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.

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.

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.

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.

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.

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.

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.

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.

Astragalus mongholicus Bunge and Panax notoginseng (Burkill) F.H. Chen Formula for Renal Injury in Diabetic Nephropathy-In Vivo and In Vitro Evidence for Autophagy Regulation.

BACKGROUND: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus (DM) with limited treatment options. DN leads to progressive renal failure and accelerates rapidly into end-stage renal disease. Astragalus mongholicus Bunge and Panax notoginseng (Burkill) F.H. Chen formula (APF) is a traditional Chinese medicine (TCM) formula widely used to treat chronic kidney diseases (CKD) in the clinic in the southwest of China. The aim of this study is to explore how APF and its related TCM theory work on DN and whether mTOR/PINK1/Parkin signaling plays a part in this process. METHODS: HPLC was used for preliminary chemical analysis and quantitative analysis of the five components of APF. An in vivo autophagy deficiency model was established in C57BL/6 mice by streptozocin (STZ) combined with a high-fat and high-sugar diet, while the in vitro autophagy deficiency model was induced with high glucose (HG) in renal mesangial cells (RMCs). Renal histopathology staining was performed to investigate the extents of inflammation and injury. Real time-PCR and Western blotting techniques were utilized to assess autophagy-related proteins. RESULTS: APF significantly ameliorated renal injury in DN mice, specifically restoring blood urea nitrogen, serum creatinine, and 24-hour albuminuria. APF also reduced the mRNA and protein expressions of TNFα, IL-1ß, and IL-6 in STZ-induced DN mice. Furthermore, APF improved the autophagy deficiency induced by STZ in vivo or HG in vitro, as revealed by changes in the expressions of mTOR, PINK1, Parkin, Beclin 1, p62, and LC3B. Notably, inhibition of autophagy with 3-methyladenine in APF-treated RMCs aggravated cellular damage and altered mTOR/PINK1/Parkin signaling, indicating that APF rescued HG damage through promoting autophagy. CONCLUSION: APF may protect the kidneys from inflammation injuries in DN by upregulating autophagy via suppressing mTOR and activating PINK1/Parkin signaling. This experimental evidence strongly supports APF as a potential option for the prevention and treatment of DN.

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.

A meta-analysis of the effects of statin treatment on cardiovascular events and all-cause mortality in diabetic dialysis patients.

OBJECTIVES: Diabetic dialysis patients have higher risk of cardiovascular disease (CVD) than general population. While statin treatment is effective in prevention of CVD and all-cause mortality in general population, the use of statin in diabetic dialysis patients remains controversial. Thus, we aimed to assess the effects of statin treatment on prevention of CVD and all-cause mortality in diabetic dialysis patients by meta-analysis. MATERIALS AND METHODS: Pubmed, Embase and Cochrane Library were searched between each database's inception and July, 2014. Hazard ratio (HR) with 95% confidence interval (CI) for CVD and all-cause mortality was extracted from each study. The pooled analysis was performed using random-effects models by Stata 12.0. RESULTS: Our search yielded five eligible articles including two RCTs and three observational studies. By pooled estimate, statin treatment was associated with a decreased risk of the cardiac endpoint which included cardiac death and nonfatal MI (HR=0.84, 95% CI: 0.78-0.90) and all cardiac events combined (HR=0.89, 95% CI: 0.82-0.96). There was no difference in the overall incidence of fatal or nonfatal stroke (HR=1.24, 95% CI: 0.99-1.53) and all cerebrovascular events combined (HR=1.14, 95% CI: 0.98-1.33) between statin treatment and control group. Finally, statin treatment was associated with a decreased risk of all-cause mortality (HR=0.81, 95% CI: 0.71-0.92). CONCLUSIONS: Statin treatment may be beneficial for reducing the risk of cardiac events and all-cause mortality while have no effect on overall cerebrovascular events in diabetic dialysis patients. More RCTs were needed to validate the results.

[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.

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.

[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.

Ginsenoside-Rg1 protects podocytes from complement mediated injury.

AIM OF THE STUDY: Podocytes injury mediated by complement complex C5b-9 is the main feature of membranous nephropathy (MN). Little work has been done to prove that ginsenoside-Rg1 could inhibit this process. Our study aims to investigate the efficacy of ginsenoside-Rg1 in protecting the podocyte from complement mediated injury. MATERIALS AND METHODS: We chose sublethal C5b-9 induced podocyte injury as the model of MN in vitro. Ginsenoside-Rg1 was given as an intervention. Morphological changes were observed by electron microscope and fluorescence microscope. The production of reactive oxygen species (ROS) was detected by flow cytometry. The expression of the mitogen activated protein kinase (MAPK) including JNK, ERK and P38 was detected by western-blot technique. RESULTS: Ginsenoside-Rg1 could protect foot processes of podocytes, suppress the damage of F-actin, decrease the production of ROS, and inhibit the activation of P38 kinase pathway. CONCLUSION: These results suggest that ginsenoside-Rg1 could protect podocyte from sMAC-induced injury partly because of its antioxidant property and inhibit the activation of P38 kinase pathway.

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.