Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis.

BACKGROUND: Heart failure (HF) in patients undergoing maintenance hemodialysis (MHD) increases their hospitalization rates, mortality, and economic burden significantly. We aimed to develop and validate a predictive model utilizing contemporary deep phenotyping for individual risk assessment of all-cause mortality or HF hospitalization in patients on MHD. MATERIALS AND METHODS: A retrospective review was conducted from January 2017 to October 2022, including 348 patients receiving MHD from four centers. The variables were adjusted by Cox regression analysis, and the clinical prediction model was constructed and verified. RESULTS: The median follow-up durations were 14 months (interquartile range [IQR] 9-21) for the modeling set and 14 months (9-20) for the validation set. The composite outcome occurred in 72 (29.63%) of 243 patients in the modeling set and 39 (37.14%) of 105 patients in the validation set. The model predictors included age, albumin, history of cerebral hemorrhage, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/"sacubitril/valsartan", left ventricular ejection fraction, urea reduction ratio, N-terminal prohormone of brain natriuretic peptide, and right atrial size. The C-index was 0.834 (95% CI 0.784-0.883) for the modeling set and 0.853 (0.798, 0.908) for the validation set. The model exhibited excellent calibration across the complete risk profile, and the decision curve analysis (DCA) suggested its ability to maximize patient benefits. CONCLUSION: The developed prediction model offered an accurate and personalized assessment of HF hospitalization risk and all-cause mortality in patients with MHD. It can be employed to identify high-risk patients and guide treatment and follow-up.

Value of contrast-enhanced ultrasonography in radiofrequency ablation of secondary hyperparathyroidism.

OBJECTIVES: The purpose of the current study was to determine the performance of contrast-enhanced ultrasound (CEUS) in the assessment of radiofrequency ablation (RFA) of hyperplastic parathyroid glands due to secondary hyperparathyroidism (SHPT). METHODS: Thirty-two patients, each with ≥4 hyperplastic parathyroid glands due to SHPT, underwent RFA via hydro-dissection. CEUS was performed in each patient before and during RFA. The patients in whom the intact parathyroid hormone (iPTH) level did not decrease to 300 pg/ml were examined by CEUS. The iPTH, serum calcium, and serum phosphorus levels before and after RFA were compared. RESULTS: Ablation was achieved in all patients (131 ablated glands). The volume of the glands was 479.88 ± 549.3mm3. The pre-operative and day 1 post-operative iPTH levels were 2355 ± 1062 and 292.7 ± 306.8 pg/ml, respectively. Three nodules in three patients showed little enhancement on CEUS on post-operative day 1. The iPTH level was <300 pg/mL on post-operative day 1 in 23 patients, which indicated complete ablation; follow-up evaluations were therefore performed. The pre- and post-operative iPTH levels in the 23 patients were 2113 ± 787.2 and 106.2 ± 84.62 pg/ml, respectively (p < 0.05), and the 6- and 12-month post-operative iPTH levels were 111.1 ± 56.57 and 117.6 ± 97.08 pg/ml, respectively (p > 0.05). CONCLUSIONS: CEUS-guided RFA is effective and feasible for the treatment of ≥4 hyperplastic parathyroid glands. CEUS was shown to assist the surgeon before, during, and after RFA. CEUS on post-operative day 2, but not immediately post-operatively, was shown to accurately reflect gland perfusion.

Cyclosporine attenuates Paraquat-induced mitophagy and pulmonary fibrosis.

Objectives: Paraquat (PQ) poisoning can induce mitophagy and pulmonary fibrosis. Cyclosporine A (CsA) is an inhibitor of mitophagy. This study aimed at investigating whether CsA could inhibit PQ-induced mitophagy and pulmonary fibrosis in rats.Materials and Methods: Male Sprague-Dawley (SD) rats were treated with vehicle saline (control), 50 mg/kg PQ by gavage alone, or together with different doses of CsA. At 14 days post-induction, the levels of pulmonary fibrosis and PTEN-induced putative kinase 1 (PINK1) and Parkin expression in individual rats and mitochondrial membrane potential (MMP) in lung cells were measured. Moreover, A549 cells were treated with PQ or PQ + CsA for 24 h and the levels of PINK1, Parkin, fibronectin, collagen I and LC3 I and II expression and MMP were examined. Finally, the impact of PINK1 overexpression on the PQ or PQ + CsA-modulated fibronectin and collagen I expression in A549 cells was tested.Results: PQ exposure significantly increased the levels of hydroxyproline and collagen I expression and collagen fiber accumulation in the lung of rats, which were mitigated by CsA treatment. Furthermore, treatment with CsA significantly improved the PQ-decreased MMP and abrogated PQ-upregulated PINK1 and Parkin expression in the lungs of rats. In addition, CsA treatment decreased the PQ-induced fibrosis and mitophagy and PQ-impaired MMP as well as PQ-upregulated PINK1 and Parkin expression in A549 cells. The later effect of CsA was abrogated by PINK1 overexpression in A549 cells.Conclusions: Therefore, CsA can inhibit the PQ-induced mitophagy and pulmonary fibrosis by attenuating the PINK1/Parkin signaling.

[Investigation on the Influencing Factors of Adult Dyslipidemia in Shunqing District of Nanchong City].

OBJECTIVE: To analyze the risk factors of dyslipidemia of adult residents in Shunqing District of Nanchong City. METHODS: A five-stage stratified cluster sampling method was used to select adult residents from 9 communities in the urban area of Shunqing District of Nanchong City from January 2013 to April 2018 for questionnaires survey,physical measurement and laboratory test. Univariate analysis and multivariate logistic regression analysis were used to study the influencing factors of dyslipidemia. RESULTS: A total of 105 956 people was investigated,and the prevalence rate of dyslipidemia was 34.2% (36 272 cases). Among them, the prevalence rate of male was 38.11%, and 31.91% for female ( P<0.01). The proportion of dyslipidemia with hypertension, diabetes, and coronary heart disease was 13.46%, 5.74%, and 0.39%, respectively. The proportion of hypertension with diabetes was 2.79%. Multivariate logistic regression analysis showed that gender (odds ratio ( OR)=1.276, P<0.001), body mass index ( OR=1.052, P<0.001), education level (set ≤elementary school as reference, high school OR=1.094, P<0.001, ≥graduated OR=1.185, P<0.001), smoking history ( OR=1.124, P<0.001), coronary heart disease ( OR=1.189, P<0.001), hypertension ( OR=1.148, P<0.001),sdiabetes ( OR=1.967, P<0.001), and family history of dyslipidemia ( OR=1.760, P<0.001) were the influencing factors of dyslipidemia in residents of this region. Conclusions The dyslipidemia of urban residents in Nanchong area is highly concerned with hypertension, diabetes, and coronary heart disease. Male, obesity, high education level, smoking, coronary heart disease, hypertension, diabetes, and family history of dyslipidemia are risk factors for dyslipidemia in urban residents of Nanchong area. It is necessary to actively target the above risk factors and high-risk groups.

Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells.

Tubular epithelial-myofibroblast transition (TEMT) is an important process in renal tubulointerstitial fibrosis. Interleukin-1α (IL-1α) and transforming growth factor-ß1 (TGF-ß1) have been demonstrated to be key inducers of TEMT. In mouse embryonic fibroblast cells (NIH3T3), P311 protein induces phenotypic changes that are consistent to myofibroblast transformation. In the present study, we investigated the role of P311 gene and protein as well as potential mechanisms underlying TEMT in normal rat kidney tubular epithelial cells (NRK52E). Morphological and molecular changes were determined in NRK52E cells that were treated with IL-1α and/or P311 antibodies. The results showed that the NRK52E cells triggered by IL-1α became fibroblast-like cells, exhibiting hypertrophy of elongated and fusiform-shaped cells. IL-1α induced a time-dependent increase in P311 gene expression in NRK52E cells, with a peak time at 4 days. The expression levels of P311 gene were positively correlated with α-SMA and TGF-ß1 gene expression levels. Anti-P311 antibody inhibited P311 and α-SMA expression in the presence of IL-1α. In contrast, anti-P311 antibody increased the expression of TGF-ß1 gene in cells cultured with IL-1α. Therefore, P311 gene, together with α-SMA and TGF-ß1 genes, was induced in the process of TEMT. P311 protein triggered by interleukin-1α may promote TEMT through a TGF-ß1-independent pathway.

CagA, a major virulence factor of Helicobacter pylori, promotes the production and underglycosylation of IgA1 in DAKIKI cells.

While Helicobacter pylori (Hp) infection is closely associated with IgA nephropathy (IgAN), the underlying molecular mechanisms remain to be elucidated. This study was to investigate the effect of cytotoxin associated gene A protein (CagA), a major virulence factor of Hp, on the production and underglycosylation of IgA1 in the B cell line DAKIKI cells. Cells were cultured and treated with recombinant CagA protein. We found that CagA stimulated cell proliferation and the production of IgA1 in a dose-dependent and time-dependent manner. Moreover, CagA promoted the underglycosylation of IgA1, which at least partly attributed to the downregulation of ß1,3-galactosyltransferase (C1GALT1) and its chaperone Cosmc. In conclusion, we demonstrated that Hp infection, at least via CagA, may participate in the pathogenesis of IgAN by influencing the production and glycosylation of IgA1 in B cells.

[Causes of death in STZ-induced rat models of diabetes mellitus].

OBJECTIVE: To identify conditions that may improve the successful rate of STZ-induced rat models of diabetes mellitus (DM). METHODS: 100 male SD rats were randomly divided into control group (n = 10) and experimental group (n = 90). Rats in the experimental group were treated with intraperitoneal injection of STZ 65 mg/kg once, and were then categorized into succeeded DM model group and failed group. Their body masses and levels of fasting blood glucose (FBG), urine glucose (UG), urine protein (UP), urine routine, renal function, liver function, blood lipids and kidney hypertrophy index (KHI) were monitored and compared. Dead rats were dissected to observe diseased organs. Pathological changes of those diseased organs were examined by HE staining. RESULTS: DM rat models were established through a single intraperitoneal injection of STZ, with a success rate of 58.89%. During the experiment, 43.33% of rats died. Compared with the rats in the failed group, the DM rat models had significantly higher levels of body mass, food intake, water intake, urine output, FBG, creatinine, blood urea nitrogen, KHI, urinary tract infections, and mortality; but lower levels of total protein, albumin and cholesterol and triglyceride (P < 0.05). Nine rats died of pulmonary edema; 19 died of renal abscess. The causes of 11 dead rats were not clear. CONCLUSION: DM rat models can be established through a single intraperitoneal injection of STZ 65 mg/kg, but with high mortality rate. The deaths may be associated with infection, malnutrition, suffocation of lymphatic circulation, toxicity of STZ, and changes in environmental and climate conditions.

[Management of chronic kidney disease guided by the theory of Traditional Chinese Medicine: an experimental study].

OBJECTIVE: To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD). METHODS: A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison. RESULTS: Significant pre-intervention differences in age (P < 0.01), stage of glomerular filtration rate (GFR) (P = 0.007) and urine protein (P < 0.01) were found between the two groups of patients. But age, gender and proteinuria were not significant predictors on clinical outcomes of the patients in the multivariate regression models. The experimental group had a greater level of decrease in blood urea nitrogen (P < 0.01) and serum creatine (P < 0. 01) than the control group. No significant differences between the groups were found in changes of uric acid (P = 0.475), urine protein (P = 0.058), urine red cells (P = 0.577), and urine white cells (P = 0.01). A greater level of increase in estimated glomerular filtration rate was found in the experimental group compared with the control (P < 0.001). The multivariate linear regression analysis identified group (B = 0.395, P < 0.001) and stage of GFR (B = 0.165, P = 0.008) as significant predictors on the outcomes of treatment. CONCLUSION: The treatment of CKD patients guided by the theory of Traditional Chinese Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.

Noninvasive Evaluation of Lupus Nephritis Activity Using a Radiomics Machine Learning Model Based on Ultrasound.

Introduction: To explore whether ultrasonic radiomics extracted by machine learning method can noninvasively evaluate lupus nephritis (LN) activity. Materials and Methods: This retrospective study included 149 patients with LN diagnosed by renal biopsy. They were divided into a training cohort (n=104) and a test cohort (n=45). Ultrasonic radiomics features were extracted from the ultrasound images, and the radiomics features were constructed. Furthermore, five machine learning algorithms were compared to evaluate LN activity. The performance of the binary classification model was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: The average AUC of the five machine learning models was 79.4, of which the MLP model was the best. The AUC of the training group was 89.1, with an accuracy of 81.7%, a sensitivity of 83%, a specificity of 80.7%, a negative predictive value of 85.2%, and a positive predictive value of 78%. The AUC of the test group was 82.2, the accuracy was 73.3%, the sensitivity was 78.9%, the specificity was 69.2%, the negative predictive value was 81.8%, and the positive predictive value was 65.2%. Conclusion: Machine learning classifier based on ultrasonic radiomics has high accuracy for LN activity. The model can be used to noninvasively detect the activity of LN and can be an effective tool to assist the clinical decision-making process.

[Investigate the effects of compound radix notoginseng on renal interstitial fibrosis and kidney-targeting treatment].

OBJECTIVE: Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment. METHODS: 100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN) group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After operation, RN, CRN and ARB groups were intragastric administrated with RN (3 mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly included 18 rats for statistical analysis. The histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. Total kidney collagen content was determined by measuring the amount of hydroxyproline. The mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and quantified by real-time PCR. The expression of alpha-SMA protein was assessed by immunohistochemistry and Western blot analysis. RESULTS: In UUO model, the obstructed kidney showed typical features of renal tubulointerstitial fibrosis, such as severe tubular loss, dilation, atrophy, infiltration of inflammatory cells, interstitial matrix deposition (P < 0.05). Partial correlation assay showed that the expression of alpha-SMA was related to the renal tubular injury (r = 0.55; P < 0.05). Administration of RN, CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree. The expression of the alpha-SMA at mRNA and protein levels were significantly increased in the UUO group (P < 0.05), which was also suppressed by treatment with RN, CRN and ARB in different degree. Moreover, more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group. CONCLUSION: RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats, and CRN treatment is more effective than RN in reducing interstitial fibrosis.

Development and validation of a model to predict acute kidney injury following wasp stings: A multicentre study.

OBJECTIVE: To establish and validate a model to predict acute kidney injury (AKI) following wasp stings. METHODS: In this multicentre prospective study, 508 patients with wasp stings from July 2015 to December 2019 were randomly divided into a training set (n = 381) and a validation set (n = 127) for internal and external validation. Risk factors were identified, and a model was established to predict the probability of AKI following multiple wasp stings using an individual nomogram and a predictive formula. The performances of the model were assessed by using the area under the curve (AUC), accuracy (ACC) of the receiver operating characteristic curve and decision curve analysis. RESULTS: The number of stings, aspartate aminotransferase >147 U/L, lactate dehydrogenase >477 U/L, time from stings to admission >12 h and activated partial thromboplastin time >49 s were demonstrated to be independent risk factors for AKI following wasp stings (all P value < 0.05) and were incorporated into the model. The performances of the model were validated (AUC = 0.950 [95% CI: 0.923 to 0.969], ACC = 0.916 and AUC = 0.953 [95% CI: 0.900 to 0.982], ACC = 0.906 in the training set and validation set, respectively). The predictive formula and the nomogram of the model could be utilized to predict AKI following wasp stings, which have sufficient accuracies, good predictive capabilities and good net benefits. CONCLUSION: The predictive formula and the individual nomogram of the model might serve as promising predictive tools to assess the probability of AKI following wasp stings.

Contrast-associated acute kidney injury: An update of risk factors, risk factor scores, and preventive measures.

As lifespans lengthen, age-related diseases such as cardiovascular disease and diabetes are becoming more prevalent. Correspondingly, the use of contrast agents for medical imaging is also becoming more common, and there is increasing awareness of contrast-associated acute kidney injury (CA-AKI). There is no specific treatment for CA-AKI, and clinicians currently focus on prevention, interventions that alter its pathogenesis, and identification of risk factors. Although the incidence of CA-AKI is low in the general population, the risk of CA-AKI can reach 20% to 30% in patients with multiple risk factors. Many models have been applied in the clinic to assess the risk factors for CA-AKI, enable identification of high-risk groups, and improve clinical management. Hypotonic or isotonic contrast media are recommended to prevent CA-AKI in high-risk patients. Patients with risk factors should avoid using contrast media multiple times within a short period of time. All nephrotoxic drugs should be stopped at least 24 h before the administration of contrast media in high-risk populations, and adequate hydration is recommended for all patients. This review summarizes the pathophysiology of CA-AKI and the progress in diagnosis and differential diagnosis; updates the risk factors and risk factor scoring systems; reviews the latest advances related to prevention and treatment; discusses current problems in epidemiological studies; and highlights the importance of identifying high-risk subjects to control modifiable risk factors and use of a rating scale to estimate the risk and implement appropriate prevention strategies.

Potential role of imaging for assessing acute pancreatitis-induced acute kidney injury.

Acute kidney injury (AKI) is a common complication of acute pancreatitis (AP) that is associated with increased mortality. Conventional assessment of AKI is based on changes in serum creatinine concentration and urinary output. However, these examinations have limited accuracy and sensitivity for the diagnosis of early-stage AKI. This review summarizes current evidence on the use of advanced imaging approaches and artificial intelligence (AI) for the early prediction and diagnosis of AKI in patients with AP. CT scores, CT post-processing technology, Doppler ultrasound, and AI technology provide increasingly valuable information for the diagnosis of AP-induced AKI. Magnetic resonance imaging (MRI) also has potential for the evaluation of AP-induced AKI. For the accurate diagnosis of early-stage AP-induced AKI, more studies are needed that use these new techniques and that use AI in combination with advanced imaging technologies.

Prevalence and Risk Factors of Type 2 Diabetes and Prediabetes Among 53,288 Middle-Aged and Elderly Adults in China: A Cross-Sectional Study.

BACKGROUND: Diabetes is a metabolic disorder that causes a heavy burden on healthcare systems worldwide. The aim of this study was to determine the prevalence of type 2 diabetes and prediabetes and its associated factors among eight communities in Nanchong, China. METHODS: This was an observational cross-sectional study conducted throughout eight communities in Nanchong, China. The participants were 53,288 individuals aged 45 years or older. The participants' characteristics, comorbidities, health behaviors, family history, and dietary intake were assessed. Multinomial logistic regression models were fitted to identify factors associated with type 2 diabetes and prediabetes. RESULTS: The prevalence of diabetes and prediabetes was 13.9% (95% confidence interval [CI], 13.6-14.2) and 3.1% (95% CI, 2.9-3.2) of the population, respectively. After adjusting for other risk factors, advanced age, overweight, obesity, abdominal obesity, comorbidities, smoking, a family history of diabetes, and Chinese cooking vegetable intake were associated with an increased risk of type 2 diabetes and prediabetes. CONCLUSION: The prevalence of type 2 diabetes in the Chinese population is rising compared with data from the past. The risk factors of type 2 diabetes and prediabetes identified in this study will aid the identification of individuals at a high-risk of diabetes and the implementation of effective health promotion programs and campaigns. CLINICAL TRIAL REGISTRY NUMBER: ChiCTR-HOC-17013200.

Meta-Analytical Accuracy of ANCA Renal Risk Score for Prediction of Renal Outcome in Patients With ANCA-Associated Glomerulonephritis.

Background: To evaluate the diagnostic accuracy of antineutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for prediction of renal outcome in patients with ANCA-associated glomerulonephritis (ANCA-GN). Methods: We searched PubMed, EMBASE, Ovid, Web of Science, the Cochrane Library, and ClinicalTrials.gov for studies, which used ARRS to predict end-stage renal disease (ESRD) in patients with ANCA-GN. Two reviewers independently screened articles for inclusion, assessed the quality of studies with both an adapted Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. We calculated the combined patients with ESRD in the ARRS categories and presented the summary and individual estimates based on the ARRS categories. Then, the sensitivity, specificity, diagnostic odds ratio (DOR), positive/negative likelihood ratio, and the area under the receiver operating characteristic (AUROC) curves of the pooled data for ARRS were used to assess the accuracy of the "above the low-risk threshold" (ARRS ≥ 2) and "high-risk grade" (ARRS ≥ 8) for renal outcome of patients with ANCA-GN. The hierarchical summary ROC (HSROC) was used to verify the accuracy value. The clinical utility of ARRS was evaluated by the Fagan plot. Heterogeneity was explored using meta-regression and subgroup analysis. Results: A total of 12 distinct cohorts from 11 articles involving 1,568 patients with ANCA-GN were analyzed. The cumulative patients with ESRD at the maximum follow-up of 60 months was 5% (95% CI: 0.02-0.07; p < 0.001) for ANCA-GN with low ARRS (0-1 points) and significantly increased to 22% (95% CI: 0.15-0.29; p < 0.001) medium ARRS (2-7 points). The combined cumulative patients with ESRD was 59% (95% CI: 0.49-0.69; p < 0.001) high ARRS (8-11 points). The pooled sensitivity of ARRS ≥ 2 in predicting ESRD was 98% with a specificity of 30% and a DOR of 15.08 and the mean AUROC value was 0.82. The pooled sensitivity of ARRS ≥ 8 in predicting ESRD was 58% with a specificity of 86% and a DOR of 7.59. The meta-regression and subgroup analysis indicated that variation in the geographic regions, study design, index risk, follow-up time, age of patient, publication year, and number of patient could be the potential sources of heterogeneity in the diagnosis of ARRS ≥ 8. Conclusion: This meta-analysis emphasized the good performance of the ARRS score in predicting the renal outcome in patients with ANCA-GN. However, these findings should be verified by future large-scale prospective studies.

The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy.

PURPOSE: IgA1 aberrant O-glycosylation is one of the main pathogenetic features of IgA nephropathy (IgAN). This study attempted to determine the role of C1GALT1C1 in aberrant IgA1 O-glycosylation induced by lipopolysaccharide (LPS) and identify potential therapeutic targets in IgAN. METHODS: Lymphocytes isolated from 22 patients with IgAN and 17 normal controls were cultured for 3 to 7 days with or without LPS and 5-azacytidine (5-AZA). Expression levels of C1GALT1C1 mRNA and protein were measured by real-time PCR and Western blot analysis, respectively. Concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia villosa (VV) lectin-binding assay. Correlation analysis was performed between the expression of C1GALT1C1 protein and IgA1 O-glycosylation. RESULTS: Lymphocytes from patients with IgAN secreted more IgA1 than that from normal controls after LPS stimulation (P=0.26, 0.002 and 0.005 on the 3rd, 5th and 7th day, respectively) which could be inhibited by 5-AZA (P=0.001, 0.025 and 0.001 on the 3rd, 5th and 7th day, respectively). Moreover, LPS stimulation could obviously inhibit C1GALT1C1 expression in patients with IgAN (decreased by 71%, 82% and 92% on the 3rd, 5th and 7th day, respectively; P < 0.001), and cause a significant decrease of IgA1 O-glycosylation compared with normal controls (P=0.004, 0.003 and 0.03 on the 3rd, 5th and 7th day, respectively). When 5-AZA was added, the level of C1GALT1C1 expression increased dramatically (1.98, 5.53 and 8.97 times on the 3rd, 5th and 7th day, respectively; P < 0.001) along with an increase of IgA1 O-glycosylation (P=0.295, 0.09 and 0.003 on the 3rd, 5th and 7th day, respectively). However, normal controls showed no significant change in C1GALT1C1 expression and IgA1 O-glycosylation after LPS stimulation (P > 0.05). CONCLUSION: LPS induced IgA1 aberrant O-glycosylation and suppressed C1GALT1C1 expression in patients with IgAN. Upregulation of C1GALT1C1 expression by 5-AZA could reverse the IgA1 aberrant O-glycosylation. These results suggest that C1GALT1C1 may play a key role in the regulation of IgA1 O-glycosylation.

Ginsenoside Rg1 modulation on thrombospondin-1 and vascular endothelial growth factor expression in early renal fibrogenesis in unilateral obstruction.

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.

[Transforming growth TGF-beta1 mediates the expression of stromal cell derived factor-1 in kidney interstitial fibroblast cells in rats].

OBJECTIVE: To study the expression pattern of SDF-1 in the NRK49F cells and the role of TGF-beta1 in mediating the expression of SDF-1. METHODS: The SDF-1 mRNA and protein expression in the NRK49F cells with or without stimulating by TGF-beta1 was assayed with RT-PCR or Western blot or Immunohistochemistry. RESULTS: The SDF-1 mRNA expression stimulated by TGF-beta1 appeared in a time-dependent manner. The peak value appeared at 24 hours and was (2.924 +/- 0.235) times as high as the initial level. The dose-course studies suggested that TGF-beta1 stimulation resulted in marked promotion of SDF-1 mRNA expression, which peaked at the concentration of 5 ng/mL. At this concentration, the expression of SDF-1 mRNA was (2.113 +/- 0.314) times as high as that of the control. Corresponding with the pattern of mRNA expression of SDF-1, protein expression of SDF-1 was observed in NRK49F cells. A time-dependent manner was also observed in the protein expression of SDF-1 stimulated by 5 ng/mL of TGF-beta1. The protein expression of SDF-1 at 36 hours was (2.572 +/- 0.238) times as high as that of the control. TGF-beta1 neutralizing antibody reduced the expression of SDF-1 protein. CONCLUSION: SDF-1 expresses in NRK49F cells. TGF-beta1 up-regulates the mRNA and protein expressions of SDF-1 in NRK49F cells in a time- and concentration-dependent manner. As a chemokine, the increased expression of SDF-1 induced by TGF-beta1 may play an important role in renal inflammation and fibrosis.

[Effects of salidroside on tubular epithelial to myofibroblast transition under cobaltous chloride induced hypoxic status].

OBJECTIVE: To investigate the effect and possible mechanism of salidroside on the transdifferentiation of normal rat kidney tubular epithelia cells (NRK52E) under cobaltous chloride (Co) induced hypoxic status. METHODS: Cultured NRK52E cells were divided into control group, Co group and Co plus salidroside treatment groups at a dosage of 10 micromol/L, 50 micromol/L, and 100 micromol/L. Hypoxia-inducible factor-1alpha (HIF-1alpha), a master regulator of oxygen homeostasis was measured as a marker of hypoxic status. Morphologic alteration of cells was observed by inverted phase contrast microscope. The expression of alpha-SMA in NRK52E cells was detected by fluorescent immunocytochemistry (FICC) and immunohistochemistry (IHC). The alpha-SMA and TGF-beta1 mRNA were assessed using reverse transcription-polymerase chain reaction (RT-PCR). The expressions of HIF-1alpha and alpha-SMA protein were detected by Western blot analyses. The enzyme-linked immunosorbent assay was performed to detect collagen I (Col-I) and fibronectin (FN) in the supernatant. RESULTS: The expression of HIF-1alpha in NRK52E cells was induced by 100 micromol/L of Co in vitro. Co induced transdifferentiation of NRK52E cells, showing fibroblast-like in morphology. Salidroside partly blocked morphologic transformation of tubular epithelial cells. Salidroside decreased the expressions of alpha-SMA protein and mRNA and TGF-beta1 mRNA significantly (P < 0.05), although they were still higher than the controls (P <0 .05). Salidroside, especially in high dosage, inhibited the increase in Col-I and FN induced by Co (P < 0.05). CONCLUSION: Hypoxia can induce tubular epithelial-myofibroblast transdifferentiation (TEMT). Salidroside improves Co-induced hypoxic status and inhibits TEMT possibly through reducing Col I and FN in NRK52E cells.

[Leukemia inhibitory factor suppresses renal interstitial fibroblast activation induced by transforming growth factor].

OBJECTIVE: To investigate the effects of leukemia inhibitory factor (LIF) on renal interstitial fibroblast activation following induction by transforming growth factor beta 1 (TGF-beta1). METHODS: Normal rat interstitial fibroblast cells (NRK/49F) were treated with TGF-beta1 and TGF-beta1, combining with LIF respectively for different duration with different concentration. Changes in cell morphology and expression of alpha-SMA were evaluated with electronic microscope and Western blot respectively. The collagen I in the supernatant was detected with ABC-ELISA. RESULTS: TGF-beta1 induced renal interstitial fibroblast activation, and this was accompanied by significant morphological transformations and secretion of collagen I. Co-culturing of cells with LIF blocked the morphological transformation. In addition, LIF inhibited TGF-beta1-induced expression of alpha-SMA mRNA and protein (P < 0.01), and decreased the levels of collagen I (P < 0.01) in a dose-dependent manner. CONCLUSION: LIF suppresses TGF-beta1-induced activation and collagen I secretion of cultured renal interstitial fibroblasts.