tonsillectomy were involved in our meta-analysis. The online databases we searched were PubMed, Embase, Cochrane Library, and Web of Science RESULTS: Nineteen studies with a total of 3483 participants are involved in our meta-analysis. It is found that treatment of tonsillectomy is significantly associated with a higher rate of clinical remission (15 studies, 3059 participants; pooled OR 3.30, 95 % CI 2.47-4.40). Meanwhile, tonsillectomy shows positive effect on refraining from developing end-stage renal disease (9 studies, 1804 participants; pooled OR 0.33, 95 % CI 0.16-0.69). In following two subgroup analyses, we integrate studies with more than 5 years of follow-up from clinical remission group and end-stage renal disease group. Both of them show that tonsillectomy has favorable long-term efficacy, pooled OR 3.37 (95 % CI 2.68-4.24) and 0.20 (95 % CI 0.12-0.33), respectively.Long-term efficacy of tonsillectomy indicates that this treatment is helpful in inducing clinical remission and inhibiting development of end-stage renal disease in patients with IgAN and should be considered for addition into standard clinical treatment.

BackgroundThe importance of circulating antibodies as biomarkers of kidney disease has recently been recognized. However, no study has systematically described the methodology of sample preparation and storage regarding antibodies as biomarkers of kidney disease. It remains unknown whether repetitive freeze-thaw cycles, physical disturbances, storage at different temperatures or for different periods of time, or haemolytic or turbid serum samples affect antibody measurements. The aim of this study was to investigate the stabilities of antibodies associated with kidney disease in serum samples under various relevant clinical and research conditions.MethodsWe stored serum samples in the following different conditions: repetitive freeze-thaw cycles (1, 6 or 12 times), long-term storage (7 or 12 months at −80 °C), physical disturbance (1 or 8 h), and storage at 4 °C (1, 3 or 6 weeks) and room temperature (1 or 7 days). The stabilities of the anti-phospholipase A2 receptor (anti-PLA2R), anti-glomerular basement membrane, anti-myeloperoxidase and anti-proteinase 3 antibodies were evaluated with enzyme-linked immunosorbent assays (ELISA).ResultsWe found that repetitive freeze-thaw cycles did not have a significant effect on the stabilities of the abovementioned antibodies in clear serum samples. The ELISA readings of haemolytic and turbid serum samples tended to increase and decrease, respectively. Neither long-term storage at −80 °C nor physical disturbance had a significant effect on anti-PLA2R antibody stability in sealed serum samples. The concentrations of most of these antibodies increased in unsealed serum samples that were stored at 4 °C for more than 6 weeks or at room temperature for more than 7 days.DiscussionOur findings revealed that the abovementioned circulating antibodies that are used as biomarkers for kidney disease had stable physicochemical properties, structures and immunoreactivities such that they were not influenced by repetitive freeze-thaw cycles, physical disturbances or long-term storage at −80 °C. However, the ELISA readings tended to change for haemolytic, turbid and unsealed serum samples.

Aim: Chronic kidney disease (CKD) poses a serious public health problem worldwide. Population-based studies determining the prevalence of this disease in China have been limited in several large developed cities. In the present study, a population-based screening study in Henan, a representative province in Central China, was conducted in order to quantify the prevalence of CKD and identify the associated risk factors for this disease in a population of developing areas of China. Methods: Residents (n = 4156) over 40 years old in four major cities of Henan Province were interviewed and their albuminuria, reduced renal function, haematuria and blood pressure were measured. Associations between age, components of metabolism syndrome and indicators of CKD were examined. Results: Among these subjects, the prevalence rates of albuminuria, haematuria and reduced renal function were 4.51%, 6.28% and 1.53%, respectively. Approximately 10.49% of the subjects had at least one indicator of kidney damage. The awareness rate of this disease in subjects with CKD was only 9.50%. Hypertension, diabetes and hyperuricaemia were three independent risk factors for CKD. Conclusion: The high prevalence and low awareness of CKD in the studied population suggest that CKD is a severe public health problem in Central China. Effectively preventive and therapeutic interventions are needed.

Objective Tristetraprolin (TTP), also known as zinc finger protein 36, is an RNA binding protein that has a significant role in regulating the expression of mRNAs containing AU-rich elements. We postulated that TTP might regulate interleukin (IL)-6 and IL-18 expression in diabetes. This study aimed to test the hypothesis that the levels of TTP are correlated with nephropathy in patients with type 2 diabetes. Methods Eighty-seven patients (61.3±9.6 years old) who had been diagnosed with type 2 diabetes mellitus and 41 age and sex matched healthy control subjects were enrolled. The diabetes patients were classified into those without proteinuria, with microalbuminuria, and with clinical proteinuria groups according to the ratio of urinary excretion of albumin/creatinine (ACR). Results Serum and urinary levels of IL-6 and IL-18 were significantly elevated, but those of TTP were significantly decreased in patients with diabetes as compared with control subjects. In addition, serum and urinary levels of IL-6 and IL-18 were significantly higher, but those of TTP were significantly lower in patients with proteinuria than in patients without proteinuria or with microalbuminuria. There was a significant correlation between serum TTP and IL-6/IL-18 (correlation coefficients of -0.572 and -0.685, P < 0.05). Conclusion These results show that diabetes with clinical proteinuria is accompanied by decreased urinary and serum level of TTP and increased levels of IL-6 and IL-18. Decreased TTP expression might occur prior to the increase in IL-6 and IL-18, and decrease of TTP might provide an earlier marker for glomerular dysfunction than IL-6 and IL-18.

The mechanism underlying epithelial‑to‑mesenchymal transition (EMT) caused by high glucose (HG) stimulation in diabetic nephropathy (DN) remains to be fully elucidated. The present study investigated the effects of HG on EMT and the activity of glycogen synthase kinase 3β (GSK‑3β) in podocytes and the kidneys of db/db mice, and assessed the effects of (2'Z, 3'E)‑6‑bromoindirubin‑3'‑oxime (BIO), an inhibitor of GSK‑3β, on EMT and glomerular injury. The resulting data showed that the activity of GSK‑3β was upregulated by HG and downregulated by BIO in the podocytes and the renal cortex. The expression levels of epithelial markers, including nephrin, podocin and synaptopodin, were decreased by HG and increased by BIO, whereas the reverse were true for mesenchymal markers, including α‑smooth muscle actin (α‑SMA) and fibronectin. The expression levels of β‑catenin and Snail, in contrast to current understanding of the Wnt signaling pathway, were increased by HG and decreased by BIO. In addition, expression of the vitamin D receptor (VDR) was decreased by HG and increased by BIO. In conclusion, the present study revealed that the mechanism by which BIO inhibited HG‑mediated EMT in podocytes and the renal cortex was primarily due to the VDR. Treatment with BIO protected renal function by maintaining the integrity of the filtration membrane and decreasing UAE, but not by regulating blood glucose. Therefore, GSK‑3β may be used as a sensitive biomarker of DN, and its inhibition by BIO may be effective in the treatment of DN.

The current study was to determine the predictors of survival in 491 Chinese patients with lupus nephritis (LN). All patients were evaluated and consecutively followed up from 2003 to 2010. The female: male ratio was 9.5:1, with a median age of 31.1 ± 12 years. Forty-nine (10.0%) patients were lost to follow-up and 47 (10.3%) patients died. The overall cumulative probability of survival at 5, 10, 15 and 20 years by Kaplan-Meier analysis was 88%, 77%, 53% and 45%, respectively. The log-rank test showed that the probability of survival was significantly decreased in the late-onset patients (≥50 years) ( P = 0.036), patients with hypoproteinaemia (≤35 g/l) ( P = 0.014), patients with increased creatinine (≥1.5 mg/dl) ( P = 0.002) and patients with massive proteinuria (≥3.5 g/24 h) ( P = 0.009). However, the probability of survival was significantly higher in patients treated with hydroxychloroquine (HCQ) ( P = 0.003) than those not treated with it. Based on a multivariate model, increased creatinine (hazard ratio (HR) = 2.041; P = 0.017) and proteinuria ≥3.5 g/24hours (HR=1.716; P = 0.016) were independent risk factors. Glucocorticoid (HR = 0.457; P = 0.01) and HCQ (HR=0.197; P = 0.026) were independent protective factors. Our findings suggest that renal dysfunction and massive proteinuria are independent risk factors for mortality. HCQ could improve the survival of patients with LN.