Inhibitory Effect of PPARδ Agonist GW501516 on Proliferation of Hypoxia-induced Pulmonary Arterial Smooth Muscle Cells by Regulating the mTOR Pathway.

OBJECTIVE: This study aimed to investigate the effects of the peroxisome proliferator-activated receptor δ (PPARδ) agonist GW501516 on the proliferation of pulmonary artery smooth muscle cells (PASMCs) induced by hypoxia, in order to search for new drugs for the treatment and prevention of pulmonary vascular remodeling. METHODS: PASMCs were incubated with different concentrations of GW501516 (10, 30, 100 nmol/L) under the hypoxic condition. The proliferation was determined by a CCK-8 assay. The cell cycle progression was analyzed by flow cytometry. The expression of PPARδ, S phase kinase-associated protein 2 (Skp2), and cell cycle-dependent kinase inhibitor p27 was detected by Western blotting. Then PASMCs were treated with 100 nmol/ L GW501516, 100 nmol/L mammalian target of rapamycin (mTOR) inhibitor rapamycin and/or 2 µmol/L mTOR activator MHY1485 to explore the molecular mechanisms by which GW501516 reduces the proliferation of PASMCs. RESULTS: The presented data demonstrated that hypoxia reduced the expression of PPARδ in an oxygen concentration- and time-dependent manner, and GW501516 decreased the proliferation of PASMCs induced by hypoxia by blocking the progression through the G0/G1 to S phase of the cell cycle. In accordance with these findings, GW501516 downregulated Skp2 and upregulated p27 in hypoxia-exposed PASMCs. Further experiments showed that rapamycin had similar effects as GW501516 in inhibiting cell proliferation, arresting the cell cycle, regulating the expression of Skp2 and p27, and inactivating mTOR in hypoxia-exposed PASMCs. Moreover, MHY1485 reversed all the beneficial effects of GW501516 on hypoxia-stimulated PASMCs. CONCLUSION: GW501516 inhibited the proliferation of PASMCs induced by hypoxia through blocking the mTOR/Skp2/p27 signaling pathway.

[Effects of GW501516 on the proliferation of pulmonary artery smooth muscle cells induced by hypoxia and its mechanisms].

Objective: To investigate the effects of the peroxisome proliferator-activated receptor δ (PPARδ) agonist GW501516 on the proliferation of primary rat proliferation of pulmonary artery smooth muscle cells ( PASMCs ) induced by hypoxia, in order to discover new drugs for the treatment and prevention of pulmonary vascular remodeling. Methods: The PASMCs in the control group were cultured with 21% oxygen, while the PASMCs in the hypoxia group were cultured with 3% oxygen to induce cell proliferation. PASMCs were incubated with GW501516 at the concentrations of 10, 30 and 100 nmol/L under hypoxic conditions for different time points (12, 24, and 48 h) to find out the appropriate concentrations of GW501516 for inhibition the proliferation. PASMCs were incubated with 100 nmol/L GW501516 and ( or ) protein kinase B (AKT) agonist SC79 for 24 h to explore related mechanisms of GW501516 in regulating the proliferation. The proliferation and DNA synthesis were determined by CCK-8 and BrdU kit. The cell cycle progression was analyzed by flow cytometry. The mRNA expressions of Cyclin D1 and the cyclin kinase inhibitor p27(p27) were measured by quantitative real-time PCR (RT-PCR). The expressions of PPARδ, total and phosphorylated forms AKT and glycogen synthase kinase 3ß (GSK3ß) were detected by Western blot. Results: Compared with the hypoxia group, PASMCs incubated with different concentrations of GW501516 (10, 30, 100 nmol/L) for 12, 24, 48 h under hypoxic conditions could inhibit the proliferation and DNA synthesis, and the greatest level of suppression of proliferation was induced by GW501516 at the concentration of 100 nmol/L(P＜0.05 or P＜0.01). Compared with the control group, the expression of PPARδ was upregulated markedly in PASMCs incubated with 100 nmol/L GW501516 for 24 h,while hypoxia could downregulate the expression of PPARδ significantly(P＜0.01). Compared with the hypoxia group, 100 nmol/L GW501516 blocked the proliferation and DNA synthesis of PASMCs significantly(P＜0.01), increased the proportion of PASMCs in G0 /G1 phase while decreased the proportion of PASMCs in S phase and G2 /M phase(P＜0.05 or P＜0.01), markedly downregulated the mRNA expression of cyclin D1 and upregulated the mRNA expression of p27(P＜0.01), significantly inhibited the protein expressions of phosphorylated AKT and GSK3ß(P＜0.01). Compared with the 100 nmol/L GW501516 hypoxia group, AKT agonist SC79 reversed all the above effects of 100 nmol/L GW501516 on hypoxia stimulated PASMCs(P＜0.05 or P＜0.01). Conclusion: GW501516 inhibits hypoxia induced proliferation in PASMCs via inactivating AKT/GSK3ß signaling pathway.

Abnormal glucose regulation in Chinese patients with coronary artery disease: a gender analysis.

BACKGROUND: Diabetes and impaired glucose regulation are very common in patients with coronary artery disease (CAD). In this study, we aim to investigate the prevalence of abnormal glucose regulation in men and women in Chinese CAD patients. METHODS: In this retrospective study, 4100 patients (male, n = 2873; female, n = 1227)with CAD were enrolled. The mean age of these patients was 63 years. The demographic data, medical history, echocardiography findings and blood investigations were collected and analyzed. RESULTS: In this population, 953 (24%) patients had definite diagnosis of type 2 diabetes mellitus, including 636 males (23%) and 317 females (27%). There was a higher prevalence of diabetes in females than men (p < 0.05). For the remaining patients, 48% (n = 959) undergone an oral glucose tolerance test (OGTT), which revealed that 83 male patients (12%) and 41 female patients (16%) suffered from the type 2 diabetes (p > 0.05). 283 men (40%) and 105 women (41%) had impaired glucose regulation (IGR) (p > 0.05). Only 338 men (25%) and 109 women (19%) showed the normal glucose regulation, implying a higher prevalence of abnormal glucose regulation in females (p < 0.01). The odd ratio (OR) showed that women were more prone to have diabetes mellitus or IGT than men and the OR was 1.44 and 1.43 respectively. CONCLUSION: Abnormal glucose regulation is highly prevalent in CAD patients. The women are more prone to have diabetes mellitus or IGT than men.

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.

Ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries: a systematic review.

PURPOSE: We performed a systematic review of the ethical, social, and cultural issues associated with delivery of genetic services in low- and middle-income countries (LMICs). METHODS: We searched 11 databases for studies addressing ethical, social, and/or cultural issues associated with clinical genetic testing and/or counselling performed in LMICs. Narrative synthesis was employed to analyze findings, and resultant themes were mapped onto the social ecological model (PROSPERO #CRD42016042894). RESULTS: After reviewing 13,308 articles, 192 met inclusion criteria. Nine themes emerged: (1) genetic counseling has a tendency of being directive, (2) genetic services have psychosocial consequences that require improved support, (3) medical genetics training is inadequate, (4) genetic services are difficult to access, (5) social determinants affect uptake and understanding of genetic services, (6) social stigma is often associated with genetic disease, (7) family values are at risk of disruption by genetic services, (8) religious principles pose barriers to acceptability and utilization of genetic services, and (9) cultural beliefs and practices influence uptake of information and understanding of genetic disease. CONCLUSION: We identified a number of complex and interrelated ethical, cultural, and social issues with implications implications for further development of genetic services in LMICs.

Author Correction: Accelerating polygon beam with peculiar features.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

[Two new polypeptides from extract of deer bone extract].

Two new polypeptides were isolated and purified from the extract of deer bone (constitutive part of Cucumis and Cervus polypeptide injection) by various column chromatography including C4 300Å and Sephadex G-50, as well as semipreparative HPLC. Their N-terminal amino acid sequences were identified by De Novo sequencing on the basis of MALDI-TOF-MS data and Explorer™ software. The N-terminal amino acid sequences of polypeptides were identified as NH2-Gly-Pro-Val-Gly-Pro-Thr-Gly-Pro-Val-Gly-Ala-Ala-Gly-Pro-Ser-Gly-Pro-Asp (Mei18 peptide, 1) and NH2-Ala-Gly-Pro-Ala-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Pro-Asp-Ser-Try-Asp (Mei23 peptide, 2), respectively. Mei18 and Mei 23 peptides are new polypeptides.

Accelerating polygon beam with peculiar features.

We report on a novel kind of accelerating beams that follow parabolic paths in free space. In fact, this accelerating peculiar polygon beam (APPB) is induced by the spectral phase symmetrization of the regular polygon beam (RPB) with five intensity beam (RPB) with five intensity peaks, and it preserves a peculiar symmetric structure during propagation. Specially, such beam not only exhibits autofocusing property, but also possesses two types of accelerating intensity maxima, i.e., the cusp and spot-point structure, which does not exist in the previously reported accelerating beams. We also provide a detailed insight into the theoretical origin and characteristics of this spatially accelerating beam through catastrophe theory. Moreover, an experimental scheme based on a digital micromirror device (DMD) with the binary spectral hologram is proposed to generate the target beam by precise modulation, and a longitudinal needle-like focus is observed around the focal region. The experimental results confirm the peculiar features presented in the theoretical findings. Further, the APPB is verified to exhibit self-healing property during propagation with either obstructed cusp or spot intensity maxima point reconstructing after a certain distance. Hence, we believe that the APPB will facilitate the applications in the areas of particle manipulation, material processing and optofludics.

Clinical study on Yishen Qufeng Shengshi Recipe () for glomerular proteinuria patients: A randomized controlled trial.

OBJECTIVE: To explore the therapeutic effect of Yishen Qufeng Shengshi Recipe (, YQSR) in patients with glomerular proteinuria METHODS: A total of 145 patients with glomerular proteinuria were selected and randomly assigned to the treatment group (108 cases) and the control group (37 cases) according to a random number table in a ratio of 3:1. All patients received conventional and symptomatic treatment. In addition, patients in the treatment and control groups were given YQSR (200 mL, twice per day, orally) and losartan (50 mg/d orally), respectively for 6 months. The 24-h urine protein quantity, blood urea nitrogen, and serum creatinine in the two groups were measured at multiple time points before and after treatment. RESULTS: At the end of the study, 5 cases were lost to follow-up in the treatment group and 1 in the control group. Finally, the statistical data included 103 cases in the treatment group and 36 cases in the control group. The total effectiveness after 2, 4, and 6 months was 81.6% (84/103), 87.4% (90/103), and 92.2% (95/103), respectively, in the treatment group and 47.2% (17/36), 55.6% (20/36), and 61.1% (22/36), respectively, in the control group, with significant difference between the two groups (P<0.01 at all observation points). In the treatment group, the curative effect after 6 months was better than that after 2 months (P<0.05). The 24-h urine protein quantity was significantly lower in the treatment group at 3, 4, 5, and 6 months than that in the control group (P<0.05 or P<0.01, respectively) CONCLUSION: YQSR could significantly reduce the amount of glomerular proteinuria in the early stage.

Berberine prevents the apoptosis of mouse podocytes induced by TRAF5 overexpression by suppressing NF-κB activation.

Berberine (BBR) has previously been found to exert beneficial effects on renal injury in experimental rats. However, the mechanisms underlying these effects are not yet fully understood. Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) has been demonstrated to mediate the activation of nuclear factor-κB (NF-κB), which has been implicated in the pathogenesis of chronic kidney disease (CKD). The aim of this study was to investigate the effects of BBR on kidney injury and the activation of the NF-κB signaling pathway in mouse podocytes. TRAF5 was found to be overexpressed in patients with CKD and chronic renal failure (CRF) (data obtained from the dataset GSE48944, as well as from patients at Shuguang Hospital). TRAF5 overexpression significantly inhibited cell viability and induced the apoptosis of mouse podocytes. However, BBR prevented the decrease in cell viability and the apoptosis induced by TRAF5 overexpression. The NF-κB inhibitor, caffeic acid phenethyl ester (CAPE), mimicked the protective effects of BBR, as evidenced by the increased expression of nephrin and podocin, and the decreased the expression of caspase-3 and the ratio of Bax/Bcl-2. Moreover, BBR prevented the decrease in cell viability decrease and the apoptosis induced by TNF-α, interleukin (IL)-6 and lipopolysaccharide (LPS). Taken together, our data indicate that BBR exerts protective effects against CRF partly through the TRAF5-mediated activation of the NF-κB signaling pathway in mouse podocytes.

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

[Effects of Gubentongluo Formula on Oxidative Stress Reflected by Expressions of PPARα and L-FABP in Mice with IgA Nephropathy].

OBJECTIVES: To determine the underlying mechanism of Gubentongluo Formula in the treatment of IgA nephropathy (IgAN). METHODS: C57BL/6 mice were randomly divided into four groups: normal group (n =10), IgAN group (n =10), control group (n =10) and treatment group (n =10). Mice in the normal and IgAN groups were intragastricly administered with normal saline for 12 weeks; while those in the control and treatment groups were given fenofibrate [30 mg/(kg!$d) and Gubentongluo Formula [1.67 mL/(g!$d)], respectively. Urinary albumin was detected at week 0 and 12. At week 12, protein expressions of peroxisome proliferstor activated receptor α (PPARα), liver fatty acid-binding proteins (L-FABP), 4-hydroxy-2-nonenal (4-HNE), and hemeoxygenase-1(HO-1) in renal tissues were determined by Western blot; mRNA expressions of PPARα and L-FABP in renal tissues were determined by florescent quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: At week 12, higher levels of urinary albumin, pathological injuries in glomerular mesangial area, and lower expressions of protein and mRNA of PPARα and L-FABP were found in mice in the IgAN group compared with those in the normal group (P <0.01). The levels of those indicators decreased in those treated with fenofibrate and Gubentongluo Formule, but still higher than the normal controls (P <0.01). The mice treated with Gubentongluo Formula had more significant improvement than those treated with fenofibrate (P <0.05). CONCLUSION: [CM(155.3mm]Gubentongluo formula can improve proteinuria and pathological injuries in glomerular mesangial area of IgAN mice, due to reduction of oxidative stress in renal tissues through regulating the expressions of PPARα and L-FABP.

[Effect of Kangxianling Recipe on p38MAPK/NF-KBp65 Mediated Inflammatory Factors in 5/6 Nephrectomized Mice].

Objective To observe effects of Kangxianling Recipe ( KXLR) on p38MAPK/NF- κBp65 mediated inflammatory factors in chronic renal failure ( CRF) model mice. Methods Totally 56 C57BL/6J male mice (18 -22 g) were recruited in this experiment. Ten were randomly selected as a sham-operation group. The rest 46 mice were used for preparing CRF model by 5/6 nephrectomization. To- tally 33 successfully modeled mice were divided into the model group, the rapamycin (RAP) group, and the KXLR group according to serum creatinine (SCr) level, 11 in each group. Mice in the RAP group were administered with rapamycin (0.13 mg/100 g per day, 0. 5 mL each time) by gastrogavage. Mice in the KXLR group were administered with KXLR (2 g/100 g per day, 0. 5 mL each time) by gastrogavage. Equal volume of distilled water was administered to mice in the model group and the sham-operation group. Mice were sacrificed after 8 weeks of consecutive medication. The expression of neutrophils was ob- served using immunohistochemical assay. Expression levels of p38MAPK/NF-κB p65 protein and TNF-α/ IL-6 mRNA were detected by Western blot and Real-time PCR. Results Compared with the sham-opera- tion group, the number of positive neutrophils increased, expression levels of p38MAPK/NF-κB p65 protein and TNF-α/IL-6 mRNA were enhanced significantly in the model group (P <0. 05, P <0. 01). Com- pared with the model group, the number of neutrophils was reduced, expression levels of p38MAPK/NF- κB p65 protein and TNF-α/IL-6 mRNA were decreased significantly in the KXLR group and the RAP group (P <0. 05, P <0. 01). RAP showed better effect in decreasing p38MAPK protein expression than KXLR (P <0. 05). There was no statistical difference in the rest indices between the KXLR group and the RAP group (P >0. 05). Conclusions KXLR participated the regulation of p38MAPK/NF-κB p65 mediated in- flammation factors. It had certain improvement in renal fibrosis induced renal failure.

[Effect of "Gubentongluo Formula" on the IgA Class Switch Recombination of B Lymohocytes in Peyer's Patches in Mice with IgA Nephropathy].

OBJECTIVE: To explore the underlying mechanism of "Gubentongluo Formula" in treatment of IgA nephropathy (IgAN). METHODS: After the IgAN model was successfully induced at week 12, the Kunming mice were randomly divided into three groups: normal control group (n = 15), IgAN group (n = 15) and Traditional Chinese Medicine (TCM) group. The mice in normal control and IgAN group were intragastriclly administrated with normal saline for 8 weeks; meanwhile, the mice in TCM group were intragastriclly administrated with "Gubentongluo Formula" 1.35 mL/ (g · d). The levels of 24 h urine protein were determined at Week 0, 12 and 20. At week 20, the changes of renal pathology were detected; the mRNA expressions of transforming growth factor-ß (TGF-ß) and small mothers against decapentaplegic (Smad) 3 in Peyer's patches (PPs) were detected by fuorescent quantitative reverse transcription-polymerase chain reaction; the protein expressions of TGF-ß and Smad 3 in PPs were detected by immunohistochemistry technique; the levels of (IgA + B)/B lymphocytes in PPs were determined by flow cytometry. RESULTS: Compared with those results of normal control group, the levels of 24 h urine protein, IgA deposition in glomerular mesangial area, and expressions of protein and mRNA of TGF-ß and Smad3 in IgAN group were significantly increased (P < 0.01). Besides, the levels of (IgA+B)/B lymphocytes were significantly elevated in IgAN group (P < 0.01). All these indicators were improved in TCM group. Compared with IgAN group, the differences were statistically significant (P < 0.01). Compared with those results of control group, the levels of (IgA + B)/B lymphocytes showed no significant difference in TCM group (P > 0.05), but other indicators showed significant differences (P < 0.01). CONCLUSION: "Gubentongluo Formula" could effectively improve proteinuria and suppress IgA deposition in glomerular mesangial area in IgAN mice, due to affect IgA class switch recombination of B lymphocytes in PPs through regulating TGF-ß/Smad3 pathway.

Prevalence, awareness, and treatment of anemia in Chinese patients with nondialysis chronic kidney disease: First multicenter, cross-sectional study.

This was the first multicenter, cross-sectional survey to assess the prevalence of anemia, patient awareness, and treatment status in China. Data of patients with chronic kidney disease (CKD; age, 18-75 years; both out- and inpatients) from 25 hospitals in Shanghai, seeking medical treatment at the nephrology department, were collected between July 1, 2012 and August 31, 2012. The prevalence, awareness, and treatment of anemia in patients with nondialysis CKD (ND-CKD) were assessed. Anemia was defined as serum hemoglobin (Hb) levels ≤12 g/dL in women and ≤13 g/dL in men. A total of 2420 patients with ND-CKD were included. Anemia was established in 1246 (51.5%) patients: 639 (51.3%) men and 607 (48.7%) women. The prevalence of anemia increased with advancing CKD stage (χtrend = 675.14, P < 0.001). Anemia was more prevalent in patients with diabetic nephropathy (68.0%) than in patients with hypertensive renal damage (56.6%) or chronic glomerulonephritis (46.1%, both P < 0.001). Only 39.8% of the anemic patients received treatment with erythropoietin and 27.1% patients received iron products; furthermore, 22.7% of the patients started receiving treatment when their Hb level reached 7 g/dL. The target-achieving rate (Hb at 11-12 g/dL) was only 8.2%. Of the 1246 anemia patients, only 7.5% received more effective and recommended intravenous supplementation. Anemia is highly prevalent in patients with ND-CKD in China, with a low target-achieving rate and poor treatment patterns. The study highlights the need to improve multiple aspects of CKD management to delay the progression of renal failure.

A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy.

Objective. The purpose of this systematic review is to evaluate the evidence of Yiqi Yangyin Huoxue Method for diabetic nephropathy. Methods. 11 electronic databases, through September 2015, were searched to identify randomized controlled trials of Yiqi Yangyin Huoxue Method for diabetic nephropathy. The quality of the included trials was assessed using the Jadad scale. Results. 26 randomized controlled trials were included in our review. Of all the included trials, most of them were considered as high quality. The aggregated results suggested that Yiqi Yangyin Huoxue Method is beneficial to diabetic nephropathy in bringing down the microalbuminuria (SMD = -0.98, 95% CI -1.22 to -0.74), serum creatinine (SMD = -0.56, 95% CI -0.93 to -0.20), beta-2 microglobulin (MD = 0.06, 95% CI 0.01 to 0.12), fasting plasma glucose (MD = -0.35, 95% CI -0.62 to -0.08), and 2-hour postprandial blood glucose (MD = 1.13, 95% CI 0.07 to 2.20), but not in decreasing blood urea nitrogen (SMD = -0.72, 95% CI -1.47 to 0.02) or 2-hour postprandial blood glucose (SMD = -0.48, 95% CI -1.01 to 0.04). Conclusions. Yiqi Yangyin Huoxue Method should be a valid complementary and alternative therapy in the management of diabetic nephropathy, especially in improving UAER, serum creatinine, fasting blood glucose, and beta-2 microglobulin. However, more studies with long follow-up are warrant to confirm the current findings.

Interventional mechanisms of herbs or herbal extracts on renal interstitial fibrosis.

Renal interstitial fibrosis (RIF) is a common development in chronic renal diseases that can lead to uremia and be life-threatening. The RIF pathology has complicated extracellular and intercellular mechanisms, involving many cells and cytokines, resulting in an incomplete mechanistic understanding of the disease. Finding effective herbs or herbal extracts for prevention and treatment of RIF is crucial because current medical approaches do not reliably slow or reverse RIF. In recent years, many experts have worked to identify herbs or herbal extracts to combat RIF both in vivo and in vitro, with some success. This review attempts to summarize the possible interventional mechanisms of herbs or herbal extracts involved in protecting and reversing RIF. The authors found some herbs and their extracts that may ameliorate renal impairments through anti-inflammation, anti-fibrogenesis and stabilization of extra cellular matrix. Among them, tetramethylpyrazine/ligustrazine, curcumin and polyglucoside of Tripterygium have experimentally shown good potential for improving RIF. However, conclusive evidence is still needed, especially in randomized controlled clinical trials. We expect that herbs or herbal extracts will play an important role in RIF treatment and reversal in the future.

Histone deacetylase inhibitors attenuate P-aIgA1-induced cell proliferation and extracellular matrix synthesis in human renal mesangial cells in vitro.

AIM: Aberrantly glycosylated IgA1 is a key factor in the pathogenesis of IgA nephropathy (IgAN). In this study we investigated the effects of aggregated IgA1 derived from IgAN patients (P-aIgA1) on human renal mesangial cells (HMCs) and the anti-proliferative and antifibrotic effects of histone deacetylase (HDAC) inhibitors in vitro. METHODS: Three types of IgA1 were prepared, ie, N-IgA1 (IgA1 from healthy volunteers), P-IgA1 (IgA1 from IgAN patients), and P-aIgA1 (aggregated IgA1 from IgAN patients). The isolated IgA1 was heated for thermal polymerization. The proliferation of human renal mesangial cells (HMCs) were assessed using MTT assay. The expression levels of relevant proteins were examined using immunoblotting assays or immunohistochemistry. RESULTS: P-aIgA1 (25-250 µg/mL) dose-dependently promoted the proliferation of HMCs, and markedly increased the protein levels of type I histone deacetylase (HDAC1, HDAC2 and HDAC8) in the cells. Both P-IgA1 and N-IgA1 were much weaker in stimulating cell proliferation and HDAC expression. P-aIgA1 (50 µg/mL) markedly increased the protein levels of Col1a1 and PAI-1, as well as pSmad2/3 and pStat3 in the cells. Pretreatment with the HDAC inhibitor trichostatin A (TSA, 250 nmol/L) or valproic acid (VPA, 400 µg/mL) partially reversed P-aIgA1-induced cell proliferation and extracellular matrix synthesis in HMCs. CONCLUSION: P-aIgA1 produces pro-proliferative and profibrotic actions in HMCs via upregulating the expression of HDACs, and subsequently activating TGF-ß/Smad2/3 and Jak2/Stat3 signaling pathways. Both VPA and TSA attenuate P-aIgA1-induced cell proliferation and fibrosis in HMCs.

A Clinical Multicenter Randomized Controlled Study on JianpiQinghua Decoction in Treating Stage 3 Chronic Kidney Disease with A Syndrome Type of Dampness-heat due to Spleen Deficiency.

Objective To evaluate the clinical effectiveness of JianpiQinghua decoction in treating stage 3 chronic kidney disease (CKD3) with syndrome type of dampness-heat due to spleen deficiency. Methods A multicenter, randomized, controlled, prospective, double-blind, and double-simulation study was undertaken. A total of 270 CKD3 patients with syndrome type of dampness-heat due to spleen deficiency from the outpatient departments of six general hospitals were randomly divided into telmisartan+analog traditional Chinese medicine (TA) group, traditional Chinese medicine+analog telmisartan (TCMA) group, and telmisartan+traditional Chinese medicine (TTCM) group, in which the corresponding treatment was applied in addition to basic treatment. Six months later, changes in the traditional Chinese medicine (TCM) clinical symptom scores and renal functions before and after treatment were compared among these three groups. Results Of these 270 CKD3 patients who had been enrolled in this study, 30 cases lost to follow-up. The baseline data were comparable among these three groups. After treatment, the TCM clinical symptom scores of both syndrome of spleen-qi deficiency and dampness-heat in TA group were significantly higher than those in TCMA group and TTCM group (P<0.001). With the treatment time prolonged, the TCM clinical symptom scores showed similar descending trends in TCMA group and TTCM group but were different from that in TA group. After treatment, abnormal creatinine rate decreased (P=0.003), and these three treatments and their interactions with each visit had no effect on serum urea nitrogen value (P=0.270, P=0.520); with prolonged treatment, the estimated glomerular filtration rates in three groups tended to be relatively stable after the first rise. The liver function and abnormal serum potassium rate were not statistically significant before and after treatment (P>0.05). Conclusions JianpiQinghua decoction can improve clinical symptoms of TCM in CKD3 patients with syndrome type of dampness-heat due to spleen deficiency and thus improve the quality of life and prognosis. The clinical efficacy of JianpiQinghua decoction alone or combined with telmisartan is superior to telmisartan monotherapy.