Serum Sortilin Is Associated with Coronary Artery Calcification and Cardiovascular and Cerebrovascular Events in Maintenance Hemodialysis Patients.

OBJECTIVE: To analyze the role of serum sortilin in coronary artery calcification (CAC) and cardiovascular and cerebrovascular events (CCE) in maintenance hemodialysis (MHD) patients. METHODS: One hundred eleven patients with MHD ≥3 months were included in this study. The general data, clinical features, hematological data, and medication history of the patients were recorded. Eighty-five cases were examined by vascular color Doppler ultrasound, cardiac color Doppler ultrasound, lateral lumbar radiography, and coronary artery calcification score. The patients were followed up for a median time of 45 months. The primary endpoint was CCE or death from a vascular event, and the role of sortilin in this process was analyzed. RESULTS: Among 85 MHD patients, 51 cases (60.00%) had different degrees of CAC. There were significant differences in diabetes, dialysis time, serum phosphorus, calcium-phosphorus product, medical history of phosphate binders, sortilin, and carotid artery plaque between 4 different degrees of calcification groups (p < 0.05). Logistic regression analysis showed that diabetes (OR = 5.475; 95% CI: 1.794-16.71, p = 0.003), calcium-phosphorus product (OR = 2.953; 95% CI: 1.198-7.279, p = 0.019), and sortilin (OR = 1.475 per 100 pg/mL; 95% CI: 1.170-1.858, p = 0.001) were independent risk factors for CAC. During the follow-up, 28 cases of 111 patients (25.23%) suffered from CCE. There were significant differences in CCE between mild, moderate, and severe CAC groups and noncalcification groups (p < 0.05). Cox regression analysis showed that diabetes mellitus (HR 3.424; 95% CI: 1.348-8.701, p = 0.010), CAC (HR 5.210; 95% CI: 1.093-24.83, p = 0.038), and serum sortilin (HR = 8.588; 95% CI: 1.919-38.43, p = 0.005) were independent risk factors for CCE. Besides, we proposed a cutoff value of 418 pg/mL for serum sortilin level, which was able to predict the occurrence of CCE with 75.0% sensitivity and 71.9% specificity. The area under the curve was 0.778 (95% CI: 0.673-0.883). CONCLUSION: Sortilin is newly found to be independently associated with CAC and CCE in MHD patients.

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.

BACKGROUND: Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system. METHODS: We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2. RESULTS: Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression. CONCLUSION: This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

Efficacy and safety of Shenyankangfu Tablet, a Chinese patent medicine, for primary glomerulonephritis: A multicenter randomized controlled trial.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

Uric acid regulates NLRP3/IL-1ß signaling pathway and further induces vascular endothelial cells injury in early CKD through ROS activation and K+ efflux.

BACKGROUND: Chronic kidney disease (CKD) has been considered as a major health problem in the world. Increasing uric acid (UA) could induce vascular endothelial injury, which is closely related to microinflammation, oxidative stress, and disorders of lipids metabolism. However, the specific mechanism that UA induces vascular endothelial cells injury in early CKD remains unknown. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured and subjected to different concentrations of UA for different periods. Early CKD rat model with elevated serum UA was established. Western blotting and quantitative real-time PCR (qPCR) were applied for measuring protein and mRNA expression of different cytokines. The animals were sacrificed and blood samples were collected for measurement of creatinine, UA, IL-1ß, TNF-α, and ICAM-1. Renal tissues were pathologically examined by periodic acid-Schiff (PAS) or hematoxylin-eosin (HE) staining. RESULTS: The expression of IL-1ß, ICAM-1, NLRP3 complexes, and activation of NLRP3 inflammasome could be induced by UA, but the changes induced by UA were partially reversed by siRNA NLRP3 or caspase 1 inhibitor. Furthermore, we identified that UA regulated the activation of NLRP3 inflammasome by activating ROS and K+ efflux. In vivo results showed that UA caused the vascular endothelial injury by activating NLRP3/IL-1ß pathway. While allopurinol could reduce UA level and may have protective effects on cardiovascular system. CONCLUSIONS: UA could regulate NLRP3/IL-1ß signaling pathway through ROS activation and K+ efflux and further induce vascular endothelial cells injury in early stages of CKD.

Neferine inhibits LPS-ATP-induced endothelial cell pyroptosis via regulation of ROS/NLRP3/Caspase-1 signaling pathway.

BACKGROUND: Oxidative stress-induced endothelial dysfunction and pyroptosis play an important role during chronic kidney disease (CKD) progression. Neferine, which is an alkaloid ingredient from the lotus seed embryo, has many biological actions such as anti-inflammatory, anticancer and antioxidant. However, the role of neferine in endothelial cell pyroptosis and the involved mechanism remain obscure. The aim is to probe the protective effects of neferine on cell pyroptosis and the involved underlying mechanism. METHODS: After the HUVECs were primed with neferine treatment for 2 h prior to LPS and ATP exposure for 24 h, the cell proliferation was determined by BrdU; the cell LDH release was detected by LDH kits; the levels of intracellular ROS, MDA and SOD were tested by detection kits; Caspase-1 activity kit was used to determine caspase-1 activity; the contents of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and GSDMD were tested by RT-PCR and western blot. RESULTS: We found that neferine could inhibit LPS-ATP-induced oxidative stress and the activation of NLRP3 inflammasome signaling, and increased the endothelial cell viability and SOD production. siRNA which mediated the knockdown of NLRP3 promoted the neferine-induced inhibition effects of cell pyroptosis. Furthermore, these neferine-induced effects were reversed by the over-expression of NLRP3. CONCLUSIONS: Our findings indicated neferine may reduce ROS by anti-oxidation and inhibit LPS-ATP-induced endothelial cell pyroptosis via blocking ROS/NLRP3/Caspase-1 signaling pathway, which provides the evidence for therapeutic effect in CKD.

Acute Peritoneal Dialysis System for Neonates with Acute Kidney Injury Requiring Renal Replacement Therapy: A Case Series.

BACKGROUND: Acute kidney injury (AKI) is common in critically ill neonates, and peritoneal dialysis (PD) can be a lifesaving option. In China, however, much of the equipment for PD in neonates is not available. We describe results with a novel system for PD, which has been developed locally to improve access to therapy and care for critically ill neonates requiring PD in China. METHODS: The system comprises a 14-gauge single-lumen central venous catheter serving as a PD catheter, inserted by Seldinger technique, with an adapted twin bag PD system. Ten neonates with AKI were treated using the novel PD system. RESULTS: The 10 patients ranged in age from 1 day to 22 days, with bodyweights between 700 g and 3,300 g. Average time to renal function recovery was between 14 and 96 hours. Complications related to the novel PD system included leak (n = 1), catheter displacement (n = 1), and catheter obstruction (n = 1). There were no complications related to insertion, no cases of peritonitis or exit-site infection, and no subsequent hernias. A comparison of costs indicated that the novel PD system is less expensive than conventional systems involving open insertion of Tenckhoff catheters. CONCLUSIONS: Peritoneal dialysis using the novel PD system is simple, safe, and effective for suitable neonates with AKI in China.

Prevalence and risk factors for vascular calcification in Chinese patients receiving dialysis: baseline results from a prospective cohort study.

OBJECTIVE: With limited data available on calcification prevalence in chronic kidney disease (CKD) patients on dialysis, the China Dialysis Calcification Study (CDCS) determined the prevalence of vascular/valvular calcification (VC) and association of risk factors in Chinese patients with prevalent hemodialysis (HD) or peritoneal dialysis (PD). METHODS: CKD patients undergoing HD/PD for ≥6 months were enrolled. Prevalence data for calcification and medical history were documented at baseline. Coronary artery calcification (CAC) was assessed by electron beam or multi-slice computed tomography (EBCT/MSCT), abdominal aortic calcification (AAC) by lateral lumbar radiography, and cardiac valvular calcification (ValvC) by echocardiography. Serum phosphorus, calcium, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D and FGF-23 were evaluated. A logistic regression model was used to evaluate the association between risk factors and VC. RESULTS: Of 1,497 patients, 1,493 (78.3% HD, 21.7% PD) had ≥1 baseline calcification image (final analysis cohort, FAC) and 1,423 (78.8% HD, 21.2% PD) had baseline calcification data complete (BCDC). Prevalence of VC was 77.4% in FAC (80.8% HD, 65.1% PD, p < .001) and 77.5% in BCDC (80.7% HD, 65.8% PD). The proportion of BCDC patients with single-site calcification were 20% for CAC, 4.3% for AAC, and 4.3% for cardiac valvular calcification (ValvC), respectively. Double site calcifications were 23.4% for CAC and AAC, 6.5% for CAC and ValvC, and 1.1% for AAC and ValvC, respectively. In total, 17.9% patients had calcification at all three sites. CONCLUSIONS: High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.

SB-216763, a GSK-3ß inhibitor, protects against aldosterone-induced cardiac, and renal injury by activating autophagy.

Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays a pivotal role in the pathogenesis of hypertension and renal fibrosis. GSK-3ß contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced hypertension, and renal damage is not clear. In the present study, rats were treated with Aldo combined with SB-216763 (a GSK-3ß inhibitor) for 4 weeks. Hemodynamic, cardiac, and renal parameters were assayed at the indicated time. Here we found that rats treated with Aldo presented cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of molecular markers attesting inflammation and fibrosis were increased by Aldo infusion, whereas the treatment of SB-216763 reversed these alterations. SB-216763 suppressed cardiac and renal inflammatory cytokines levels (TNF-a, IL-1ß, and MCP-1). Meanwhile, SB-216763 increased the protein levels of LC3-II in the cardiorenal tissues as well as p62 degradation, indicating that SB-216763 induced autophagy activation in cardiac, and renal tissues. Importantly, inhibition of autophagy by 3-MA attenuated the role of SB-216763 in inhibiting perivascular fibrosis, and tubulointerstitial injury. These data suggest that SB-216763 protected against Aldo-induced cardiac and renal injury by activating autophagy, and might be a therapeutic option for salt-sensitive hypertension and renal fibrosis.

[Values of combination of urinary L-FABP and NGAL in early diagnosis of acute kidney injury after cardiac surgery in children].

OBJECTIVE: To investigate the values of combination of urinary liver-type fatty acid-binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) in early diagnosis of acute kidney injury (AKI) after cardiac surgery in children. METHODS: A total of 97 children with congenital heart disease undergoing cardiopulmonary bypass surgery were enrolled. Serum and urine samples were collected before and after surgery. Levels of serum creatinine (Scr), urinary L-FABP, and urinary NGAL from AKI group (n=18) and non-AKI group (n=79) were measured, and the postoperative dynamic changes in these markers were compared between the two groups. The receiver operating characteristic (ROC) curve and the area under ROC curve (AUC) were used to assess the values of these markers alone or in combination in the prediction of postoperative AKI. RESULTS: The levels of urinary L-FABP and NGAL in the AKI group were significantly higher than those in the non-AKI group at 2 and 6 hours after surgery, and the changes in their concentrations were earlier than Scr. The AUCs of urinary L-FABP alone in predicting AKI at 2 and 6 hours after surgery were 0.921 and 0.896 respectively, and those of urinary NGAL alone were 0.908 and 0.928 respectively. Those of their combination were 0.942 and 0.929 respectively. CONCLUSIONS: Urinary L-FABP and NGAL significantly increase in the early stage of AKI after cardiac surgery in children, which are significantly earlier than the changes in Scr. They can be used to predict the occurrence of AKI in the early stage. A combination of the two biomarkers can further improve the accuracy of diagnosis.

Low Ratio of Treg to Th17 Cells After 36 Weeks of Telbivudine Therapy Predict HBeAg Seroconversion.

Changes of Treg/Th17 cells ratio and their associated cytokines have some correlations with an immune modulatory effect of Telbivudine treatment. The aim of our study was to investigate the role of the dynamic ratio of Treg/Th17 cells in the mechanism of LdT therapy and their relationships with the clinical responses. We detected the frequency and cytokines production of Treg and Th17 cells in 28 hepatitis B envelope antigen (HBeAg)-positive CHB patients at 0, 12, 24, 36, 48, and 96 weeks after initial LdT therapy. LdT could upregulate the frequency of Th17 cells and Th17 cells associated cytokines, downregulated the frequency of Treg cells and level of TGF-ß, which leads to the decrease of Treg/Th17 ratio in HBeAg-positive CHB patients. Treg/Th17 ratio at treatment week 36 could independently predict HBeAg seroconversion in the first 2 years of Telbivudine treatment. Telbivudine therapy can decrease Treg/Th17 ratio, which may predict HBeAg seroconversion during treatment.

[Clinical observation on two-way quintuple puncture in the treatment of ganglion].

OBJECTIVE: To explore the better therapy in the treatment of ganglion. METHODS: Ninety cases of ganglion were randomized into a two-way quintuple puncture group, a common quintuple puncture group and a fire needling group, 30 cases in each one. In the two-way quintuple puncture group, the "9-in-1" multiple penetrating needling technique was used. In the common quintuple puncture group, the traditional "5-in-1" multiple penetrating needling technique was applied. In the fire needling group, the traditional multiple fire needling technique was adopted. The treatment was given once a day, 3 treatments made one session and the efficacy was analyzed statistically after 1 session treatment in the three groups. RESULTS: All of the three therapeutic methods achieved the efficacy on ganglion. The curative rate was 96. 7% (29/30) in the two-way quintuple puncture group, which was better obviously than 66.7% (20/30) in the common quintuple puncture group and 60. 0% (18/30) in the fire needling group (both P<0. 01). CONCLUSION: The two-way quintuple puncture technique achieves the remarkably superior efficacy on ganglion as compared with the common quintuple puncture technique and fire needling technique.

The effects of combined treatment with sevoflurane and cisplatin on growth and invasion of human adenocarcinoma cell line A549.

Sevoflurane, an inhalational anesthetic, and cisplatin (DDP)-based chemotherapy have been widely used during lung cancer surgery. However, the effect of sevoflurane on the sensitivity of lung cancer cells to DDP chemotherapy remains unclear. In this study, the effects of combined treatment with sevoflurane and cisplatin on the growth and invasion of human lung adenocarcinoma A549 cell line have been investigated. The underlying mechanism has also been explored. In our experiment, A549 cells were treated with 2.5% sevoflurane, 10µmol/L DDP, or the co-treatment of sevoflurane and DDP for 4h, respectively. Cell proliferation was evaluated by the MTT assay and colony formation assay. Apoptosis was assessed by flow cytometry. Cell invasion was detected by Transwell assay. The expressions of X-linked inhibitor of apoptosis protein (XIAP), Survivin, matrix metalloproteinase (MMP)-2 and MMP-9 were determined by western blotting. Our results showed that sevoflurane combined with DDP resulted in a more pronounced inhibition of tumor cells growth and invasion as compared with either drug alone. Besides, XIAP, Survivin, MMP-2, and MMP-9 were downregulated more significantly by the co-treatment of the two drugs as compared to sevoflurane treatment or DDP treatment alone. Taken together, the growth-inhibitory and invasion-inhibitory synergy between sevoflurane and DDP in human adenocarcinoma A549 cell line was found in this study. Furthermore, we showed that the growth-inhibitory synergy between sevoflurane and DDP might be associated with the downregulation of XIAP and Survivin, and the invasion-inhibitory synergy between sevoflurane and DDP might be involved in the downregulation of MMP-2 and MMP-9.

WITHDRAWN: Propofol reduces MMPs expression by inhibiting PI3K/AKT activity in human HepG2 cells.

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Biological characteristics of the rtA181T/sW172* mutant strain of Hepatitis B virus in animal model.

BACKGROUND: The effects of Hepatitis B virus (HBV) rtA181T/sW172* mutation on viral replication and pathogenicity was concerned recently. This study aimed to investigate the biological characteristics of rtA181T/sW172* mutant strain of HBV in animal model. METHODS: The rtA181T/sW172* mutant plasmid was constructed using the pHBV4.1 (wild type HBV) as a template. The wild and mutant HBV replication mouse models were established utilizing a hydrodynamic technique. The titers of hepatitis B surface antigen (HBsAg), hepatitis B e antigen, and HBV DNA in serum, and the levels of HBsAg, hepatitis B core antigen(HBcAg), HBV DNA replication intermediates (HBV DNA RI) and HBV RNA in liver were measured after 1, 3, 5, 7, 10, 12 and 15 days of plasmid injection. RESULTS: In wild-type HBV replication mouse model, serum HBsAg was high on day 1, 3, and 5, but became lower since day 7; while in mutant HBV mouse model, serum HBsAg was always at very low level. In liver tissues, HBV DNA RI of wild type HBV was detected on day 1 after transfection. The level subsequently peaked on day 3, gradually declined after day 5, and was almost undetectable on day 10. However, the HBV DNA RI levels of the mutant strain were always higher and lasted longer until day 15. Consistently, the expression levels of HBsAg and HBcAg in liver of the mutant group were significantly increased. CONCLUSIONS: In the case of the HBV rtA181T/sW172* mutation, the secretion of serum HBsAg was impaired, whereas HBV DNA replication and HBsAg/HBcAg expression were increased in liver. These results suggest that the mutation can impair HBsAg secretion, and may cause the accumulation of viral core particles in liver.

[Effects of Chinese herbal medicine Neiyi Recipe-medicated serum on angiopoiesis of endometriosis in the chick chorioallantoic membrane model].

OBJECTIVE: To compare angiopoiesis ability of eutopic and ectopic endometrial tissue isolated from women with endometriosis and endometrium isolated from women without endometriosis (control), and to explore the inhibitory effects of medicated serum of Neiyi Recipe, a compound traditional Chinese herbal medicine. METHODS: Chick chorioallantoic membrane (CAM) model of endometriosis was established by transplanting endometrium onto CAM. The CAMs were then hatched with blank serum or medicated serum of danazol or Neiyi Recipe, which were prepared in rats by orally administering. The sizes of the transplanted tissue and new vessels around the transplanted tissue were measured. Expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemical method. RESULTS: There was no difference in the sizes of transplanted tissue among CAM models of ectopic and eutopic endometrial tissue isolated from women with endometriosis or control (P>0.05), and more new vessels were found around the ectopic and eutopic endometrial tissue than the endometrial tissue of control (P<0.05). Compared with the controls, the size of the transplanted tissue and positive area of new vessels were significantly inhibited by Neiyi Recipe-medicated serum (P<0.01, P<0.05), and similar changes happened in the danazol groups, except for the size of transplanted tissue from ectopic endometrial tissue (P>0.05). Expression of VEGF was significantly higher in eutopic and ectopic endometrial tissue than in the control (P<0.01); the level of VEGF obviously reduced in the Neiyi Recipe and danazol groups (P<0.01), but no significant difference was detected between them. CONCLUSION: Endometrium from women with endometriosis stimulates the formation of new vessels by increase the expression of VEGF. Neiyi Recipe-medicated serum significantly decreases the expression of VEGF in eutopic and ectopic endometrial tissues and thus restrains the formation of new vessels, reduces the blood supply and inhibits growth of ectopic endometrial tissue, which are similar to danazol, but has greater efficacy in suppressing the expression of VEGF.

Fibroblast growth factor-23 and interleukin-6 are risk factors for left ventricular hypertrophy in peritoneal dialysis patients.

BACKGROUND: Left ventricular hypertrophy (LVH) is a major risk factor for cardiovascular death in dialysis patients. Fibroblast growth factor-23 (FGF-23) and interleukin-6 (IL-6) were thought to be related to cardiovascular diseases (CVDs) in dialysis. METHODS: To determine the relationship between FGF-23, IL-6 and LVH in continuous ambulatory peritoneal dialysis (CAPD) patients, serum FGF-23 and IL-6 levels as well as standard laboratory parameters were assessed in 62 CAPD patients and 30 healthy controls. LVH was determined by echocardiography in dialysis patients. RESULTS: Serum FGF-23 and IL-6 levels were significantly higher in CAPD patients than in healthy controls, whereas both were higher in patients with LVH than in patients without LVH. FGF-23 was found to be positively associated with left ventricle mass index (LVMI) and serum phosphate. IL-6 level was positively associated with LVMI and negatively correlated with serum albumin and hemoglobin. Serum FGF-23 level was positively correlated with IL-6 level. CONCLUSION: FGF-23 and IL-6 are independent risk factors for LVH in CAPD patients and both collaborated in causing LVH in CAPD.

Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis.

INTRODUCTION: Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily that functions through binding to Fn14 receptor in target cells. TWEAK has multiple biological activities. Studies show that TWEAK plays an important role in immune inflammatory diseases. Recent work has revealed that TWEAK may play an important role in the pathogenesis of kidney damage, including in systemic lupus erythematosus (SLE), where its concentration in urine was correlated with the level of activity of lupus nephritis (LN). OBJECTIVE: The major focus of this review is to discuss the recent studies on TWEAK and its possible role in the pathogenesis of LN, and the therapeutic potential of modulating this pathway in LN. RESULTS AND CONCLUSION: TWEAK plays a key role in the pathogenesis of LN through activation of multiple down-signaling pathway, inducing proinflammatory cytokines and chemokines, affecting cell proliferation/apoptosis and inducing renal IgG deposition. TWEAK blockade may be a novel therapeutic approach to reducing renal damage in SLE.

Functional Characterization of Interferon Regulation Element of Hepatitis B virus Genome In Vivo.

The roles of interferon regulatory element (IRE) in Hepatitis B virus (HBV) genome on inhibitory effect of interferon against HBV are controversial in vitro. This study aimed to determine the functional characterization of HBV-IRE sequence in vivo. Wild-type or IRE-mutant HBV replication-competent mice were firstly established, and mice were subquently treated with polyinosinic-polytidylin acid (polyI.C) or phosphate-buffered saline via intraperitoneal. Results showed that PolyI.C inhibited viral replication, and increased the level of 2',5'-oligoadenylate synthase mRNA transcripts, a marker of INF-α/ß induction. Between wild-type and IRE-mutant HBV replication-competent mice, the levels of HBV-RNA and HBV-DNA replication intermediates were similar. After PolyI.C treatment, the decreasing of HBV-RNA was similar between two groups, but HBV-DNA replication intermediates decreased significantly less in IRE-mutant than wild-type HBV replication-competent mice. These findings suggested that IRE mutant reduced the inhibitory effect of interferon on HBV replication, which played a role in antiviral effect of interferon against HBV.

[Adhesive and invasive effects and mechanism of neiyi recipe on the endometriosis].

OBJECTIVE: To assess the inhibitory effects of Neiyi Recipe by comparing adhesive and invasive effects of eutopic and ectopic endometrial tissues from endometriosis women and the endometrium from endometriosis-free women. METHODS: The invasive capacity of endometrial stromal cells from endometriosis-free women, eutopic and ectopic endometrial stromal cells from women with endometriosis were compared using Boyden chamber, the chick chorioallantoic membrane (CAM) ectopy transplant, and immunohistochemical EnVision method. The expressions of adhesion and invasion correlated cytokines in the transplanted tissue and effect of Neiyi Recipe on them were observed. RESULTS: The numbers of invasion stromal cells of eutopic and ectopic endometrial tissues were obviously more than those in the endometriosis-free women (P<0.05). After treatment with Neiyi Recipe and danazol respectively, the number of invasion stromal cells was significantly less in the Neiyi Recipe group than in the danazol group (P<0.05). Compared with endometriosis-free women, the expression of ICAM-1 in the ectopic endometrium tissue, and MMP-9 expressions in the eutopic and ectopic endometrium were significantly higher (all P<0.05) and TIMP-1 expressions obviously lower (P<0.01). In the eutopic endometrium, Neiyi Recipe and danazol serum could significantly lower the expression of MMP-9, and up-regulate expressions of TIMP-1 and ICAM-1 (P<0.01). In the ectopic endometrium, Neiyi Recipe could significantly lower the expression of MMP-9 (P<0.01) and ICAM-1 (P<0.05), and danazol serum could lower the expression of ICAM-1 (P<0.05). Compared with danazol, Neiyi Recipe showed more obvious effect in down-regulating MMP-9 (P<0.05). CONCLUSIONS: High expression of MMP-9 and low expression of TIMP-1 existed in eutopic and ectopic endometrial tissues of endometriosis, which could enhance the ectopic invasion and transplant of endometrial cells. Neiyi Recipe could inhibit the invasion of endometrial stromal cells and the expression of MMP-9.

Fosinopril and losartan regulate klotho gene and nicotinamide adenine dinucleotide phosphate oxidase expression in kidneys of spontaneously hypertensive rats.

BACKGROUND/AIMS: Klotho, a newly identified antiaging gene, predominantly detected in the kidney, has pleiotropic protective effects on kidney diseases. Several studies have confirmed the association between Klotho and oxidative stress. The present studies were performed to explore effects of fosinopril (Fos) and losartan (Los) on Klotho and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression in kidneys of spontaneously hypertensive rats (SHR). METHODS: Twenty-four male 22-week-old SHR were randomly divided into three groups: model group, Fos group and Los group. Wistar-Kyoto rats were taken as control. After 8 weeks, urinary N-acetyl-ß-D-glucosaminidase (NAGase), 24 h urinary protein (Upro), serum creatinine (Scr), blood urea nitrogen (BUN) and renal pathological changes were detected. Renal mRNA and protein expression of Klotho and three subunits of NADPH oxidase protein expression were evaluated. RESULTS: As compared to the model group, NAGase, Upro, Scr and BUN were decreased; the typical renal pathological damage was relieved in the Fos or Los group. Fos or Los inhibited the reduction of Klotho expression, and reduced the elevation of NADPH oxidase expression. CONCLUSION: Abnormal expression of Klotho and NADPH oxidase plays important roles in progression of hypertensive renal damage. Fos and Los can increase Klotho expression, and inhibit NADPH oxidase expression, which may be one of the mechanisms of their protective effects in hypertensive renal damage.